Simple and Fast Method for Fabrication of Endoscopic Implantable Sensor Arrays

PubMed Central

Tahirbegi, I. Bogachan; Alvira, Margarita; Mir, Mònica; Samitier, Josep

2014-01-01

Here we have developed a simple method for the fabrication of disposable implantable all-solid-state ion-selective electrodes (ISE) in an array format without using complex fabrication equipment or clean room facilities. The electrodes were designed in a needle shape instead of planar electrodes for a full contact with the tissue. The needle-shape platform comprises 12 metallic pins which were functionalized with conductive inks and ISE membranes. The modified microelectrodes were characterized with cyclic voltammetry, scanning electron microscope (SEM), and optical interferometry. The surface area and roughness factor of each microelectrode were determined and reproducible values were obtained for all the microelectrodes on the array. In this work, the microelectrodes were modified with membranes for the detection of pH and nitrate ions to prove the reliability of the fabricated sensor array platform adapted to an endoscope. PMID:24971473

Chronic In Vivo Stability Assessment of Carbon Fiber Microelectrode Arrays

PubMed Central

Patel, Paras R.; Zhang, Huanan; Robbins, Matthew T.; Nofar, Justin B.; Marshall, Shaun P.; Kobylarek, Michael J.; Kozai, Takashi D. Y.; Kotov, Nicholas A.; Chestek, Cynthia A.

2016-01-01

Objective Individual carbon fiber microelectrodes can record unit activity in both acute and semi-chronic (∼1 month) implants. Additionally, new methods have been developed to insert a 16 channel array of carbon fiber microelectrodes. Before assessing the in vivo long-term viability of these arrays, accelerated soak tests were carried out to determine the most stable site coating material. Next, a multi-animal, multi-month, chronic implantation study was carried out with carbon fiber microelectrode arrays and silicon electrodes. Approach Carbon fibers were first functionalized with one of two different formulations of PEDOT and subjected to accelerated aging in a heated water bath. After determining the best PEDOT formula to use, carbon fiber arrays were chronically implanted in rat motor cortex. Some rodents were also implanted with a single silicon electrode, while others received both. At the end of the study a subset of animals were perfused and the brain tissue sliced. Tissue sections were stained for astrocytes, microglia, and neurons. The local reactive responses were assessed using qualitative and quantitative methods. Main results Electrophysiology recordings showed the carbon fibers detecting unit activity for at least 3 months with average amplitudes of ∼200 μV. Histology analysis showed the carbon fiber arrays with a minimal to non-existent glial scarring response with no adverse effects on neuronal density. Silicon electrodes showed large glial scarring that impacted neuronal counts. Significance This study has validated the use of carbon fiber microelectrode arrays as a chronic neural recording technology. These electrodes have demonstrated the ability to detect single units with high amplitude over 3 months, and show the potential to record for even longer periods. In addition, the minimal reactive response should hold stable indefinitely, as any response by the immune system may reach a steady state after 12 weeks. PMID:27705958

Chronic in vivo stability assessment of carbon fiber microelectrode arrays

NASA Astrophysics Data System (ADS)

Patel, Paras R.; Zhang, Huanan; Robbins, Matthew T.; Nofar, Justin B.; Marshall, Shaun P.; Kobylarek, Michael J.; Kozai, Takashi D. Y.; Kotov, Nicholas A.; Chestek, Cynthia A.

2016-12-01

Objective. Individual carbon fiber microelectrodes can record unit activity in both acute and semi-chronic (∼1 month) implants. Additionally, new methods have been developed to insert a 16 channel array of carbon fiber microelectrodes. Before assessing the in vivo long-term viability of these arrays, accelerated soak tests were carried out to determine the most stable site coating material. Next, a multi-animal, multi-month, chronic implantation study was carried out with carbon fiber microelectrode arrays and silicon electrodes. Approach. Carbon fibers were first functionalized with one of two different formulations of PEDOT and subjected to accelerated aging in a heated water bath. After determining the best PEDOT formula to use, carbon fiber arrays were chronically implanted in rat motor cortex. Some rodents were also implanted with a single silicon electrode, while others received both. At the end of the study a subset of animals were perfused and the brain tissue sliced. Tissue sections were stained for astrocytes, microglia, and neurons. The local reactive responses were assessed using qualitative and quantitative methods. Main results. Electrophysiology recordings showed the carbon fibers detecting unit activity for at least 3 months with average amplitudes of ∼200 μV. Histology analysis showed the carbon fiber arrays with a minimal to non-existent glial scarring response with no adverse effects on neuronal density. Silicon electrodes showed large glial scarring that impacted neuronal counts. Significance. This study has validated the use of carbon fiber microelectrode arrays as a chronic neural recording technology. These electrodes have demonstrated the ability to detect single units with high amplitude over 3 months, and show the potential to record for even longer periods. In addition, the minimal reactive response should hold stable indefinitely, as any response by the immune system may reach a steady state after 12 weeks.

Neural control of cursor trajectory and click by a human with tetraplegia 1000 days after implant of an intracortical microelectrode array

NASA Astrophysics Data System (ADS)

Simeral, J. D.; Kim, S.-P.; Black, M. J.; Donoghue, J. P.; Hochberg, L. R.

2011-04-01

The ongoing pilot clinical trial of the BrainGate neural interface system aims in part to assess the feasibility of using neural activity obtained from a small-scale, chronically implanted, intracortical microelectrode array to provide control signals for a neural prosthesis system. Critical questions include how long implanted microelectrodes will record useful neural signals, how reliably those signals can be acquired and decoded, and how effectively they can be used to control various assistive technologies such as computers and robotic assistive devices, or to enable functional electrical stimulation of paralyzed muscles. Here we examined these questions by assessing neural cursor control and BrainGate system characteristics on five consecutive days 1000 days after implant of a 4 × 4 mm array of 100 microelectrodes in the motor cortex of a human with longstanding tetraplegia subsequent to a brainstem stroke. On each of five prospectively-selected days we performed time-amplitude sorting of neuronal spiking activity, trained a population-based Kalman velocity decoding filter combined with a linear discriminant click state classifier, and then assessed closed-loop point-and-click cursor control. The participant performed both an eight-target center-out task and a random target Fitts metric task which was adapted from a human-computer interaction ISO standard used to quantify performance of computer input devices. The neural interface system was further characterized by daily measurement of electrode impedances, unit waveforms and local field potentials. Across the five days, spiking signals were obtained from 41 of 96 electrodes and were successfully decoded to provide neural cursor point-and-click control with a mean task performance of 91.3% ± 0.1% (mean ± s.d.) correct target acquisition. Results across five consecutive days demonstrate that a neural interface system based on an intracortical microelectrode array can provide repeatable, accurate point-and-click control of a computer interface to an individual with tetraplegia 1000 days after implantation of this sensor.

Neural control of cursor trajectory and click by a human with tetraplegia 1000 days after implant of an intracortical microelectrode array

PubMed Central

Simeral, J D; Kim, S-P; Black, M J; Donoghue, J P; Hochberg, L R

2013-01-01

The ongoing pilot clinical trial of the BrainGate neural interface system aims in part to assess the feasibility of using neural activity obtained from a small-scale, chronically implanted, intracortical microelectrode array to provide control signals for a neural prosthesis system. Critical questions include how long implanted microelectrodes will record useful neural signals, how reliably those signals can be acquired and decoded, and how effectively they can be used to control various assistive technologies such as computers and robotic assistive devices, or to enable functional electrical stimulation of paralyzed muscles. Here we examined these questions by assessing neural cursor control and BrainGate system characteristics on five consecutive days 1000 days after implant of a 4 × 4 mm array of 100 microelectrodes in the motor cortex of a human with longstanding tetraplegia subsequent to a brainstem stroke. On each of five prospectively-selected days we performed time-amplitude sorting of neuronal spiking activity, trained a population-based Kalman velocity decoding filter combined with a linear discriminant click state classifier, and then assessed closed-loop point-and-click cursor control. The participant performed both an eight-target center-out task and a random target Fitts metric task which was adapted from a human-computer interaction ISO standard used to quantify performance of computer input devices. The neural interface system was further characterized by daily measurement of electrode impedances, unit waveforms and local field potentials. Across the five days, spiking signals were obtained from 41 of 96 electrodes and were successfully decoded to provide neural cursor point-and-click control with a mean task performance of 91.3% ± 0.1% (mean ± s.d.) correct target acquisition. Results across five consecutive days demonstrate that a neural interface system based on an intracortical microelectrode array can provide repeatable, accurate point-and-click control of a computer interface to an individual with tetraplegia 1000 days after implantation of this sensor. PMID:21436513

HISTOLOGICAL STUDIES OF THE EFFECTS OF CHRONIC IMPLANTATION OF CERAMIC-BASED MICROELECTRODE ARRAYS AND MICRODIALYSIS PROBES IN RAT PREFRONTAL CORTEX

PubMed Central

Hascup, Erin R.; Bjerkén, Sara af; Hascup, Kevin N.; Pomerleau, Francois; Huettl, Peter; Strömberg, Ingrid; Gerhardt, Greg A.

2010-01-01

Chronic implantation of neurotransmitter measuring devices is essential for awake, behavioral studies occurring over multiple days. Little is known regarding the effects of long term implantation on surrounding brain parenchyma and the resulting alterations in the functional properties of this tissue. We examined the extent of tissue damage produced by chronic implantation of either ceramic microelectrode arrays (MEAs) or microdialysis probes. Histological studies were carried out on fixed tissues using stains for neurons (cresyl violet), astrocytes (GFAP), microglia (Iba-1), glutamatergic nerve fibers (VGLUT1), and the blood-brain barrier (SMI-71). Nissl staining showed pronounced tissue body loss with microdialysis implants compared to MEAs. The MEAs produced mild gliosis extending 50–100 µm from the tracks, with a significant change in the affected areas starting at 3 days. By contrast, the microdialysis probes produced gliosis extending 200–300 µm from the track, which was significant at 3 and 7 days. Markers for microglia and glutamatergic fibers supported that the MEAs produce minimal damage with significant changes occurring only at 3 and 7 days that return to control levels by one month. SMI-71 staining supported integrity of the blood brain barrier out to 1 week for both the microdialysis probes and the MEAs. This data support that the ceramic MEAs small size and biocompatibility are necessary to accurately measure neurotransmitter levels in the intact brain. The minimal invasiveness of the MEAs reduce tissue loss, allowing for long term (>6 month) electrochemical and electrophysiological monitoring of brain activity. PMID:19577548

Chronic tissue response to untethered microelectrode implants in the rat brain and spinal cord

NASA Astrophysics Data System (ADS)

Ersen, Ali; Elkabes, Stella; Freedman, David S.; Sahin, Mesut

2015-02-01

Objective. Microelectrodes implanted in the central nervous system (CNS) often fail in long term implants due to the immunological tissue response caused by tethering forces of the connecting wires. In addition to the tethering effect, there is a mechanical stress that occurs at the device-tissue interface simply because the microelectrode is a rigid body floating in soft tissue and it cannot reshape itself to comply with changes in the surrounding tissue. In the current study we evaluated the scar tissue formation to tetherless devices with two significantly different geometries in the rat brain and spinal cord in order to investigate the effects of device geometry. Approach. One of the implant geometries resembled the wireless, floating microstimulators that we are currently developing in our laboratory and the other was a (shank only) Michigan probe for comparison. Both electrodes were implanted into either the cervical spinal cord or the motor cortices, one on each side. Main results. The most pronounced astroglial and microglial reactions occurred within 20 μm from the device and decreased sharply at larger distances. Both cell types displayed the morphology of non-activated cells past the 100 μm perimeter. Even though the aspect ratios of the implants were different, the astroglial and microglial responses to both microelectrode types were very mild in the brain, stronger and yet limited in the spinal cord. Significance. These observations confirm previous reports and further suggest that tethering may be responsible for most of the tissue response in chronic implants and that the electrode size has a smaller contribution with floating electrodes. The electrode size may be playing primarily an amplifying role to the tethering forces in the brain whereas the size itself may induce chronic response in the spinal cord where the movement of surrounding tissues is more significant.

Seven Years of Recording from Monkey Cortex with a Chronically Implanted Multiple Microelectrode

PubMed Central

Krüger, Jürgen; Caruana, Fausto; Volta, Riccardo Dalla; Rizzolatti, Giacomo

2010-01-01

A brush of 64 microwires was chronically implanted in the ventral premotor cortex of a macaque monkey. Contrary to common approaches, the wires were inserted from the white matter side. This approach, by avoiding mechanical pressure on the dura and pia mater during penetration, disturbed only minimally the cortical recording site. With this approach isolated potentials and multiunit activity were recorded for more than 7 years in about one-third of electrodes. The indirect insertion method also provided an excellent stability within each recording session, and in some cases even allowed recording from the same neurons for several years. Histological examination of the implanted brain region shows only a very marginal damage to the recording area. Advantages and problems related to long-term recording are discussed. PMID:20577628

Feasibility of microelectrode array (MEA) based on silicone-polyimide hybrid for retina prosthesis.

PubMed

Kim, Eui Tae; Kim, Cinoo; Lee, Seung Woo; Seo, Jong-Mo; Chung, Hum; Kim, Sung June

2009-09-01

To adopt micropatterning technology in manufacturing silicone elastomer-based microelectrode arrays for retinal stimulation, a silicone-polyimide hybrid microelectrode array was proposed and tested in vivo. Gold microelectrodes were created by semiconductor manufacturing technology based on polyimide and were hybridized with silicone elastomer by spin coating. The stability of the hybrid between the two materials was flex and blister tested. The feasibility of the hybrid electrode was evaluated in the rabbit eye by reviewing optical coherence tomography (OCT) findings after suprachoroidal implantation. The flex test showed no dehiscence between the two materials for 24 hours of alternative flexion and extension from -45.0 degrees to +45.0 degrees . During the blister test, delamination was observed at 8.33 +/- 1.36 psi of pressure stress; however, this property was improved to 11.50 +/- 1.04 psi by oxygen plasma treatment before hybridization. OCT examination revealed that the implanted electrodes were safely located in the suprachoroidal space during the 4-week follow-up period. The silicone-polyimide hybrid microelectrode array showed moderate physical properties, which are suitable for in vivo application. Appropriate pretreatment before hybridization improved electrode stability. In vivo testing indicated that this electrode is suitable as a stimulation electrode in artificial retina.

The role of flexible polymer interconnects in chronic tissue response induced by intracortical microelectrodes--a modeling and an in vivo study.

PubMed

Subbaroyan, Jeyakumar; Kipke, Daryl R

2006-01-01

Chronic tissue response induced by tethering is one of the major causes for implant failure in intracortical microelectrodes. In this study, we had explored the hypothesis that flexible interconnects could provide strain relief against forces of "micromotion" and hence could result in maintaining a healthy tissue surrounding the implant. Finite element modeling results indicated that flexible interconnects, namely polyimide (E=2 GPa) and polydimethylsiloxane (PDMS, E=6 MPa), reduced the interfacial strain by 66% and two orders of magnitude, respectively. Quantitative immunohistochemistry results indicated that significant neuronal loss occurred up to 60 mum from the implant interface. This was strongly correlated to both glial fibrillary acidic protein (GFAP) expression and simulated strain as a function of distance away from the implant.

Electrical Characterization of 3D Au Microelectrodes for Use in Retinal Prostheses.

PubMed

Lee, Sangmin; Ahn, Jae Hyun; Seo, Jong-Mo; Chung, Hum; Cho, Dong-Il Dan

2015-06-17

In order to provide high-quality visual information to patients who have implanted retinal prosthetic devices, the number of microelectrodes should be large. As the number of microelectrodes is increased, the dimensions of each microelectrode must be decreased, which in turn results in an increased microelectrode interface impedance and decreased injection current dynamic range. In order to improve the trade-off envelope between the number of microelectrodes and the current injection characteristics, a 3D microelectrode structure can be used as an alternative. In this paper, the electrical characteristics of 2D and 3D Au microelectrodes were investigated. In order to examine the effects of the structural difference, 2D and 3D Au microelectrodes with different base areas but similar effective surface areas were fabricated and evaluated. Interface impedances were measured and similar dynamic ranges were obtained for both 2D and 3D Au microelectrodes. These results indicate that more electrodes can be implemented in the same area if 3D designs are used. Furthermore, the 3D Au microelectrodes showed substantially enhanced electrical durability characteristics against over-injected stimulation currents, withstanding electrical currents that are much larger than the limit measured for 2D microelectrodes of similar area. This enhanced electrical durability property of 3D Au microelectrodes is a new finding in microelectrode research, and makes 3D microelectrodes very desirable devices.

Thinking Small – Progress on Microscale Neurostimulation Technology

PubMed Central

Pancrazio, Joseph J.; Deku, Felix; Ghazavi, Atefeh; Stiller, Allison M.; Rihani, Rashed; Frewin, Christopher L.; Varner, Victor D.; Gardner, Timothy J.; Cogan, Stuart F.

2017-01-01

Objectives Neural stimulation is well-accepted as an effective therapy for a wide range of neurological disorders. While the scale of clinical devices is relatively large, translational and pilot clinical applications are underway for microelectrode-based systems. Microelectrodes have the advantage of stimulating a relatively small tissue volume which may improve selectivity of therapeutic stimuli. Current microelectrode technology is associated with chronic tissue response which limits utility of these devices for neural recording and stimulation. One approach for addressing the tissue response problem may be to reduce physical dimensions of the device. “Thinking small” is a trend for the electronics industry, and for implantable neural interfaces, the result may be a device that can evade the foreign body response. Materials and Methods This review paper surveys our current understanding pertaining to the relationship between implant size and tissue response and the state-of-the-art in ultra-small microelectrodes. A comprehensive literature search was performed using PubMed, Web of Science (Clarivate Analytics), and Google Scholar. Results The literature review shows recent efforts to create microelectrodes that are extremely thin appear to reduce or even eliminate the chronic tissue response. With high charge capacity coatings, ultra-microelectrodes fabricated from emerging polymers and amorphous silicon carbide appear promising for neurostimulation applications. Conclusion We envision the emergence of robust and manufacturable ultra-microelectrodes that leverage advanced materials where the small cross-sectional geometry enables compliance within tissue. Nevertheless, future testing under in vivo conditions is particularly important for assessing the stability of thin film devices under chronic stimulation. PMID:29076214

Simultaneous recording of brain extracellular glucose, spike and local field potential in real time using an implantable microelectrode array with nano-materials

NASA Astrophysics Data System (ADS)

Wei, Wenjing; Song, Yilin; Fan, Xinyi; Zhang, Song; Wang, Li; Xu, Shengwei; Wang, Mixia; Cai, Xinxia

2016-03-01

Glucose is the main substrate for neurons in the central nervous system. In order to efficiently characterize the brain glucose mechanism, it is desirable to determine the extracellular glucose dynamics as well as the corresponding neuroelectrical activity in vivo. In the present study, we fabricated an implantable microelectrode array (MEA) probe composed of platinum electrochemical and electrophysiology microelectrodes by standard micro electromechanical system (MEMS) processes. The MEA probe was modified with nano-materials and implanted in a urethane-anesthetized rat for simultaneous recording of striatal extracellular glucose, local field potential (LFP) and spike on the same spatiotemporal scale when the rat was in normoglycemia, hypoglycemia and hyperglycemia. During these dual-mode recordings, we observed that increase of extracellular glucose enhanced the LFP power and spike firing rate, while decrease of glucose had an opposite effect. This dual mode MEA probe is capable of examining specific spatiotemporal relationships between electrical and chemical signaling in the brain, which will contribute significantly to improve our understanding of the neuron physiology.

A novel flexible cuff-like microelectrode for dual purpose, acute and chronic electrical interfacing with the mouse cervical vagus nerve

NASA Astrophysics Data System (ADS)

Caravaca, A. S.; Tsaava, T.; Goldman, L.; Silverman, H.; Riggott, G.; Chavan, S. S.; Bouton, C.; Tracey, K. J.; Desimone, R.; Boyden, E. S.; Sohal, H. S.; Olofsson, P. S.

2017-12-01

Objective. Neural reflexes regulate immune responses and homeostasis. Advances in bioelectronic medicine indicate that electrical stimulation of the vagus nerve can be used to treat inflammatory disease, yet the understanding of neural signals that regulate inflammation is incomplete. Current interfaces with the vagus nerve do not permit effective chronic stimulation or recording in mouse models, which is vital to studying the molecular and neurophysiological mechanisms that control inflammation homeostasis in health and disease. We developed an implantable, dual purpose, multi-channel, flexible ‘microelectrode’ array, for recording and stimulation of the mouse vagus nerve. Approach. The array was microfabricated on an 8 µm layer of highly biocompatible parylene configured with 16 sites. The microelectrode was evaluated by studying the recording and stimulation performance. Mice were chronically implanted with devices for up to 12 weeks. Main results. Using the microelectrode in vivo, high fidelity signals were recorded during physiological challenges (e.g potassium chloride and interleukin-1β), and electrical stimulation of the vagus nerve produced the expected significant reduction of blood levels of tumor necrosis factor (TNF) in endotoxemia. Inflammatory cell infiltration at the microelectrode 12 weeks of implantation was limited according to radial distribution analysis of inflammatory cells. Significance. This novel device provides an important step towards a viable chronic interface for cervical vagus nerve stimulation and recording in mice.

Single neuronal recordings using surface micromachined polysilicon microelectrodes.

PubMed

Muthuswamy, Jit; Okandan, Murat; Jackson, Nathan

2005-03-15

Bulk micromachining techniques of silicon have been used successfully in the past several years to microfabricate microelectrodes for monitoring single neurons in acute and chronic experiments. In this study we report for the first time a novel surface micromachining technique to microfabricate a very thin polysilicon microelectrode that can be used for monitoring single-unit activity in the central nervous system. The microelectrodes are 3 mm long and 50 microm x 3.75 microm in cross-section. Excellent signal to noise ratios in the order of 25-35 dB were obtained while recording neuronal action potentials. The microelectrodes successfully penetrated the brains after a microincision of the dura mater. Chronic implantation of the microprobe for up to 33 days produced only minor gliosis. Since the polysilicon shank acts as a conductor, additional processing steps involved in laying conductor lines on silicon substrates are avoided. Further, surface micromachining allows for fabricating extremely thin microelectrodes which could result in decreased inflammatory responses. We conclude that the polysilicon microelectrode reported here could be a complementary approach to bulk-micromachined silicon microelectrodes for chronic monitoring of single neurons in the central nervous system.

Implantable liquid metal-based flexible neural microelectrode array and its application in recovering animal locomotion functions

NASA Astrophysics Data System (ADS)

Guo, Rui; Liu, Jing

2017-10-01

With significant advantages in rapidly restoring the nerve function, electrical stimulation of nervous tissue is a crucial treatment of peripheral nerve injuries leading to common movement disorder. However, the currently available stimulating electrodes generally based on rigid conductive materials would cause a potential mechanical mismatch with soft neural tissues which thus reduces long-term effects of electrical stimulation. Here, we proposed and fabricated a flexible neural microelectrode array system based on the liquid metal GaIn alloy (75.5% Ga and 24.5% In by weight) and via printing approach. Such an alloy with a unique low melting point (10.35 °C) owns excellent electrical conductivity and high compliance, which are beneficial to serve as implantable flexible neural electrodes. The flexible neural microelectrode array embeds four liquid metal electrodes and stretchable interconnects in a PDMS membrane (500 µm in thickness) that possess a lower elastic modulus (1.055 MPa), which is similar to neural tissues with elastic moduli in the 0.1-1.5 MPa range. The electrical experiments indicate that the liquid metal interconnects could sustain over 7000 mechanical stretch cycles with resistance approximately staying at 4 Ω. Over the conceptual experiments on animal sciatic nerve electrical stimulation, the dead bullfrog implanted with flexible neural microelectrode array could even rhythmically contract and move its lower limbs under the electrical stimulations from the implant. This demonstrates a highly efficient way for quickly recovering biological nerve functions. Further, the good biocompatibility of the liquid metal material was justified via a series of biological experiments. This liquid metal modality for neural stimulation is expected to play important roles as biologic electrodes to overcome the fundamental mismatch in mechanics between biological tissues and electronic devices in the coming time.

Spatial and temporal characteristics of V1 microstimulation during chronic implantation of a microelectrode array in a behaving macaque

NASA Astrophysics Data System (ADS)

Davis, T. S.; Parker, R. A.; House, P. A.; Bagley, E.; Wendelken, S.; Normann, R. A.; Greger, B.

2012-12-01

Objective. It has been hypothesized that a vision prosthesis capable of evoking useful visual percepts can be based upon electrically stimulating the primary visual cortex (V1) of a blind human subject via penetrating microelectrode arrays. As a continuation of earlier work, we examined several spatial and temporal characteristics of V1 microstimulation. Approach. An array of 100 penetrating microelectrodes was chronically implanted in V1 of a behaving macaque monkey. Microstimulation thresholds were measured using a two-alternative forced choice detection task. Relative locations of electrically-evoked percepts were measured using a memory saccade-to-target task. Main results. The principal finding was that two years after implantation we were able to evoke behavioural responses to electric stimulation across the spatial extent of the array using groups of contiguous electrodes. Consistent responses to stimulation were evoked at an average threshold current per electrode of 204 ± 49 µA (mean ± std) for groups of four electrodes and 91 ± 25 µA for groups of nine electrodes. Saccades to electrically-evoked percepts using groups of nine electrodes showed that the animal could discriminate spatially distinct percepts with groups having an average separation of 1.6 ± 0.3 mm (mean ± std) in cortex and 1.0° ± 0.2° in visual space. Significance. These results demonstrate chronic perceptual functionality and provide evidence for the feasibility of a cortically-based vision prosthesis for the blind using penetrating microelectrodes.

Fabrication of implantable microelectrode arrays by laser cutting of silicone rubber and platinum foil.

PubMed

Schuettler, M; Stiess, S; King, B V; Suaning, G J

2005-03-01

A new method for fabrication of microelectrode arrays comprised of traditional implant materials is presented. The main construction principle is the use of spun-on medical grade silicone rubber as insulating substrate material and platinum foil as conductor (tracks, pads and electrodes). The silicone rubber and the platinum foil are patterned by laser cutting using an Nd:YAG laser and a microcontroller-driven, stepper-motor operated x-y table. The method does not require expensive clean room facilities and offers an extremely short design-to-prototype time of below 1 day. First prototypes demonstrate a minimal achievable feature size of about 30 microm.

Concurrent electrophysiology and TPM/OCT imaging of long-term implanted electrodes (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hammer, Daniel X.; Gao, Yu-Rong; Ye, Meijun; Welle, Cristin G.

2017-02-01

Microelectrodes implanted in the brain cause mechanical damage to the tissue that mediate neuroinflammation and eventual encapsulation by microglia and astrocytes. Electrophysiological signals recorded from implants used in brain-computer interfaces (BCI) degrade over time, limiting their usefulness, but the precise causes and progression are not fully understood. We are investigating the dynamics of brain morphological changes and neuroinflammation with a multimodal approach to better understand the potential causes of implant failure. We performed weekly optical coherence tomography (OCT)-guided two-photon microscopy (TPM) in the region around microelectrodes inserted under a cranial window concurrent with electrophysiological recordings. Transgenic mouse cohorts studied include Thy1-YFP, Cx3cr1, and GFAP-GFP to image neurons, microglia, and astrocytes, respectively. Single-shank, 16-channel, Michigan-style microelectrodes were inserted under the window at a 15-20° angle with an insertion depth up to cortical layer 5. Single-unit and local field potential (LFP) recordings were collected for 15 minutes while the animals moved freely in their home cages. Cellular and vascular morphology were monitored using TPM and OCT at timepoints matched to the recordings. In preliminary data, we observed a decay of neural firing rates in most of the channels after implantation. The relationship between electrophysiological measures (e.g., neural firing rate, LFP power) and neural/vascular morphological measurements (e.g., cell density, glial migration, blood flow changes) will be quantified. The multimodal approach combining electrophysiology and optical imaging provides a broader picture of the multifactorial nature of the response to implanted electrodes. Understanding and accounting for the response may lead to better BCI designs and approaches.

Thinking Small: Progress on Microscale Neurostimulation Technology.

PubMed

Pancrazio, Joseph J; Deku, Felix; Ghazavi, Atefeh; Stiller, Allison M; Rihani, Rashed; Frewin, Christopher L; Varner, Victor D; Gardner, Timothy J; Cogan, Stuart F

2017-12-01

Neural stimulation is well-accepted as an effective therapy for a wide range of neurological disorders. While the scale of clinical devices is relatively large, translational, and pilot clinical applications are underway for microelectrode-based systems. Microelectrodes have the advantage of stimulating a relatively small tissue volume which may improve selectivity of therapeutic stimuli. Current microelectrode technology is associated with chronic tissue response which limits utility of these devices for neural recording and stimulation. One approach for addressing the tissue response problem may be to reduce physical dimensions of the device. "Thinking small" is a trend for the electronics industry, and for implantable neural interfaces, the result may be a device that can evade the foreign body response. This review paper surveys our current understanding pertaining to the relationship between implant size and tissue response and the state-of-the-art in ultrasmall microelectrodes. A comprehensive literature search was performed using PubMed, Web of Science (Clarivate Analytics), and Google Scholar. The literature review shows recent efforts to create microelectrodes that are extremely thin appear to reduce or even eliminate the chronic tissue response. With high charge capacity coatings, ultramicroelectrodes fabricated from emerging polymers, and amorphous silicon carbide appear promising for neurostimulation applications. We envision the emergence of robust and manufacturable ultramicroelectrodes that leverage advanced materials where the small cross-sectional geometry enables compliance within tissue. Nevertheless, future testing under in vivo conditions is particularly important for assessing the stability of thin film devices under chronic stimulation. © 2017 International Neuromodulation Society.

Silicon/SU8 multi-electrode micro-needle for in vivo neurochemical monitoring.

PubMed

Vasylieva, Natalia; Marinesco, Stéphane; Barbier, Daniel; Sabac, Andrei

2015-10-15

Simultaneous monitoring of glucose and lactate is an important challenge for understanding brain energetics in physiological or pathological states. We demonstrate here a versatile method based on a minimally invasive single implantation in the rat brain. A silicon/SU8-polymer multi-sensing needle-shaped biosensor, was fabricated and tested. The multi-electrode array design comprises three platinum planar microelectrodes with a surface area of 40 × 200 µm(2) and a spacing of 200 µm, which were micromachined on a single 3mm long micro-needle having a 100 × 50 µm(2) cross-section for reduced tissue damage during implantation. Platinum micro-electrodes were aligned at the bottom of micro-wells obtained by photolithography on a SU8 photoresist layer. After clean room processing, each micro-electrode was functionalized inside the micro-wells by means of a micro-dispensing device, either with glucose oxidase or with lactate oxidase, which were cross-linked on the platinum electrodes. The third electrode covered with Bovine Serum Albumin (BSA) was used for the control of non-specific currents. The thick SU8 photoresist layer has revealed excellent electrical insulation of the micro-electrodes and between interconnection lines, and ensured a precise localization and packaging of the sensing enzymes on platinum micro-electrodes. During in vitro calibration with concentrations of analytes in the mM range, the micro-wells patterned in the SU8 photoresist proved to be highly effective in eliminating cross-talk signals, caused by H2O2 diffusion from closely spaced micro-electrodes. Moreover, our biosensor was successfully assayed in the rat cortex for simultaneous monitoring of both glucose and lactate during insulin and glucose administration. Copyright © 2015 Elsevier B.V. All rights reserved.

Fabrication and testing of polyimide-based microelectrode arrays for cortical mapping of evoked potentials.

PubMed

Myllymaa, Sami; Myllymaa, Katja; Korhonen, Hannu; Töyräs, Juha; Jääskeläinen, Juha E; Djupsund, Kaj; Tanila, Heikki; Lappalainen, Reijo

2009-06-15

Modern microfabrication techniques make it possible to develop microelectrode arrays that may be utilized not only in neurophysiological research but also in the clinic, e.g. in neurosurgery and as elements of neural prostheses. The aim of this study was to test whether a flexible microelectrode array is suitable for recording cortical surface field potentials in rats. Polyimide-based microelectrode arrays were fabricated by utilizing microfabrication techniques e.g. photolithography and magnetron sputter deposition. The present microelectrode array consists of eight platinum microelectrodes (round-shaped, Ø: 200 microm), transmission lines and connector pads sandwiched between two thin layers of biocompatible polyimide. The microelectrode arrays were electrochemically characterized by impedance spectroscopy in physiological saline solution and successfully tested in vivo by conducting acute and chronic measurements of evoked potentials on the surface of rat cortex. The arrays proved excellent flexibility and mechanical strength during handling and implantation onto the surface of cortex. The excellent electrochemical characteristics and stable in vivo recordings with high spatiotemporal resolution highlight the potential of these arrays. The fabrication protocol described here allows implementation of several other neural interfaces with different layouts, material selections or target areas either for recording or stimulation purposes.

A Multimodal, SU-8 - Platinum - Polyimide Microelectrode Array for Chronic In Vivo Neurophysiology

PubMed Central

Márton, Gergely; Orbán, Gábor; Kiss, Marcell; Fiáth, Richárd; Pongrácz, Anita; Ulbert, István

2015-01-01

Utilization of polymers as insulator and bulk materials of microelectrode arrays (MEAs) makes the realization of flexible, biocompatible sensors possible, which are suitable for various neurophysiological experiments such as in vivo detection of local field potential changes on the surface of the neocortex or unit activities within the brain tissue. In this paper the microfabrication of a novel, all-flexible, polymer-based MEA is presented. The device consists of a three dimensional sensor configuration with an implantable depth electrode array and brain surface electrodes, allowing the recording of electrocorticographic (ECoG) signals with laminar ones, simultaneously. In vivo recordings were performed in anesthetized rat brain to test the functionality of the device under both acute and chronic conditions. The ECoG electrodes recorded slow-wave thalamocortical oscillations, while the implanted component provided high quality depth recordings. The implants remained viable for detecting action potentials of individual neurons for at least 15 weeks. PMID:26683306

A Multimodal, SU-8 - Platinum - Polyimide Microelectrode Array for Chronic In Vivo Neurophysiology.

PubMed

Márton, Gergely; Orbán, Gábor; Kiss, Marcell; Fiáth, Richárd; Pongrácz, Anita; Ulbert, István

2015-01-01

Utilization of polymers as insulator and bulk materials of microelectrode arrays (MEAs) makes the realization of flexible, biocompatible sensors possible, which are suitable for various neurophysiological experiments such as in vivo detection of local field potential changes on the surface of the neocortex or unit activities within the brain tissue. In this paper the microfabrication of a novel, all-flexible, polymer-based MEA is presented. The device consists of a three dimensional sensor configuration with an implantable depth electrode array and brain surface electrodes, allowing the recording of electrocorticographic (ECoG) signals with laminar ones, simultaneously. In vivo recordings were performed in anesthetized rat brain to test the functionality of the device under both acute and chronic conditions. The ECoG electrodes recorded slow-wave thalamocortical oscillations, while the implanted component provided high quality depth recordings. The implants remained viable for detecting action potentials of individual neurons for at least 15 weeks.

Toward the development of a cortically based visual neuroprosthesis.

PubMed

Normann, Richard A; Greger, Bradley; Greger, Bradley A; House, Paul; Romero, Samuel F; Pelayo, Francisco; Fernandez, Eduardo

2009-06-01

Motivated by the success of cochlear implants for deaf patients, we are now facing the goal of creating a visual neuroprosthesis designed to interface with the occipital cortex as a means through which a limited but useful sense of vision could be restored in profoundly blind patients. We review the most important challenges regarding this neuroprosthetic approach and emphasize the need for basic human psychophysical research on the best way of presenting complex stimulating patterns through multiple microelectrodes. Continued research will hopefully lead to the development of and design specifications for the first generation of a cortically based visual prosthesis system.

PERSPECTIVE: Toward the development of a cortically based visual neuroprosthesis

NASA Astrophysics Data System (ADS)

Normann, Richard A.; Greger, Bradley A.; House, Paul; Romero, Samuel F.; Pelayo, Francisco; Fernandez, Eduardo

2009-06-01

Motivated by the success of cochlear implants for deaf patients, we are now facing the goal of creating a visual neuroprosthesis designed to interface with the occipital cortex as a means through which a limited but useful sense of vision could be restored in profoundly blind patients. We review the most important challenges regarding this neuroprosthetic approach and emphasize the need for basic human psychophysical research on the best way of presenting complex stimulating patterns through multiple microelectrodes. Continued research will hopefully lead to the development of and design specifications for the first generation of a cortically based visual prosthesis system.

Prediction of STN-DBS Electrode Implantation Track in Parkinson's Disease by Using Local Field Potentials

PubMed Central

Telkes, Ilknur; Jimenez-Shahed, Joohi; Viswanathan, Ashwin; Abosch, Aviva; Ince, Nuri F.

2016-01-01

Optimal electrophysiological placement of the DBS electrode may lead to better long term clinical outcomes. Inter-subject anatomical variability and limitations in stereotaxic neuroimaging increase the complexity of physiological mapping performed in the operating room. Microelectrode single unit neuronal recording remains the most common intraoperative mapping technique, but requires significant expertise and is fraught by potential technical difficulties including robust measurement of the signal. In contrast, local field potentials (LFPs), owing to their oscillatory and robust nature and being more correlated with the disease symptoms, can overcome these technical issues. Therefore, we hypothesized that multiple spectral features extracted from microelectrode-recorded LFPs could be used to automate the identification of the optimal track and the STN localization. In this regard, we recorded LFPs from microelectrodes in three tracks from 22 patients during DBS electrode implantation surgery at different depths and aimed to predict the track selected by the neurosurgeon based on the interpretation of single unit recordings. A least mean square (LMS) algorithm was used to de-correlate LFPs in each track, in order to remove common activity between channels and increase their spatial specificity. Subband power in the beta band (11–32 Hz) and high frequency range (200–450 Hz) were extracted from the de-correlated LFP data and used as features. A linear discriminant analysis (LDA) method was applied both for the localization of the dorsal border of STN and the prediction of the optimal track. By fusing the information from these low and high frequency bands, the dorsal border of STN was localized with a root mean square (RMS) error of 1.22 mm. The prediction accuracy for the optimal track was 80%. Individual beta band (11–32 Hz) and the range of high frequency oscillations (200–450 Hz) provided prediction accuracies of 72 and 68% respectively. The best prediction result obtained with monopolar LFP data was 68%. These results establish the initial evidence that LFPs can be strategically fused with computational intelligence in the operating room for STN localization and the selection of the track for chronic DBS electrode implantation. PMID:27242404

Monitoring the evolution of boron doped porous diamond electrode on flexible retinal implant by OCT and in vivo impedance spectroscopy.

PubMed

Hébert, Clément; Cottance, Myline; Degardin, Julie; Scorsone, Emmanuel; Rousseau, Lionel; Lissorgues, Gaelle; Bergonzo, Philippe; Picaud, Serge

2016-12-01

Nanocrystalline Boron doped Diamond proved to be a very attractive material for neural interfacing, especially with the retina, where reduce glia growth is observed with respect to other materials, thus facilitating neuro-stimulation over long terms. In the present study, we integrated diamond microelectrodes on a polyimide substrate and investigated their performances for the development of neural prosthesis. A full description of the microfabrication of the implants is provided and their functionalities are assessed using cyclic voltammetry and electrochemical impedance spectroscopy. A porous structure of the electrode surface was thus revealed and showed promising properties for neural recording or stimulation. Using the flexible implant, we showed that is possible to follow in vivo the evolution of the electric contact between the diamond electrodes and the retina over 4months by using electrochemical impedance spectroscopy. The position of the implant was also monitored by optical coherence tomography to corroborate the information given by the impedance measurements. The results suggest that diamond microelectrodes are very good candidates for retinal prosthesis. Copyright © 2016. Published by Elsevier B.V.

Bio-inspired hybrid microelectrodes: a hybrid solution to improve long-term performance of chronic intracortical implants.

PubMed

De Faveri, Sara; Maggiolini, Emma; Miele, Ermanno; De Angelis, Francesco; Cesca, Fabrizia; Benfenati, Fabio; Fadiga, Luciano

2014-01-01

The use of implants that allow chronic electrical stimulation and recording in the brain of human patients is currently limited by a series of events that cause the deterioration over time of both the electrode surface and the surrounding tissue. The main reason of failure is the tissue inflammatory reaction that eventually causes neuronal loss and glial encapsulation, resulting in a progressive increase of the electrode-electrolyte impedance. Here, we describe a new method to create bio-inspired electrodes to mimic the mechanical properties and biological composition of the host tissue. This combination has a great potential to increase the implant lifetime by reducing tissue reaction and improving electrical coupling. Our method implies coating the electrode with reprogrammed neural or glial cells encapsulated within a hydrogel layer. We chose fibrin as a hydrogel and primary hippocampal neurons or astrocytes from rat brain as cellular layer. We demonstrate that fibrin coating is highly biocompatible, forms uniform coatings of controllable thickness, does not alter the electrochemical properties of the microelectrode and allows good quality recordings. Moreover, it reduces the amount of host reactive astrocytes - over time - compared to a bare wire and is fully reabsorbed by the surrounding tissue within 7 days after implantation, avoiding the common problem of hydrogels swelling. Both astrocytes and neurons could be successfully grown onto the electrode surface within the fibrin hydrogel without altering the electrochemical properties of the microelectrode. This bio-hybrid device has therefore a good potential to improve the electrical integration at the neuron-electrode interface and support the long-term success of neural prostheses.

Inhibition of the cluster of differentiation 14 innate immunity pathway with IAXO-101 improves chronic microelectrode performance

NASA Astrophysics Data System (ADS)

Hermann, John K.; Ravikumar, Madhumitha; Shoffstall, Andrew J.; Ereifej, Evon S.; Kovach, Kyle M.; Chang, Jeremy; Soffer, Arielle; Wong, Chun; Srivastava, Vishnupriya; Smith, Patrick; Protasiewicz, Grace; Jiang, Jingle; Selkirk, Stephen M.; Miller, Robert H.; Sidik, Steven; Ziats, Nicholas P.; Taylor, Dawn M.; Capadona, Jeffrey R.

2018-04-01

Objective. Neuroinflammatory mechanisms are hypothesized to contribute to intracortical microelectrode failures. The cluster of differentiation 14 (CD14) molecule is an innate immunity receptor involved in the recognition of pathogens and tissue damage to promote inflammation. The goal of the study was to investigate the effect of CD14 inhibition on intracortical microelectrode recording performance and tissue integration. Approach. Mice implanted with intracortical microelectrodes in the motor cortex underwent electrophysiological characterization for 16 weeks, followed by endpoint histology. Three conditions were examined: (1) wildtype control mice, (2) knockout mice lacking CD14, and (3) wildtype control mice administered a small molecule inhibitor to CD14 called IAXO-101. Main results. The CD14 knockout mice exhibited acute but not chronic improvements in intracortical microelectrode performance without significant differences in endpoint histology. Mice receiving IAXO-101 exhibited significant improvements in recording performance over the entire 16 week duration without significant differences in endpoint histology. Significance. Full removal of CD14 is beneficial at acute time ranges, but limited CD14 signaling is beneficial at chronic time ranges. Innate immunity receptor inhibition strategies have the potential to improve long-term intracortical microelectrode performance.

An implantable integrated low-power amplifier-microelectrode array for Brain-Machine Interfaces.

PubMed

Patrick, Erin; Sankar, Viswanath; Rowe, William; Sanchez, Justin C; Nishida, Toshikazu

2010-01-01

One of the important challenges in designing Brain-Machine Interfaces (BMI) is to build implantable systems that have the ability to reliably process the activity of large ensembles of cortical neurons. In this paper, we report the design, fabrication, and testing of a polyimide-based microelectrode array integrated with a low-power amplifier as part of the Florida Wireless Integrated Recording Electrode (FWIRE) project at the University of Florida developing a fully implantable neural recording system for BMI applications. The electrode array was fabricated using planar micromachining MEMS processes and hybrid packaged with the amplifier die using a flip-chip bonding technique. The system was tested both on bench and in-vivo. Acute and chronic neural recordings were obtained from a rodent for a period of 42 days. The electrode-amplifier performance was analyzed over the chronic recording period with the observation of a noise floor of 4.5 microVrms, and an average signal-to-noise ratio of 3.8.

Alkaline biodegradable implants for osteoporotic bone defects--importance of microenvironment pH.

PubMed

Liu, W; Wang, T; Yang, C; Darvell, B W; Wu, J; Lin, K; Chang, J; Pan, H; Lu, W W

2016-01-01

Change of microenvironment pH by biodegradable implants may ameliorate unbalanced osteoporotic bone remodeling. The present work demonstrated that a weak alkaline condition stimulated osteoblasts differentiation while suppressed osteoclast generation. In vivo, implants with an alkaline microenvironment pH (monitored by a pH microelectrode) exhibited a promising healing effect for the repair of osteoporotic bone defects. Under osteoporotic conditions, the response of the bone microenvironment to an endosseous implant is significantly impaired, and this substantially increases the risk of fracture, non-union and aseptic implant loosening. Acid-base equilibrium is an important factor influencing bone cell behaviour. The present purpose was to study the effect of a series of alkaline biodegradable implant materials on regeneration of osteoporotic bone defect, monitoring the microenvironment pH (μe-pH) over time. The proliferation and differentiation potential of osteoporotic rat bone marrow stromal cells and RAW 264.7 cells were examined under various pH conditions. Ovariectomized rat bone defects were filled with specific biodegradable materials, and μe-pH was measured by pH microelectrode. New osteoid and tartrate-resistant acid phosphatase-positive osteoclast-like cells were examined by Goldner's trichrome and TRAP staining, respectively. The intermediate layer between implants and new bone were studied using energy-dispersive X-ray spectroscopy (EDX) linear scanning. In vitro, weak alkaline conditions stimulated osteoporotic rat bone marrow stromal cells (oBMSC) differentiation, while inhibiting the formation of osteoclasts. In vivo, μe-pH differs from that of the homogeneous peripheral blood and exhibits variations over time particular to each material. Higher initial μe-pH was associated with more new bone formation, late response of TRAP-positive osteoclast-like cells and the development of an intermediate 'apatitic' layer in vivo. EDX suggested that residual material may influence μe-pH even 9 weeks post-surgery. The pH microelectrode is suitable for in vivo μe-pH detection. Alkaline biodegradable materials generate an in vivo microenvironmental pH which is higher than the normal physiological value and show promising healing effects in the context of osteoporotic bone defects.

Deep brain stimulation macroelectrodes compared to multiple microelectrodes in rat hippocampus

PubMed Central

Arcot Desai, Sharanya; Gutekunst, Claire-Anne; Potter, Steve M.; Gross, Robert E.

2014-01-01

Microelectrode arrays (wire diameter <50 μm) were compared to traditional macroelectrodes for deep brain stimulation (DBS). Understanding the neuronal activation volume may help solve some of the mysteries associated with DBS, e.g., its mechanisms of action. We used c-fos immunohistochemistry to investigate neuronal activation in the rat hippocampus caused by multi-micro- and macroelectrode stimulation. At ± 1V stimulation at 25 Hz, microelectrodes (33 μm diameter) had a radius of activation of 100 μm, which is 50% of that seen with 150 μm diameter macroelectrode stimulation. Macroelectrodes activated about 5.8 times more neurons than a single microelectrode, but displaced ~20 times more neural tissue. The sphere of influence of stimulating electrodes can be significantly increased by reducing their impedance. By ultrasonic electroplating (sonicoplating) the microelectrodes with platinum to increase their surface area and reduce their impedance by an order of magnitude, the radius of activation increased by 50 μm and more than twice the number of neurons were activated within this increased radius compared to unplated microelectrodes. We suggest that a new approach to DBS, one that uses multiple high-surface area microelectrodes, may be more therapeutically effective due to increased neuronal activation. PMID:24971060

Bio-inspired hybrid microelectrodes: a hybrid solution to improve long-term performance of chronic intracortical implants

PubMed Central

De Faveri, Sara; Maggiolini, Emma; Miele, Ermanno; De Angelis, Francesco; Cesca, Fabrizia; Benfenati, Fabio; Fadiga, Luciano

2014-01-01

The use of implants that allow chronic electrical stimulation and recording in the brain of human patients is currently limited by a series of events that cause the deterioration over time of both the electrode surface and the surrounding tissue. The main reason of failure is the tissue inflammatory reaction that eventually causes neuronal loss and glial encapsulation, resulting in a progressive increase of the electrode-electrolyte impedance. Here, we describe a new method to create bio-inspired electrodes to mimic the mechanical properties and biological composition of the host tissue. This combination has a great potential to increase the implant lifetime by reducing tissue reaction and improving electrical coupling. Our method implies coating the electrode with reprogrammed neural or glial cells encapsulated within a hydrogel layer. We chose fibrin as a hydrogel and primary hippocampal neurons or astrocytes from rat brain as cellular layer. We demonstrate that fibrin coating is highly biocompatible, forms uniform coatings of controllable thickness, does not alter the electrochemical properties of the microelectrode and allows good quality recordings. Moreover, it reduces the amount of host reactive astrocytes – over time – compared to a bare wire and is fully reabsorbed by the surrounding tissue within 7 days after implantation, avoiding the common problem of hydrogels swelling. Both astrocytes and neurons could be successfully grown onto the electrode surface within the fibrin hydrogel without altering the electrochemical properties of the microelectrode. This bio-hybrid device has therefore a good potential to improve the electrical integration at the neuron-electrode interface and support the long-term success of neural prostheses. PMID:24782757

Ultrasoft microwire neural electrodes improve chronic tissue integration.

PubMed

Du, Zhanhong Jeff; Kolarcik, Christi L; Kozai, Takashi D Y; Luebben, Silvia D; Sapp, Shawn A; Zheng, Xin Sally; Nabity, James A; Cui, X Tracy

2017-04-15

Chronically implanted neural multi-electrode arrays (MEA) are an essential technology for recording electrical signals from neurons and/or modulating neural activity through stimulation. However, current MEAs, regardless of the type, elicit an inflammatory response that ultimately leads to device failure. Traditionally, rigid materials like tungsten and silicon have been employed to interface with the relatively soft neural tissue. The large stiffness mismatch is thought to exacerbate the inflammatory response. In order to minimize the disparity between the device and the brain, we fabricated novel ultrasoft electrodes consisting of elastomers and conducting polymers with mechanical properties much more similar to those of brain tissue than previous neural implants. In this study, these ultrasoft microelectrodes were inserted and released using a stainless steel shuttle with polyethyleneglycol (PEG) glue. The implanted microwires showed functionality in acute neural stimulation. When implanted for 1 or 8weeks, the novel soft implants demonstrated significantly reduced inflammatory tissue response at week 8 compared to tungsten wires of similar dimension and surface chemistry. Furthermore, a higher degree of cell body distortion was found next to the tungsten implants compared to the polymer implants. Our results support the use of these novel ultrasoft electrodes for long term neural implants. One critical challenge to the translation of neural recording/stimulation electrode technology to clinically viable devices for brain computer interface (BCI) or deep brain stimulation (DBS) applications is the chronic degradation of device performance due to the inflammatory tissue reaction. While many hypothesize that soft and flexible devices elicit reduced inflammatory tissue responses, there has yet to be a rigorous comparison between soft and stiff implants. We have developed an ultra-soft microelectrode with Young's modulus lower than 1MPa, closely mimicking the brain tissue modulus. Here, we present a rigorous histological comparison of this novel ultrasoft electrode and conventional stiff electrode with the same size, shape and surface chemistry, implanted in rat brains for 1-week and 8-weeks. Significant improvement was observed for ultrasoft electrodes, including inflammatory tissue reaction, electrode-tissue integration as well as mechanical disturbance to nearby neurons. A full spectrum of new techniques were developed in this study, from insertion shuttle to in situ sectioning of the microelectrode to automated cell shape analysis, all of which should contribute new methods to the field. Finally, we showed the electrical functionality of the ultrasoft electrode, demonstrating the potential of flexible neural implant devices for future research and clinical use. Copyright © 2017. Published by Elsevier Ltd.

[Microelectrode study of the cellular reactions of the taste bud in the frog Rana temporaria].

PubMed

Lotarev, A N; Samoĭlov, V O

1986-01-01

Microelectrophysiological studies reveal two types of cells in the taste bud of frog which differ by the level of their membrane potential. During vertical implantation of microelectrode through the apical part of the taste bud, the potential difference in the upper layer amounts to 15 mV. Further implantation of the electrode results in a stepwise decrease of the potential difference up to 27 mV. Cells of the deeper layer are located 12-24 micron lower from the apical surface. Stimulation of cells by solutions of chemical substances is accompanied by cell depolarization, its amplitude being proportional to stimulus concentration. The steepness of depolarization depends on the modality of the stimulus, being maximum for salts. The data obtained suggest that cells of the second layer, with a higher resting membrane potential level, are taste ones.

Theoretical analysis of intracortical microelectrode recordings

NASA Astrophysics Data System (ADS)

Lempka, Scott F.; Johnson, Matthew D.; Moffitt, Michael A.; Otto, Kevin J.; Kipke, Daryl R.; McIntyre, Cameron C.

2011-08-01

Advanced fabrication techniques have now made it possible to produce microelectrode arrays for recording the electrical activity of a large number of neurons in the intact brain for both clinical and basic science applications. However, the long-term recording performance desired for these applications is hindered by a number of factors that lead to device failure or a poor signal-to-noise ratio (SNR). The goal of this study was to identify factors that can affect recording quality using theoretical analysis of intracortical microelectrode recordings of single-unit activity. Extracellular microelectrode recordings were simulated with a detailed multi-compartment cable model of a pyramidal neuron coupled to a finite-element volume conductor head model containing an implanted recording microelectrode. Recording noise sources were also incorporated into the overall modeling infrastructure. The analyses of this study would be very difficult to perform experimentally; however, our model-based approach enabled a systematic investigation of the effects of a large number of variables on recording quality. Our results demonstrate that recording amplitude and noise are relatively independent of microelectrode size, but instead are primarily affected by the selected recording bandwidth, impedance of the electrode-tissue interface and the density and firing rates of neurons surrounding the recording electrode. This study provides the theoretical groundwork that allows for the design of the microelectrode and recording electronics such that the SNR is maximized. Such advances could help enable the long-term functionality required for chronic neural recording applications.

Theoretical analysis of intracortical microelectrode recordings

PubMed Central

Lempka, Scott F; Johnson, Matthew D; Moffitt, Michael A; Otto, Kevin J; Kipke, Daryl R; McIntyre, Cameron C

2011-01-01

Advanced fabrication techniques have now made it possible to produce microelectrode arrays for recording the electrical activity of a large number of neurons in the intact brain for both clinical and basic science applications. However, the long-term recording performance desired for these applications is hindered by a number of factors that lead to device failure or a poor signal-to-noise ratio (SNR). The goal of this study was to identify factors that can affect recording quality using theoretical analysis of intracortical microelectrode recordings of single-unit activity. Extracellular microelectrode recordings were simulated with a detailed multi-compartment cable model of a pyramidal neuron coupled to a finite element volume conductor head model containing an implanted recording microelectrode. Recording noise sources were also incorporated into the overall modeling infrastructure. The analyses of this study would be very difficult to perform experimentally; however, our model-based approach enabled a systematic investigation of the effects of a large number of variables on recording quality. Our results demonstrate that recording amplitude and noise are relatively independent of microelectrode size, but instead are primarily affected by the selected recording bandwidth, impedance of the electrode-tissue interface, and the density and firing rates of neurons surrounding the recording electrode. This study provides the theoretical groundwork that allows for the design of the microelectrode and recording electronics such that the SNR is maximized. Such advances could help enable the long-term functionality required for chronic neural recording applications. PMID:21775783

Foreign Body Response to Intracortical Microelectrodes Is Not Altered with Dip-Coating of Polyethylene Glycol (PEG)

PubMed Central

Lee, Heui C.; Gaire, Janak; Currlin, Seth W.; McDermott, Matthew D.; Park, Kinam; Otto, Kevin J.

2017-01-01

Poly(ethylene glycol) (PEG) is a frequently used polymer for neural implants due to its biocompatible property. As a follow-up to our recent study that used PEG for stiffening flexible neural probes, we have evaluated the biological implications of using devices dip-coated with PEG for chronic neural implants. Mice (wild-type and CX3CR1-GFP) received bilateral implants within the sensorimotor cortex, one hemisphere with a PEG-coated probe and the other with a non-coated probe for 4 weeks. Quantitative analyses were performed using biomarkers for activated microglia/macrophages, astrocytes, blood-brain barrier leakage, and neuronal nuclei to determine the degree of foreign body response (FBR) resulting from the implanted microelectrodes. Despite its well-known acute anti-biofouling property, we observed that PEG-coated devices caused no significantly different FBR compared to non-coated controls at 4 weeks. A repetition using CX3CR1-GFP mice cohort showed similar results. Our histological findings suggest that there is no significant impact of acute delivery of PEG on the FBR in the long-term, and that temporary increase in the device footprint due to the coating of PEG also does not have a significant impact. Large variability seen within the same treatment group also implies that avoiding large superficial vasculature during implantation is not sufficient to minimize inter-animal variability. PMID:28959183

Microelectrode Recordings Validate the Clinical Visualization of Subthalamic-Nucleus Based on 7T Magnetic Resonance Imaging and Machine Learning for Deep Brain Stimulation Surgery.

PubMed

Shamir, Reuben R; Duchin, Yuval; Kim, Jinyoung; Patriat, Remi; Marmor, Odeya; Bergman, Hagai; Vitek, Jerrold L; Sapiro, Guillermo; Bick, Atira; Eliahou, Ruth; Eitan, Renana; Israel, Zvi; Harel, Noam

2018-05-24

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a proven and effective therapy for the management of the motor symptoms of Parkinson's disease (PD). While accurate positioning of the stimulating electrode is critical for success of this therapy, precise identification of the STN based on imaging can be challenging. We developed a method to accurately visualize the STN on a standard clinical magnetic resonance imaging (MRI). The method incorporates a database of 7-Tesla (T) MRIs of PD patients together with machine-learning methods (hereafter 7 T-ML). To validate the clinical application accuracy of the 7 T-ML method by comparing it with identification of the STN based on intraoperative microelectrode recordings. Sixteen PD patients who underwent microelectrode-recordings guided STN DBS were included in this study (30 implanted leads and electrode trajectories). The length of the STN along the electrode trajectory and the position of its contacts to dorsal, inside, or ventral to the STN were compared using microelectrode-recordings and the 7 T-ML method computed based on the patient's clinical 3T MRI. All 30 electrode trajectories that intersected the STN based on microelectrode-recordings, also intersected it when visualized with the 7 T-ML method. STN trajectory average length was 6.2 ± 0.7 mm based on microelectrode recordings and 5.8 ± 0.9 mm for the 7 T-ML method. We observed a 93% agreement regarding contact location between the microelectrode-recordings and the 7 T-ML method. The 7 T-ML method is highly consistent with microelectrode-recordings data. This method provides a reliable and accurate patient-specific prediction for targeting the STN.

Biocompatible implants and methods of making and attaching the same

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rowley, Adrian P; Laude, Lucien D; Humayun, Mark S

2014-10-07

The invention provides a biocompatible silicone implant that can be securely affixed to living tissue through interaction with integral membrane proteins (integrins). A silicone article containing a laser-activated surface is utilized to make the implant. One example is an implantable prosthesis to treat blindness caused by outer retinal degenerative diseases. The device bypasses damaged photoreceptors and electrically stimulates the undamaged neurons of the retina. Electrical stimulation is achieved using a silicone microelectrode array (MEA). A safe, protein adhesive is used in attaching the MEA to the retinal surface and assist in alleviating focal pressure effects. Methods of making and attachingmore » such implants are also provided.« less

Optical coherence microscopy of mouse cortical vasculature surrounding implanted electrodes

NASA Astrophysics Data System (ADS)

Hammer, Daniel X.; Lozzi, Andrea; Abliz, Erkinay; Greenbaum, Noah; Turner, Kevin P.; Pfefer, T. Joshua; Agrawal, Anant; Krauthamer, Victor; Welle, Cristin G.

2014-03-01

Optical coherence microscopy (OCM) provides real-time, in-vivo, three-dimensional, isotropic micron-resolution structural and functional characterization of tissue, cells, and other biological targets. Optical coherence angiography (OCA) also provides visualization and quantification of vascular flow via speckle-based or phase-resolved techniques. Performance assessment of neuroprosthetic systems, which allow direct thought control of limb prostheses, may be aided by OCA. In particular, there is a need to examine the underlying mechanisms of chronic functional degradation of implanted electrodes. Angiogenesis, capillary network remodeling, and changes in flow velocity are potential indicators of tissue changes that may be associated with waning electrode performance. The overall goal of this investigation is to quantify longitudinal changes in vascular morphology and capillary flow around neural electrodes chronically implanted in mice. We built a 1315-nm OCM system to image vessels in neocortical tissue in a cohort of mice. An optical window was implanted on the skull over the primary motor cortex above a penetrating shank-style microelectrode array. The mice were imaged bi-weekly to generate vascular maps of the region surrounding the implanted microelectrode array. Acute effects of window and electrode implantation included vessel dilation and profusion of vessels in the superficial layer of the cortex (0-200 μm). In deeper layers surrounding the electrode, no qualitative differences were seen in this early phase. These measurements establish a baseline vascular tissue response from the cortical window preparation and lay the ground work for future longitudinal studies to test the hypothesis that vascular changes will be associated with chronic electrode degradation.

Brain machine interfaces combining microelectrode arrays with nanostructured optical biochemical sensors

NASA Astrophysics Data System (ADS)

Hajj-Hassan, Mohamad; Gonzalez, Timothy; Ghafer-Zadeh, Ebrahim; Chodavarapu, Vamsy; Musallam, Sam; Andrews, Mark

2009-02-01

Neural microelectrodes are an important component of neural prosthetic systems which assist paralyzed patients by allowing them to operate computers or robots using their neural activity. These microelectrodes are also used in clinical settings to localize the locus of seizure initiation in epilepsy or to stimulate sub-cortical structures in patients with Parkinson's disease. In neural prosthetic systems, implanted microelectrodes record the electrical potential generated by specific thoughts and relay the signals to algorithms trained to interpret these thoughts. In this paper, we describe novel elongated multi-site neural electrodes that can record electrical signals and specific neural biomarkers and that can reach depths greater than 8mm in the sulcus of non-human primates (monkeys). We hypothesize that additional signals recorded by the multimodal probes will increase the information yield when compared to standard probes that record just electropotentials. We describe integration of optical biochemical sensors with neural microelectrodes. The sensors are made using sol-gel derived xerogel thin films that encapsulate specific biomarker responsive luminophores in their nanostructured pores. The desired neural biomarkers are O2, pH, K+, and Na+ ions. As a prototype, we demonstrate direct-write patterning to create oxygen-responsive xerogel waveguide structures on the neural microelectrodes. The recording of neural biomarkers along with electrical activity could help the development of intelligent and more userfriendly neural prosthesis/brain machine interfaces as well as aid in providing answers to complex brain diseases and disorders.

Fabrication and surface-modification of implantable microprobes for neuroscience studies

NASA Astrophysics Data System (ADS)

Cao, H.; Nguyen, C. M.; Chiao, J. C.

2012-06-01

In this work implantable micro-probes for central nervous system (CNS) studies were developed on silicon and polyimide substrates. The probes which contained micro-electrode arrays with different surface modifications were designed for implantation in the CNS. The electrode surfaces were modified with nano-scale structures that could greatly increase the active surface area in order to enhance the electrochemical current outputs while maintaining micro-scale dimensions of the electrodes and probes. The electrodes were made of gold or platinum, and designed with different sizes. The silicon probes were modified by silicon nanowires fabricated with the vapor-liquid-solid mechanism at high temperatures. With polyimide substrates, the nanostructure modification was carried out by applying concentrated gold or silver colloid solutions onto the micro-electrodes at room temperature. The surfaces of electrodes before and after modification were observed by scanning electron microscopy. The silicon nanowire-modified surface was characterized by cyclic voltammetry. Experiments were carried out to investigate the improvement in sensing performance. The modified electrodes were tested with H2O2, electrochemical L-glutamate and dopamine. Comparisons between electrodes with and without nanostructure modification were conducted showing that the modifications have enhanced the signal outputs of the electrochemical neurotransmitter sensors.

3D-nanostructured boron-doped diamond for microelectrode array neural interfacing.

PubMed

Piret, Gaëlle; Hébert, Clément; Mazellier, Jean-Paul; Rousseau, Lionel; Scorsone, Emmanuel; Cottance, Myline; Lissorgues, Gaelle; Heuschkel, Marc O; Picaud, Serge; Bergonzo, Philippe; Yvert, Blaise

2015-06-01

The electrode material is a key element in the design of long-term neural implants and neuroprostheses. To date, the ideal electrode material offering high longevity, biocompatibility, low-noise recording and high stimulation capabilities remains to be found. We show that 3D-nanostructured boron doped diamond (BDD), an innovative material consisting in a chemically stable material with a high aspect ratio structure obtained by encapsulation of a carbon nanotube template within two BDD nanolayers, allows neural cell attachment, survival and neurite extension. Further, we developed arrays of 20-μm-diameter 3D-nanostructured BDD microelectrodes for neural interfacing. These microelectrodes exhibited low impedances and low intrinsic recording noise levels. In particular, they allowed the detection of low amplitude (10-20 μV) local-field potentials, single units and multiunit bursts neural activity in both acute whole embryonic hindbrain-spinal cord preparations and long-term hippocampal cell cultures. Also, cyclic voltammetry measurements showed a wide potential window of about 3 V and a charge storage capacity of 10 mC.cm(-2), showing high potentiality of this material for neural stimulation. These results demonstrate the attractiveness of 3D-nanostructured BDD as a novel material for neural interfacing, with potential applications for the design of biocompatible neural implants for the exploration and rehabilitation of the nervous system. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Extracellular pH monitoring for use in closed-loop vagus nerve stimulation

NASA Astrophysics Data System (ADS)

Cork, Simon C.; Eftekhar, Amir; Mirza, Khalid B.; Zuliani, Claudio; Nikolic, Konstantin; Gardiner, James V.; Bloom, Stephen R.; Toumazou, Christofer

2018-02-01

Objective. Vagal nerve stimulation (VNS) has shown potential benefits for obesity treatment; however, current devices lack physiological feedback, which limit their efficacy. Changes in extracellular pH (pHe) have shown to be correlated with neural activity, but have traditionally been measured with glass microelectrodes, which limit their in vivo applicability. Approach. Iridium oxide has previously been shown to be sensitive to fluctuations in pH and is biocompatible. Iridium oxide microelectrodes were inserted into the subdiaphragmatic vagus nerve of anaesthetised rats. Introduction of the gut hormone cholecystokinin (CCK) or distension of the stomach was used to elicit vagal nerve activity. Main results. Iridium oxide microelectrodes have sufficient pH sensitivity to readily detect changes in pHe associated with both CCK and gastric distension. Furthermore, a custom-made Matlab script was able to use these changes in pHe to automatically trigger an implanted VNS device. Significance. This is the first study to show pHe changes in peripheral nerves in vivo. In addition, the demonstration that iridium oxide microelectrodes are sufficiently pH sensitive as to measure changes in pHe associated with physiological stimuli means they have the potential to be integrated into closed-loop neurostimulating devices.

3D hybrid electrode structure as implantable interface for a vestibular neural prosthesis in humans.

PubMed

Hoffmann, Klaus-P; Poppendieck, Wigand; Tätzner, Simon; DiGiovanna, Jack; Kos, Maria Izabel; Guinand, Nils; Guyot, Jean-P; Micera, Silvestro

2011-01-01

Implantable interfaces are essential components of vestibular neural prostheses. They interface the biological system with electrical stimulation that is used to restore transfer of vestibular information. Regarding the anatomical situation special 3D structures are required. In this paper, the design and the manufacturing process of a novel 3D hybrid microelectrode structure as interface to the human vestibular system are described. Photolithography techniques, assembling technology and rapid prototyping are used for manufacturing.

Microelectrode Arrays: A Physiologically-based Neurotoxicity Testing Platform for the 21st Century

EPA Science Inventory

Microelectrode Arrays (MEAs) have been in use over the past decade and a half to study multiple aspects ofelectrically excitable cells. Inparticular, MEAs have been applied to explore the pharmacological and toxicological effects ofnumerous compounds on spontaneous activity ofneu...

Methods, caveats and the future of large-scale microelectrode recordings in the non-human primate

PubMed Central

Dotson, Nicholas M.; Goodell, Baldwin; Salazar, Rodrigo F.; Hoffman, Steven J.; Gray, Charles M.

2015-01-01

Cognitive processes play out on massive brain-wide networks, which produce widely distributed patterns of activity. Capturing these activity patterns requires tools that are able to simultaneously measure activity from many distributed sites with high spatiotemporal resolution. Unfortunately, current techniques with adequate coverage do not provide the requisite spatiotemporal resolution. Large-scale microelectrode recording devices, with dozens to hundreds of microelectrodes capable of simultaneously recording from nearly as many cortical and subcortical areas, provide a potential way to minimize these tradeoffs. However, placing hundreds of microelectrodes into a behaving animal is a highly risky and technically challenging endeavor that has only been pursued by a few groups. Recording activity from multiple electrodes simultaneously also introduces several statistical and conceptual dilemmas, such as the multiple comparisons problem and the uncontrolled stimulus response problem. In this perspective article, we discuss some of the techniques that we, and others, have developed for collecting and analyzing large-scale data sets, and address the future of this emerging field. PMID:26578906

Influence of cochleostomy and cochlear implant insertion on drug gradients following intratympanic application in guinea pigs

PubMed Central

King, EB; Hartsock, JJ; O'Leary, SJ; Salt, AN

2013-01-01

Locally-applied drugs can protect residual hearing following cochlear implantation. The influence of cochlear implantation on drug levels in scala tympani (ST) after round window application was investigated in guinea pigs using the marker trimethylphenlyammonium (TMPA) measured in real-time with TMPA-selective microelectrodes. TMPA concentration in the upper basal turn of ST rapidly increased during implantation and then declined due to cerebrospinal fluid entering ST at the cochlear aqueduct and exiting at the cochleostomy. The TMPA increase was found to be caused by the cochleostomy drilling, if the burr tip partially entered ST. TMPA distribution in the second turn was less affected by implantation procedures. These findings show that basal turn drug levels may be changed during implantation and the changes may need to be considered in the interpretation of therapeutic effects of drugs in conjunction with implantation. PMID:24008355

Lower layers in the motor cortex are more effective targets for penetrating microelectrodes in cortical prostheses

NASA Astrophysics Data System (ADS)

Parikh, Hirak; Marzullo, Timothy C.; Kipke, Daryl R.

2009-04-01

Improving cortical prostheses requires the development of recording neural interfaces that are efficient in terms of providing maximal control information with minimal interface complexity. While the typical approaches have targeted neurons in the motor cortex with multiple penetrating shanks, an alternative approach is to determine an efficient distribution of electrode sites within the layers of the cortex with fewer penetrating shanks. The objective of this study was to compare unit activity in the upper and lower layers of the cortex with respect to movement and direction in order to inform the design of penetrating microelectrodes. Four rats were implanted bilaterally with multi-site single-shank silicon microelectrode arrays in the neck/shoulder region of the motor cortex. We simultaneously recorded unit activity across all layers of the motor cortex while the animal was engaged in a movement direction task. Localization of the electrode array within the different layers of the cortex was determined by histology. We denoted units from layers 2 and 3 and units as upper layer units, and units from layers 5 and 6 as lower layer units. Analysis of unit spiking activity demonstrated that both the upper and lower layers encode movement and direction information. Unit responses in either cortical layer of the cortex were not preferentially associated with contralateral or ipsilateral movement. Aggregate analysis (633 neurons) and best session analysis (75 neurons) indicated that units in the lower layers (layers 5, 6) are more likely to encode direction information when compared to units in the upper layers (layers 2, 3) (p< 0.05). These results suggest that electrode sites clustered in the lower layers provide access to more salient control information for cortical neuroprostheses.

Chronic monitoring of lower urinary tract activity via a sacral dorsal root ganglia interface

NASA Astrophysics Data System (ADS)

Khurram, Abeer; Ross, Shani E.; Sperry, Zachariah J.; Ouyang, Aileen; Stephan, Christopher; Jiman, Ahmad A.; Bruns, Tim M.

2017-06-01

Objective. Our goal is to develop an interface that integrates chronic monitoring of lower urinary tract (LUT) activity with stimulation of peripheral pathways. Approach. Penetrating microelectrodes were implanted in sacral dorsal root ganglia (DRG) of adult male felines. Peripheral electrodes were placed on or in the pudendal nerve, bladder neck and near the external urethral sphincter. Supra-pubic bladder catheters were implanted for saline infusion and pressure monitoring. Electrode and catheter leads were enclosed in an external housing on the back. Neural signals from microelectrodes and bladder pressure of sedated or awake-behaving felines were recorded under various test conditions in weekly sessions. Electrodes were also stimulated to drive activity. Main results. LUT single- and multi-unit activity was recorded for 4-11 weeks in four felines. As many as 18 unique bladder pressure single-units were identified in each experiment. Some channels consistently recorded bladder afferent activity for up to 41 d, and we tracked individual single-units for up to 23 d continuously. Distension-evoked and stimulation-driven (DRG and pudendal) bladder emptying was observed, during which LUT sensory activity was recorded. Significance. This chronic implant animal model allows for behavioral studies of LUT neurophysiology and will allow for continued development of a closed-loop neuroprosthesis for bladder control.

Mathematical modeling of chemotaxis and glial scarring around implanted electrodes

NASA Astrophysics Data System (ADS)

Silchenko, Alexander N.; Tass, Peter A.

2015-02-01

It is well known that the implantation of electrodes for deep brain stimulation or microelectrode probes for the recording of neuronal activity is always accompanied by the response of the brain’s immune system leading to the formation of a glial scar around the implantation sites. The implantation of electrodes causes massive release of adenosine-5‧-triphosphate (ATP) and different cytokines into the extracellular space and activates the microglia. The released ATP and the products of its hydrolysis, such as ADP and adenosine, become the main elements mediating chemotactic sensitivity and motility of microglial cells via subsequent activation of P2Y2,12 as well as A3A/A2A adenosine receptors. The size and density of an insulating sheath around the electrode, formed by microglial cells, are important criteria for the optimization of the signal-to-noise ratio during microelectrode recordings or parameters of electrical current delivered to the brain tissue. Here, we study a purinergic signaling pathway underlying the chemotactic motion of microglia towards implanted electrodes as well as the possible impact of an anti-inflammatory coating consisting of the interleukin-1 receptor antagonist. We present a model describing the formation of a stable aggregate around the electrode due to the joint chemo-attractive action of ATP and ADP and the mixed influence of extracellular adenosine. The bioactive coating is modeled as a source of chemo-repellent located near the electrode surface. The obtained analytical and numerical results allowed us to reveal the dependences of size and spatial location of the insulating sheath on the amount of released ATP and estimate the impact of immune suppressive coating on the scarring process.

An improved method for constructing and selectively silanizing double-barreled, neutral liquid-carrier, ion-selective microelectrodes

PubMed Central

Deveau, Jason S.T.; Grodzinski, Bernard

2005-01-01

We describe an improved, efficient and reliable method for the vapour-phase silanization of multi-barreled, ion-selective microelectrodes of which the silanized barrel(s) are to be filled with neutral liquid ion-exchanger (LIX). The technique employs a metal manifold to exclusively and simultaneously deliver dimethyldichlorosilane to only the ion-selective barrels of several multi-barreled microelectrodes. Compared to previously published methods the technique requires fewer procedural steps, less handling of individual microelectrodes, improved reproducibility of silanization of the selected microelectrode barrels and employs standard borosilicate tubing rather than the less-conventional theta-type glass. The electrodes remain stable for up to 3 weeks after the silanization procedure. The efficacy of a double-barreled electrode containing a proton ionophore in the ion-selective barrel is demonstrated in situ in the leaf apoplasm of pea (Pisum) and sunflower (Helianthus). Individual leaves were penetrated to depth of ~150 μm through the abaxial surface. Microelectrode readings remained stable after multiple impalements without the need for a stabilizing PVC matrix. PMID:16136222

Highly Sensitive and Long Term Stable Electrochemical Microelectrodes for Implantable Glucose Monitoring Devices

NASA Astrophysics Data System (ADS)

Qiang, Liangliang

A miniature wireless implantable electrochemical glucose system for continuous glucose monitoring with good selectivity, sensitivity, linearity and long term stability was developed. First, highly sensitive, long-term stable and reusable planar H2O2 microelectrodes have been fabricated by microlithography. These electrodes composed of a 300 nm Pt black layer situated on a 5 um thick Au layer, provide effective protection to the underlying chromium adhesion layer. Using repeated cyclic voltammetric sweeps in flowing buffer solution, highly sensitive Pt black working electrodes were realized with five-decade linear dynamic range and low detection limit (10 nM) for H2O2 at low oxidation potentials. Second, a highly sensitive, low cost and flexible microwire biosensor was described using 25-mum thick gold wire as working electrode together with 125-mum thick Pt/Ir and Ag wires as counter and reference electrode, embedded within a PDMS-filled polyethylene tube. Surface area and activity of sensor was enhanced by converting gold electrode to nanoporous configuration followed by electrodeposition of platinum black. Glucose oxidase based biosensors by electrodeposition of poly(o-phenylenediamine) and glucose oxidase on the working electrode, displayed a higher glucose sensitivity (1.2 mA mM-1 cm-2) than highest literature reported. In addition it exhibits wide detection range (up to 20 mM) and selectivity (>95%). Third, novel miniaturized and flexible microelectrode arrays with 8 of 25 mum electrodes displayed the much needed 3D diffusion profiles similar to a single 25 mum microelectrode, but with one order increase in current levels. These microelectrode arrays displayed a H2O2 sensitivity of 13 mA mM-1 cm-2, a wide dynamic range of 100 nM to 10 mM, limit of detection of 10 nM. These microwire based edge plane microsensors incorporated flexibility, miniaturization and low operation potential are an promising approach for continuous in vivo metabolic monitoring. Fourth, homemade miniature wireless potentisotat was fabricated based on low power consumption integrated circuits and surface mount parts. The miniature wireless potentisotat with up to two week life-time for continuous glucose sensing has a size less than 9x22x10 mm and weight ˜3.4 grams. Primary in vivo experiment showed homemade system has the exactly same respond and trend as commercial glucose meter.

Preventing neuronal damage and inflammation in vivo during cortical microelectrode implantation through the use of Poloxamer P-188

NASA Astrophysics Data System (ADS)

Misra, A.; Kondaveeti, P.; Nissanov, J.; Barbee, K.; Shewokis, P.; Rioux, L.; Moxon, K. A.

2013-02-01

Objective. The aim of this study was to test the efficacy of Poloxamer P188 to reduce cell death and immune response associated with mechanical trauma to cells during implantation of a chronic recording electrode. Approach. Ceramic multi-site recording electrodes were implanted bilaterally into 15 adult male Long-Evans rats. One of each pair was randomly assigned to receive a coating of Poloxamer while the other was treated with saline. The extent of neuron loss, and glial cell recruitment were characterized at 2, 4 and 6 weeks post-implantation by stereologic analysis. Main results. At 2 and 4 weeks post-implantation, Poloxamer-coated implants showed significantly fewer glial cells and more neurons in the peri-electrode space than controls; however, this significance was lost by 6 weeks. Significance. These findings are the first to suggest that Poloxamer has neuroprotective effects in vivo; however, at a fixed loading dose, these effects are limited to approximately 1 month post-implantation.

Design and fabrication of a polyimide-based microelectrode array: application in neural recording and repeatable electrolytic lesion in rat brain.

PubMed

Chen, You-Yin; Lai, Hsin-Yi; Lin, Sheng-Huang; Cho, Chien-Wen; Chao, Wen-Hung; Liao, Chia-Hsin; Tsang, Siny; Chen, Yi-Fan; Lin, Si-Yue

2009-08-30

The design and testing of a new microelectrode array, the NCTU (National Chiao Tung University) probe, was presented. Evaluation results showed it has good biocompatibility, high signal-to-noise ratio (SNR: the root mean square of background noise to the average peak-to-peak amplitude of spikes) during chronic neural recordings, and high reusability for electrolytic lesions. The probe was a flexible, polyimide-based microelectrode array with a long shaft (14.9 mm in length) and 16 electrodes (5 microm-thick and 16 microm in radius); its performance in chronic in vivo recordings was examined in rodents. To improve the precision of implantation, a metallic, impact-resistant layer was sandwiched between the polyimide layers to strengthen the probe. The three-dimensional (3D) structure of electrodes fabricated by electroplating produced rough textures that increased the effective surface area. The in vitro impedance of electrodes on the NCTU probe was 2.4+/-0.52 MOmega at 1 kHz. In addition, post-surgical neural recordings of implanted NCTU probes were conducted for up to 40 days in awake, normally behaving rats. The electrodes on the NCTU probe functioned well and had a high SNR (range: 4-5) with reliable in vivo impedance (<0.7 MOmega). The electrodes were also robust enough to functionally record events, even after the anodal current (30 microA, 10s) was repeatedly applied for 60 times. With good biocompatibility, high and stable SNR for chronic recording, and high tolerance for electrolytic lesion, the NCTU probe would serve as a useful device in future neuroscience research.

Active Microelectronic Neurosensor Arrays for Implantable Brain Communication Interfaces

PubMed Central

Song, Y.-K.; Borton, D. A.; Park, S.; Patterson, W. R.; Bull, C. W.; Laiwalla, F.; Mislow, J.; Simeral, J. D.; Donoghue, J. P.; Nurmikko, A. V.

2010-01-01

We have built a wireless implantable microelectronic device for transmitting cortical signals transcutaneously. The device is aimed at interfacing a microelectrode array cortical to an external computer for neural control applications. Our implantable microsystem enables presently 16-channel broadband neural recording in a non-human primate brain by converting these signals to a digital stream of infrared light pulses for transmission through the skin. The implantable unit employs a flexible polymer substrate onto which we have integrated ultra-low power amplification with analog multiplexing, an analog-to-digital converter, a low power digital controller chip, and infrared telemetry. The scalable 16-channel microsystem can employ any of several modalities of power supply, including via radio frequency by induction, or infrared light via a photovoltaic converter. As of today, the implant has been tested as a sub-chronic unit in non-human primates (~ 1 month), yielding robust spike and broadband neural data on all available channels. PMID:19502132

Microfabrication, characterization and in vivo MRI compatibility of diamond microelectrodes array for neural interfacing.

PubMed

Hébert, Clément; Warnking, Jan; Depaulis, Antoine; Garçon, Laurie Amandine; Mermoux, Michel; Eon, David; Mailley, Pascal; Omnès, Franck

2015-01-01

Neural interfacing still requires highly stable and biocompatible materials, in particular for in vivo applications. Indeed, most of the currently used materials are degraded and/or encapsulated by the proximal tissue leading to a loss of efficiency. Here, we considered boron doped diamond microelectrodes to address this issue and we evaluated the performances of a diamond microelectrode array. We described the microfabrication process of the device and discuss its functionalities. We characterized its electrochemical performances by cyclic voltammetry and impedance spectroscopy in saline buffer and observed the typical diamond electrode electrochemical properties, wide potential window and low background current, allowing efficient electrochemical detection. The charge storage capacitance and the modulus of the electrochemical impedance were found to remain in the same range as platinum electrodes used for standard commercial devices. Finally we observed a reduced Magnetic Resonance Imaging artifact when the device was implanted on a rat cortex, suggesting that boron doped-diamond is a very promising electrode material allowing functional imaging. Copyright © 2014 Elsevier B.V. All rights reserved.

Estimation of neural energy in microelectrode signals

NASA Astrophysics Data System (ADS)

Gaumond, R. P.; Clement, R.; Silva, R.; Sander, D.

2004-09-01

We considered the problem of determining the neural contribution to the signal recorded by an intracortical electrode. We developed a linear least-squares approach to determine the energy fraction of a signal attributable to an arbitrary number of autocorrelation-defined signals buried in noise. Application of the method requires estimation of autocorrelation functions Rap(tgr) characterizing the action potential (AP) waveforms and Rn(tgr) characterizing background noise. This method was applied to the analysis of chronically implanted microelectrode signals from motor cortex of rat. We found that neural (AP) energy consisted of a large-signal component which grows linearly with the number of threshold-detected neural events and a small-signal component unrelated to the count of threshold-detected AP signals. The addition of pseudorandom noise to electrode signals demonstrated the algorithm's effectiveness for a wide range of noise-to-signal energy ratios (0.08 to 39). We suggest, therefore, that the method could be of use in providing a measure of neural response in situations where clearly identified spike waveforms cannot be isolated, or in providing an additional 'background' measure of microelectrode neural activity to supplement the traditional AP spike count.

In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes

PubMed Central

Harris, J P; Hess, A E; Rowan, S J; Weder, C; Zorman, C A; Tyler, D J; Capadona, J R

2012-01-01

We recently introduced a series of stimuli-responsive, mechanically-adaptive polymer nanocomposites. Here, we report the first application of these bio-inspired materials as substrates for intracortical microelectrodes. Our hypothesis is that the ideal electrode should be initially stiff to facilitate minimal trauma during insertion into the cortex, yet becomes mechanically compliant to match the stiffness of the brain tissue and minimize forces exerted on the tissue, attenuating inflammation. Microprobes created from mechanically reinforced nanocomposites demonstrated a significant advantage compared to model microprobes composed of neat polymer only. The nanocomposite microprobes exhibit a higher storage modulus (E’ = ~5 GPa) than the neat polymer microprobes (E’ = ~2 GPa) and could sustain higher loads (~17 mN), facilitating penetration through the pia mater and insertion into the cerebral cortex of a rat. In contrast, the neat polymer microprobes mechanically failed under lower loads (~7 mN) before they were capable of inserting into cortical tissue. Further, we demonstrated the material’s ability to morph while in the rat cortex to more closely match the mechanical properties of the cortical tissue. Nanocomposite microprobes that were implanted into the rat cortex for up to 8 weeks demonstrated increased cell density at the microelectrode-tissue interface and a lack of tissue necrosis or excessive gliosis. This body of work introduces our nanocomposite-based microprobes as adaptive substrates for intracortical microelectrodes and potentially other biomedical applications. PMID:21654037

Prolonged Stimulation of a Brainstem Raphe Region Attenuates Experimental Autoimmune Encephalomyelitis

PubMed Central

Madsen, Pernille M.; Sloley, Stephanie S.; Vitores, Alberto A.; Carballosa-Gautam, Melissa M.; Brambilla, Roberta; Hentall, Ian D.

2017-01-01

Multiple sclerosis (MS), a neuroinflammatory disease, has few treatment options, none entirely adequate. We studied whether prolonged electrical stimulation of a hindbrain region (the nucleus raphe magnus) can attenuate experimental autoimmune encephalomyelitis, a murine model of MS induced by MOG35-55 injection. Eight days after symptoms emerged, a wireless electrical stimulator with a connectorless protruding microelectrode was implanted cranially, and daily intermittent stimulation of awake, unrestrained mice began immediately. The thoracic spinal cord was analyzed for changes in histology (on day 29) and gene expression (on day 37), with a focus on myelination and cytokine production. Controls, with inactive implants, showed a phase of disease exacerbation on days 19–25 that stimulation for >16 days eliminated. Prolonged stimulation also reduced infiltrating immune cells and increased numbers of myelinated axons. It additionally lowered gene expression for some pro-inflammatory cytokines (interferon gamma and tumor necrosis factor) and for platelet-derived growth factor receptor alpha, a marker of oligodendrocyte precursors, while raising it for myelin basic protein. Restorative treatments for MS might profitably consider ways to stimulate the raphe magnus, directly or via its inputs, or to emulate its serotonergic and peptidergic output. PMID:28147248

Microelectrodes with Three-Dimensional Structures for Improved Neural Interfacing

DTIC Science & Technology

2001-10-25

highly xible bio-interfaces [2]. Polyimides combine excellent ectrical and mechanical characteristics with biocompatibility ], and are well known in...excellent biocompatibility , polyimide -based electrodes promise for fabrication of long-term implants for the use in prostheses. The flexible structures...R. R. Richardson, J. A. Miller, and W. M. Reichert, " Polyimides as Biomaterials - Preliminary Biocompatibility Testing," Biomaterials, vol. 14, pp

A modular robust control framework for control of movement elicited by multi-electrode intraspinal microstimulation

NASA Astrophysics Data System (ADS)

Roshani, Amir; Erfanian, Abbas

2016-08-01

Objective. An important issue in restoring motor function through intraspinal microstimulation (ISMS) is the motor control. To provide a physiologically plausible motor control using ISMS, it should be able to control the individual motor unit which is the lowest functional unit of motor control. By focal stimulation only a small group of motor neurons (MNs) within a motor pool can be activated. Different groups of MNs within a motor pool can potentially be activated without involving adjacent motor pools by local stimulation of different parts of a motor pool via microelectrode array implanted into a motor pool. However, since the system has multiple inputs with single output during multi-electrode ISMS, it poses a challenge to movement control. In this paper, we proposed a modular robust control strategy for movement control, whereas multi-electrode array is implanted into each motor activation pool of a muscle. Approach. The controller was based on the combination of proportional-integral-derivative and adaptive fuzzy sliding mode control. The global stability of the controller was guaranteed. Main results. The results of the experiments on rat models showed that the multi-electrode control can provide a more robust control and accurate tracking performance than a single-electrode control. The control output can be pulse amplitude (pulse amplitude modulation, PAM) or pulse width (pulse width modulation, PWM) of the stimulation signal. The results demonstrated that the controller with PAM provided faster convergence rate and better tracking performance than the controller with PWM. Significance. This work represents a promising control approach to the restoring motor functions using ISMS. The proposed controller requires no prior knowledge about the dynamics of the system to be controlled and no offline learning phase. The proposed control design is modular in the sense that each motor pool has an independent controller and each controller is able to control ISMS through an array of microelectrodes.

Polyethylenimine carbon nanotube fiber electrodes for enhanced detection of neurotransmitters.

PubMed

Zestos, Alexander G; Jacobs, Christopher B; Trikantzopoulos, Elefterios; Ross, Ashley E; Venton, B Jill

2014-09-02

Carbon nanotube (CNT)-based microelectrodes have been investigated as alternatives to carbon-fiber microelectrodes for the detection of neurotransmitters because they are sensitive, exhibit fast electron transfer kinetics, and are more resistant to surface fouling. Wet spinning CNTs into fibers using a coagulating polymer produces a thin, uniform fiber that can be fabricated into an electrode. CNT fibers formed in poly(vinyl alcohol) (PVA) have been used as microelectrodes to detect dopamine, serotonin, and hydrogen peroxide. In this study, we characterize microelectrodes with CNT fibers made in polyethylenimine (PEI), which have much higher conductivity than PVA-CNT fibers. PEI-CNT fibers have lower overpotentials and higher sensitivities than PVA-CNT fiber microelectrodes, with a limit of detection of 5 nM for dopamine. The currents for dopamine were adsorption controlled at PEI-CNT fiber microelectrodes, independent of scan repetition frequency, and stable for over 10 h. PEI-CNT fiber microelectrodes were resistant to surface fouling by serotonin and the metabolite interferant 5-hydroxyindoleacetic acid (5-HIAA). No change in sensitivity was observed for detection of serotonin after 30 flow injection experiments or after 2 h in 5-HIAA for PEI-CNT electrodes. The antifouling properties were maintained in brain slices when serotonin was exogenously applied multiple times or after bathing the slice in 5-HIAA. Thus, PEI-CNT fiber electrodes could be useful for the in vivo monitoring of neurochemicals.

Recording nerve signals in canine sciatic nerves with a flexible penetrating microelectrode array

NASA Astrophysics Data System (ADS)

Byun, Donghak; Cho, Sung-Joon; Lee, Byeong Han; Min, Joongkee; Lee, Jong-Hyun; Kim, Sohee

2017-08-01

Objective. Previously, we presented the fabrication and characterization of a flexible penetrating microelectrode array (FPMA) as a neural interface device. In the present study, we aim to prove the feasibility of the developed FPMA as a chronic intrafascicular recording tool for peripheral applications. Approach. For recording from the peripheral nerves of medium-sized animals, the FPMA was integrated with an interconnection cable and other parts that were designed to fit canine sciatic nerves. The uniformity of tip exposure and in vitro electrochemical properties of the electrodes were characterized. The capability of the device to acquire in vivo electrophysiological signals was evaluated by implanting the FPMA assembly in canine sciatic nerves acutely as well as chronically for 4 weeks. We also examined the histology of implanted tissues to evaluate the damage caused by the device. Main results. Throughout recording sessions, we observed successful multi-channel recordings (up to 73% of viable electrode channels) of evoked afferent and spontaneous nerve unit spikes with high signal quality (SNR  >  4.9). Also, minor influences of the device implantation on the morphology of nerve tissues were found. Significance. The presented results demonstrate the viability of the developed FPMA device in the peripheral nerves of medium-sized animals, thereby bringing us a step closer to human applications. Furthermore, the obtained data provide a driving force toward a further study for device improvements to be used as a bidirectional neural interface in humans.

A method and technical equipment for an acute human trial to evaluate retinal implant technology

NASA Astrophysics Data System (ADS)

Hornig, Ralf; Laube, Thomas; Walter, Peter; Velikay-Parel, Michaela; Bornfeld, Norbert; Feucht, Matthias; Akguel, Harun; Rössler, Gernot; Alteheld, Nils; Lütke Notarp, Dietmar; Wyatt, John; Richard, Gisbert

2005-03-01

This paper reports on methods and technical equipment to investigate the epiretinal stimulation of the retina in blind human subjects in acute trials. Current is applied to the retina through a thin, flexible microcontact film (microelectrode array) with electrode diameters ranging from 50 to 360 µm. The film is mounted in a custom-designed surgical tool that is hand-held by the surgeon during stimulation. The eventual goal of the work is the development of a chronically implantable retinal prosthesis to restore a useful level of vision to patients who are blind with outer retinal degenerations, specifically retinitis pigmentosa and macular degeneration.

Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates

NASA Astrophysics Data System (ADS)

Barrese, James C.; Aceros, Juan; Donoghue, John P.

2016-04-01

Objective. Signal attenuation is a major problem facing intracortical sensors for chronic neuroprosthetic applications. Many studies suggest that failure is due to gliosis around the electrode tips, however, mechanical and material causes of failure are often overlooked. The purpose of this study was to investigate the factors contributing to progressive signal decline by using scanning electron microscopy (SEM) to visualize structural changes in chronically implanted arrays and histology to examine the tissue response at corresponding implant sites. Approach. We examined eight chronically implanted intracortical microelectrode arrays (MEAs) explanted from non-human primates at times ranging from 37 to 1051 days post-implant. We used SEM, in vivo neural recordings, and histology (GFAP, Iba-1, NeuN). Three MEAs that were never implanted were also imaged as controls. Main results. SEM revealed progressive corrosion of the platinum electrode tips and changes to the underlying silicon. The parylene insulation was prone to cracking and delamination, and in some instances the silicone elastomer also delaminated from the edges of the MEA. Substantial tissue encapsulation was observed and was often seen growing into defects in the platinum and parylene. These material defects became more common as the time in vivo increased. Histology at 37 and 1051 days post-implant showed gliosis, disruption of normal cortical architecture with minimal neuronal loss, and high Iba-1 reactivity, especially within the arachnoid and dura. Electrode tracts were either absent or barely visible in the cortex at 1051 days, but were seen in the fibrotic encapsulation material suggesting that the MEAs were lifted out of the brain. Neural recordings showed a progressive drop in impedance, signal amplitude, and viable channels over time. Significance. These results provide evidence that signal loss in MEAs is truly multifactorial. Gliosis occurs in the first few months after implantation but does not prevent useful recordings for several years. Progressive meningeal fibrosis encapsulates and lifts MEAs out of the cortex while ongoing foreign body reactions lead to progressive degradation of the materials. Long-term impedance drops are due to the corrosion of platinum, cracking and delamination of parylene, and delamination of silicone elastomer. Oxygen radicals released by cells of the immune system likely mediate the degradation of these materials. Future MEA designs must address these problems through more durable insulation materials, more inert electrode alloys, and pharmacologic suppression of fibroblasts and leukocytes.

Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates

PubMed Central

Barrese, James C; Aceros, Juan; Donoghue, John P

2016-01-01

Objective Signal attenuation is a major problem facing intracortical sensors for chronic neuroprosthetic applications. Many studies suggest that failure is due to gliosis around the electrode tips, however, mechanical and material causes of failure are often overlooked. The purpose of this study was to investigate the factors contributing to progressive signal decline by using scanning electron microscopy (SEM) to visualize structural changes in chronically implanted arrays and histology to examine the tissue response at corresponding implant sites. Approach We examined eight chronically implanted intracortical microelectrode arrays (MEAs) explanted from non-human primates at times ranging from 37 to 1051 days post-implant. We used SEM, in vivo neural recordings, and histology (GFAP, Iba-1, NeuN). Three MEAs that were never implanted were also imaged as controls. Main results SEM revealed progressive corrosion of the platinum electrode tips and changes to the underlying silicon. The parylene insulation was prone to cracking and delamination, and in some instances the silicone elastomer also delaminated from the edges of the MEA. Substantial tissue encapsulation was observed and was often seen growing into defects in the platinum and parylene. These material defects became more common as the time in vivo increased. Histology at 37 and 1051 days post-implant showed gliosis, disruption of normal cortical architecture with minimal neuronal loss, and high Iba-1 reactivity, especially within the arachnoid and dura. Electrode tracts were either absent or barely visible in the cortex at 1051 days, but were seen in the fibrotic encapsulation material suggesting that the MEAs were lifted out of the brain. Neural recordings showed a progressive drop in impedance, signal amplitude, and viable channels over time. Significance These results provide evidence that signal loss in MEAs is truly multifactorial. Gliosis occurs in the first few months after implantation but does not prevent useful recordings for several years. Progressive meningeal fibrosis encapsulates and lifts MEAs out of the cortex while ongoing foreign body reactions lead to progressive degradation of the materials. Long-term impedance drops are due to the corrosion of platinum, cracking and delamination of parylene, and delamination of silicone elastomer. Oxygen radicals released by cells of the immune system likely mediate the degradation of these materials. Future MEA designs must address these problems through more durable insulation materials, more inert electrode alloys, and pharmacologic suppression of fibroblasts and leukocytes. PMID:26824680

Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates.

PubMed

Barrese, James C; Aceros, Juan; Donoghue, John P

2016-04-01

Signal attenuation is a major problem facing intracortical sensors for chronic neuroprosthetic applications. Many studies suggest that failure is due to gliosis around the electrode tips, however, mechanical and material causes of failure are often overlooked. The purpose of this study was to investigate the factors contributing to progressive signal decline by using scanning electron microscopy (SEM) to visualize structural changes in chronically implanted arrays and histology to examine the tissue response at corresponding implant sites. We examined eight chronically implanted intracortical microelectrode arrays (MEAs) explanted from non-human primates at times ranging from 37 to 1051 days post-implant. We used SEM, in vivo neural recordings, and histology (GFAP, Iba-1, NeuN). Three MEAs that were never implanted were also imaged as controls. SEM revealed progressive corrosion of the platinum electrode tips and changes to the underlying silicon. The parylene insulation was prone to cracking and delamination, and in some instances the silicone elastomer also delaminated from the edges of the MEA. Substantial tissue encapsulation was observed and was often seen growing into defects in the platinum and parylene. These material defects became more common as the time in vivo increased. Histology at 37 and 1051 days post-implant showed gliosis, disruption of normal cortical architecture with minimal neuronal loss, and high Iba-1 reactivity, especially within the arachnoid and dura. Electrode tracts were either absent or barely visible in the cortex at 1051 days, but were seen in the fibrotic encapsulation material suggesting that the MEAs were lifted out of the brain. Neural recordings showed a progressive drop in impedance, signal amplitude, and viable channels over time. These results provide evidence that signal loss in MEAs is truly multifactorial. Gliosis occurs in the first few months after implantation but does not prevent useful recordings for several years. Progressive meningeal fibrosis encapsulates and lifts MEAs out of the cortex while ongoing foreign body reactions lead to progressive degradation of the materials. Long-term impedance drops are due to the corrosion of platinum, cracking and delamination of parylene, and delamination of silicone elastomer. Oxygen radicals released by cells of the immune system likely mediate the degradation of these materials. Future MEA designs must address these problems through more durable insulation materials, more inert electrode alloys, and pharmacologic suppression of fibroblasts and leukocytes.

Ultrasoft microwire neural electrodes improve chronic tissue integration

PubMed Central

Du, Zhanhong Jeff; Kolarcik, Christi L.; Kozai, Takashi D.Y.; Luebben, Silvia D.; Sapp, Shawn A.; Zheng, Xin Sally; Nabity, James A.; Cui, X. Tracy

2017-01-01

Chronically implanted neural multi-electrode arrays (MEA) are an essential technology for recording electrical signals from neurons and/or modulating neural activity through stimulation. However, current MEAs, regardless of the type, elicit an inflammatory response that ultimately leads to device failure. Traditionally, rigid materials like tungsten and silicon have been employed to interface with the relatively soft neural tissue. The large stiffness mismatch is thought to exacerbate the inflammatory response. In order to minimize the disparity between the device and the brain, we fabricated novel ultrasoft electrodes consisting of elastomers and conducting polymers with mechanical properties much more similar to those of brain tissue than previous neural implants. In this study, these ultrasoft microelectrodes were inserted and released using a stainless steel shuttle with polyethyleneglycol (PEG) glue. The implanted microwires showed functionality in acute neural stimulation. When implanted for 1 or 8 weeks, the novel soft implants demonstrated significantly reduced inflammatory tissue response at week 8 compared to tungsten wires of similar dimension and surface chemistry. Furthermore, a higher degree of cell body distortion was found next to the tungsten implants compared to the polymer implants. Our results support the use of these novel ultrasoft electrodes for long term neural implants. PMID:28185910

Abiotic-biotic characterization of Pt/Ir microelectrode arrays in chronic implants

PubMed Central

Prasad, Abhishek; Xue, Qing-Shan; Dieme, Robert; Sankar, Viswanath; Mayrand, Roxanne C.; Nishida, Toshikazu; Streit, Wolfgang J.; Sanchez, Justin C.

2014-01-01

Pt/Ir electrodes have been extensively used in neurophysiology research in recent years as they provide a more inert recording surface as compared to tungsten or stainless steel. While floating microelectrode arrays (FMA) consisting of Pt/Ir electrodes are an option for neuroprosthetic applications, long-term in vivo functional performance characterization of these FMAs is lacking. In this study, we have performed comprehensive abiotic-biotic characterization of Pt/Ir arrays in 12 rats with implant periods ranging from 1 week up to 6 months. Each of the FMAs consisted of 16-channel, 1.5 mm long, and 75 μm diameter microwires with tapered tips that were implanted into the somatosensory cortex. Abiotic characterization included (1) pre-implant and post-explant scanning electron microscopy (SEM) to study recording site changes, insulation delamination and cracking, and (2) chronic in vivo electrode impedance spectroscopy. Biotic characterization included study of microglial responses using a panel of antibodies, such as Iba1, ED1, and anti-ferritin, the latter being indicative of blood-brain barrier (BBB) disruption. Significant structural variation was observed pre-implantation among the arrays in the form of irregular insulation, cracks in insulation/recording surface, and insulation delamination. We observed delamination and cracking of insulation in almost all electrodes post-implantation. These changes altered the electrochemical surface area of the electrodes and resulted in declining impedance over the long-term due to formation of electrical leakage pathways. In general, the decline in impedance corresponded with poor electrode functional performance, which was quantified via electrode yield. Our abiotic results suggest that manufacturing variability and insulation material as an important factor contributing to electrode failure. Biotic results show that electrode performance was not correlated with microglial activation (neuroinflammation) as we were able to observe poor performance in the absence of neuroinflammation, as well as good performance in the presence of neuroinflammation. One biotic change that correlated well with poor electrode performance was intraparenchymal bleeding, which was evident macroscopically in some rats and presented microscopically by intense ferritin immunoreactivity in microglia/macrophages. Thus, we currently consider intraparenchymal bleeding, suboptimal electrode fabrication, and insulation delamination as the major factors contributing toward electrode failure. PMID:24550823

Microfabrication of an Implantable silicone Microelectrode array for an epiretinal prosthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maghribi, Mariam Nader

2003-06-10

Millions of people suffering from diseases such as retinitis pigmentosa and macular degeneration are legally blind due to the loss of photoreceptor function. Fortunately a large percentage of the neural cells connected to the photoreceptors remain viable, and electrical stimulation of these cells has been shown to result in visual perception. These findings have generated worldwide efforts to develop a retinal prosthesis device, with the hope of restoring vision. Advances in microfabrication, integrated circuits, and wireless technologies provide the means to reach this challenging goal. This dissertation describes the development of innovative silicone-based microfabrication techniques for producing an implantable microelectrodemore » array. The microelectrode array is a component of an epiretinal prosthesis being developed by a multi-laboratory consortium. This array will serve as the interface between an electronic imaging system and the human eye, directly stimulating retinal neurons via thin film conducting traces. Because the array is intended as a long-term implant, vital biological and physical design requirements must be met. A retinal implant poses difficult engineering challenges due to the size of the intraocular cavity and the delicate retina. Not only does it have to be biocompatible in terms of cytotoxicity and degradation, but it also has to be structurally biocompatible, with regard to smooth edges and high conformability; basically mimicking the biological tissue. This is vital to minimize stress and prevent physical damage to the retina. Also, the device must be robust to withstand the forces imposed on it during fabrication and implantation. In order to meet these biocompatibility needs, the use of non-conventional microfabrication materials such as silicone is required. This mandates the enhancement of currently available polymer-based fabrication techniques and the development of new microfabrication methods. Through an iterative process, devices were designed, fabricated, tested and implanted into a canine eye. Metal traces were embedded within a thin substrate fabricated using poly (dimethyl siloxane) (PDMS), an inert biocompatible elastomeric material with high oxygen permeability and low water permeability. Due to its highly conformable nature, PDMS contacted the curved retinal surface uniformly. Fundamental material characteristics were examined to develop reliable and repeatable fabrication processes.« less

Encoding of the amplitude modulation of pulsatile electrical stimulation in the feline cochlear nucleus by neurons in the inferior colliculus; effects of stimulus pulse rate

NASA Astrophysics Data System (ADS)

McCreery, Douglas; Han, Martin; Pikov, Victor; Yadav, Kamal; Pannu, Satinderpall

2013-10-01

Objectives. Persons without a functional auditory nerve cannot benefit from cochlear implants, but some hearing can be restored by an auditory brainstem implant (ABI) with stimulating electrodes implanted on the surface of the cochlear nucleus (CN). Most users benefit from their ABI, but speech recognition tends to be poorer than for users of cochlear implants. Psychophysical studies suggest that poor modulation detection may contribute to the limited performance of ABI users. In a cat model, we determined how the pulse rate of the electrical stimulus applied within or on the CN affects temporal and rate encoding of amplitude modulation (AM) by neurons in the central nucleus of the inferior colliculus (ICC). Approach. Stimulating microelectrodes were implanted chronically in and on the cats' CN, and multi-site recording microelectrodes were implanted chronically into the ICC. Encoding of AM pulse trains by neurons in the ICC was characterized as vector strength (VS), the synchrony of neural activity with the AM, and as the mean rate of neuronal action potentials (neuronal spike rate (NSR)). Main results. For intranuclear microstimulation, encoding of AM as VS was up to 3 dB greater when stimulus pulse rate was increased from 250 to 500 pps, but only for neuronal units with low best acoustic frequencies, and when the electrical stimulation was modulated at low frequencies (10-20 Hz). For stimulation on the surface of the CN, VS was similar at 250 and 500 pps, and the dynamic range of the VS was reduced for pulse rates greater than 250 pps. Modulation depth was encoded strongly as VS when the maximum stimulus amplitude was held constant across a range of modulation depth. This ‘constant maximum’ protocol allows enhancement of modulation depth while preserving overall dynamic range. However, modulation depth was not encoded as strongly as NSR. Significance. The findings have implications for improved sound processors for present and future ABIs. The performance of ABIs may benefit from using pulse rates greater than those presently used in most ABIs, and by sound processing strategies that enhance the modulation depth of the electrical stimulus while preserving dynamic range.

Using Arrays of Microelectrodes Implanted in Residual Peripheral Nerves to Provide Dextrous Control of, and Modulated Sensory Feedback from, a Hand Prosthesis

DTIC Science & Technology

2015-10-01

Modulated Sensory Feedback from, a Hand Prosthesis PRINCIPAL INVESTIGATOR: Bradley Greger, PhD CONTRACTING ORGANIZATION: Arizona State University...Residual Peripheral Nerves to Provide Dextrous Control of, and Modulated Sensory Feedback from, a Hand Prosthesis 5a. CONTRACT NUMBER 5b. GRANT...Peripheral Nerve Interface, Prosthetic Hand, Neural Prosthesis , Sensory Feedback, Micro-stimulation, Electrophysiology, Action Potentials, Micro

Listening to Brain Microcircuits for Interfacing With External World—Progress in Wireless Implantable Microelectronic Neuroengineering Devices

PubMed Central

Nurmikko, Arto V.; Donoghue, John P.; Hochberg, Leigh R.; Patterson, William R.; Song, Yoon-Kyu; Bull, Christopher W.; Borton, David A.; Laiwalla, Farah; Park, Sunmee; Ming, Yin; Aceros, Juan

2011-01-01

Acquiring neural signals at high spatial and temporal resolution directly from brain microcircuits and decoding their activity to interpret commands and/or prior planning activity, such as motion of an arm or a leg, is a prime goal of modern neurotechnology. Its practical aims include assistive devices for subjects whose normal neural information pathways are not functioning due to physical damage or disease. On the fundamental side, researchers are striving to decipher the code of multiple neural microcircuits which collectively make up nature’s amazing computing machine, the brain. By implanting biocompatible neural sensor probes directly into the brain, in the form of microelectrode arrays, it is now possible to extract information from interacting populations of neural cells with spatial and temporal resolution at the single cell level. With parallel advances in application of statistical and mathematical techniques tools for deciphering the neural code, extracted populations or correlated neurons, significant understanding has been achieved of those brain commands that control, e.g., the motion of an arm in a primate (monkey or a human subject). These developments are accelerating the work on neural prosthetics where brain derived signals may be employed to bypass, e.g., an injured spinal cord. One key element in achieving the goals for practical and versatile neural prostheses is the development of fully implantable wireless microelectronic “brain-interfaces” within the body, a point of special emphasis of this paper. PMID:21654935

Electrochemical quantification of serotonin in the live embryonic zebrafish intestine

PubMed Central

Njagi, John; Ball, Michael; Best, Marc; Wallace, Kenneth N.; Andreescu, Silvana

2010-01-01

We monitored real-time in vivo levels of serotonin release in the digestive system of intact zebrafish embryos during early development (5 dpf) using differential pulse voltammetry with implanted carbon fiber microelectrodes modified with carbon nanotubes dispersed in nafion. A detection limit of 1 nM, a linear range between 5 to 200 nM and a sensitivity of 83.65 nA·μM−1 were recorded. The microelectrodes were implanted at various locations in the intestine of zebrafish embryos. Serotonin levels of up to 29.9(±1.13) nM were measured in vivo in normal physiological conditions. Measurements were performed in intact live embryos without additional perturbation beyond electrode insertion. The sensor was able to quantify pharmacological alterations in serotonin release and provide the longitudinal distribution of this neurotransmitter along the intestine with high spatial resolution. In the presence of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), concentrations of 54.1(±1.05) nM were recorded while in the presence of p-chloro-phenylalanine (PCPA), a tryptophan hydroxylase inhibitor, the serotonin levels decreased to 7.2(±0.45) nM. The variation of serotonin levels was correlated with immunohistochemical analysis. We have demonstrated the first use of electrochemical microsensors for in vivo monitoring of intestinal serotonin levels in intact zebrafish embryos. PMID:20148518

Development of Cu nanoflowers modified the flexible needle-type microelectrode and its application in continuous monitoring glucose in vivo.

PubMed

Fang, Yuxin; Wang, Shenjun; Liu, Yangyang; Xu, Zhifang; Zhang, Kuo; Guo, Yi

2018-07-01

A minimally invasive glucose microbiosensor based the flexibly integrated electrode for continuous monitoring glucose in vivo has been developed in this study. This was achieved by coating needle-type microelectrode with Cu nanoflowers, nafion, glucose oxidase (GOD) and polyurethane (PU) membranes, successfully prepared with layer-by-layer deposition. The Cu nanomaterials provided a large specific surface area and electrocatalytic activity for glucose detection. The PU layers as mass-transport limiting membranes significantly enhanced the linearity and stability of sensors. The resulting biosensor exhibited a wide linear range of 0-20 mM, with a good sensitivity of 42.38 nA mM -1 (correlation coefficient r 2 was 0.99) and a fast response time of less than 15 s. In vivo implantable experiments using anesthetized rats showed excellent real-time response to the variation of blood glucose concentration. And the variation tendency of sensor output was consistent with that using the glucose meter. Overall, the results supported the suitability of this microsensor for measuring rapid changes of glucose in vivo. This work offers a promising approach in implantable device applications related to diabetes management as well as other medical diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Decoding grating orientation from microelectrode array recordings in monkey cortical area V4.

PubMed

Manyakov, Nikolay V; Van Hulle, Marc M

2010-04-01

We propose an invasive brain-machine interface (BMI) that decodes the orientation of a visual grating from spike train recordings made with a 96 microelectrodes array chronically implanted into the prelunate gyrus (area V4) of a rhesus monkey. The orientation is decoded irrespective of the grating's spatial frequency. Since pyramidal cells are less prominent in visual areas, compared to (pre)motor areas, the recordings contain spikes with smaller amplitudes, compared to the noise level. Hence, rather than performing spike decoding, feature selection algorithms are applied to extract the required information for the decoder. Two types of feature selection procedures are compared, filter and wrapper. The wrapper is combined with a linear discriminant analysis classifier, and the filter is followed by a radial-basis function support vector machine classifier. In addition, since we have a multiclass classification problen, different methods for combining pairwise classifiers are compared.

Continuous Force Decoding from Local Field Potentials of the Primary Motor Cortex in Freely Moving Rats.

PubMed

Khorasani, Abed; Heydari Beni, Nargess; Shalchyan, Vahid; Daliri, Mohammad Reza

2016-10-21

Local field potential (LFP) signals recorded by intracortical microelectrodes implanted in primary motor cortex can be used as a high informative input for decoding of motor functions. Recent studies show that different kinematic parameters such as position and velocity can be inferred from multiple LFP signals as precisely as spiking activities, however, continuous decoding of the force magnitude from the LFP signals in freely moving animals has remained an open problem. Here, we trained three rats to press a force sensor for getting a drop of water as a reward. A 16-channel micro-wire array was implanted in the primary motor cortex of each trained rat, and obtained LFP signals were used for decoding of the continuous values recorded by the force sensor. Average coefficient of correlation and the coefficient of determination between decoded and actual force signals were r = 0.66 and R 2  = 0.42, respectively. We found that LFP signal on gamma frequency bands (30-120 Hz) had the most contribution in the trained decoding model. This study suggests the feasibility of using low number of LFP channels for the continuous force decoding in freely moving animals resembling BMI systems in real life applications.

Acute in vivo testing of a conformal polymer microelectrode array for multi-region hippocampal recordings

NASA Astrophysics Data System (ADS)

Xu, Huijing; Weltman Hirschberg, Ahuva; Scholten, Kee; Berger, Theodore William; Song, Dong; Meng, Ellis

2018-02-01

Objective. The success of a cortical prosthetic device relies upon its ability to attain resolvable spikes from many neurons in particular neural networks over long periods of time. Traditionally, lifetimes of neural recordings are greatly limited by the body’s immune response against the foreign implant which causes neuronal death and glial scarring. This immune reaction is posited to be exacerbated by micromotion between the implant, which is often rigid, and the surrounding, soft brain tissue, and attenuates the quality of recordings over time. Approach. In an attempt to minimize the foreign body response to a penetrating neural array that records from multiple brain regions, Parylene C, a flexible, biocompatible polymer was used as the substrate material for a functional, proof-of-concept neural array with a reduced elastic modulus. This probe array was designed and fabricated to have 64 electrodes positioned to match the anatomy of the rat hippocampus and allow for simultaneous recordings between two cell-body layers of interest. A dissolvable brace was used for deep-brain penetration of the flexible array. Main results. Arrays were electrochemically characterized at the benchtop, and a novel insertion technique that restricts acute insertion injury enabled accurate target placement of four, bare, flexible arrays to greater than 4 mm deep into the rat brain. Arrays were tested acutely and in vivo recordings taken intra-operatively reveal spikes in both targeted regions of the hippocampus with spike amplitudes and noise levels similar to those recorded with microwires. Histological staining of a sham array implanted for one month reveals limited astrocytic scarring and neuronal death around the implant. Significance. This work represents one of the first examples of a penetrating polymer probe array that records from individual neurons in structures that lie deep within the brain.

A silicon-based microelectrode array with a microdrive for monitoring brainstem regions of freely moving rats

NASA Astrophysics Data System (ADS)

Márton, G.; Baracskay, P.; Cseri, B.; Plósz, B.; Juhász, G.; Fekete, Z.; Pongrácz, A.

2016-04-01

Objective. Exploring neural activity behind synchronization and time locking in brain circuits is one of the most important tasks in neuroscience. Our goal was to design and characterize a microelectrode array (MEA) system specifically for obtaining in vivo extracellular recordings from three deep-brain areas of freely moving rats, simultaneously. The target areas, the deep mesencephalic reticular-, pedunculopontine tegmental- and pontine reticular nuclei are related to the regulation of sleep-wake cycles. Approach. The three targeted nuclei are collinear, therefore a single-shank MEA was designed in order to contact them. The silicon-based device was equipped with 3*4 recording sites, located according to the geometry of the brain regions. Furthermore, a microdrive was developed to allow fine actuation and post-implantation relocation of the probe. The probe was attached to a rigid printed circuit board, which was fastened to the microdrive. A flexible cable was designed in order to provide not only electronic connection between the probe and the amplifier system, but sufficient freedom for the movements of the probe as well. Main results. The microdrive was stable enough to allow precise electrode targeting into the tissue via a single track. The microelectrodes on the probe were suitable for recording neural activity from the three targeted brainstem areas. Significance. The system offers a robust solution to provide long-term interface between an array of precisely defined microelectrodes and deep-brain areas of a behaving rodent. The microdrive allowed us to fine-tune the probe location and easily scan through the regions of interest.

Ceramic-based microelectrode arrays: recording surface characteristics and topographical analysis

PubMed Central

Talauliker, Pooja M.; Price, David A.; Burmeister, Jason J.; Nagari, Silpa; Quintero, Jorge E.; Pomerleau, Francois; Huettl, Peter; Hastings, J. Todd; Gerhardt, Greg A.

2011-01-01

Amperometric measurements using microelectrode arrays (MEAs) provide spatially and temporally resolved measures of neuromolecules in the central nervous system of rats, mice and non-human primates. Multi-site MEAs can be mass fabricated on ceramic (Al2O3) substrate using photolithographic methods, imparting a high level of precision and reproducibility in a rigid but durable recording device. Although the functional capabilities of MEAs have been previously documented for both anesthetized and freely-moving paradigms, the performance enabling intrinsic physical properties of the MEA device have not heretofore been presented. In these studies, spectral analysis confirmed that the MEA recording sites were primarily composed of elemental platinum (Pt°). In keeping with the precision of the photolithographic process, scanning electron microscopy revealed that the Pt recording sites have unique microwell geometries post-fabrication. Atomic force microscopy demonstrated that the recording surfaces have nanoscale irregularities in the form of elevations and depressions, which contribute to increased current per unit area that exceeds previously reported microelectrode designs. The ceramic substrate on the back face of the MEA was characterized by low nanoscale texture and the ceramic sides consisted of an extended network of ridges and cavities. Thus, individual recording sites have a unique Pt° composition and surface profile that has not been previously observed for Pt-based microelectrodes. These features likely impact the physical chemistry of the device, which may influence adhesion of biological molecules and tissue as well as electrochemical recording performance post-implantation. This study is a necessary step towards understanding and extending the performance abilities of MEAs in vivo. PMID:21513736

In vivo optical modulation of neural signals using monolithically integrated two-dimensional neural probe arrays

PubMed Central

Son, Yoojin; Jenny Lee, Hyunjoo; Kim, Jeongyeon; Shin, Hyogeun; Choi, Nakwon; Justin Lee, C.; Yoon, Eui-Sung; Yoon, Euisik; Wise, Kensall D.; Geun Kim, Tae; Cho, Il-Joo

2015-01-01

Integration of stimulation modalities (e.g. electrical, optical, and chemical) on a large array of neural probes can enable an investigation of important underlying mechanisms of brain disorders that is not possible through neural recordings alone. Furthermore, it is important to achieve this integration of multiple functionalities in a compact structure to utilize a large number of the mouse models. Here we present a successful optical modulation of in vivo neural signals of a transgenic mouse through our compact 2D MEMS neural array (optrodes). Using a novel fabrication method that embeds a lower cladding layer in a silicon substrate, we achieved a thin silicon 2D optrode array that is capable of delivering light to multiple sites using SU-8 as a waveguide core. Without additional modification to the microelectrodes, the measured impedance of the multiple microelectrodes was below 1 MΩ at 1 kHz. In addition, with a low background noise level (±25 μV), neural spikes from different individual neurons were recorded on each microelectrode. Lastly, we successfully used our optrodes to modulate the neural activity of a transgenic mouse through optical stimulation. These results demonstrate the functionality of the 2D optrode array and its potential as a next-generation tool for optogenetic applications. PMID:26494437

A PDMS-Based Conical-Well Microelectrode Array for Surface Stimulation and Recording of Neural Tissues

PubMed Central

Guo, Liang; Meacham, Kathleen W.; Hochman, Shawn

2012-01-01

A method for fabricating polydimethylsiloxane (PDMS)-based microelectrode arrays (MEAs) featuring novel conical-well microelectrodes is described. The fabrication technique is reliable and efficient, and facilitates controllability over both the depth and the slope of the conical wells. Because of the high PDMS elasticity (as compared to other MEA substrate materials), this type of compliant MEA is promising for acute and chronic implantation in applications that benefit from conformable device contact with biological tissue surfaces and from minimal tissue damage. The primary advantage of the conical-well microelectrodes—when compared to planar electrodes—is that they provide an improved contact on tissue surface, which potentially provides isolation of the electrode microenvironment for better electrical interfacing. The raised wells increase the uniformity of current density distributions at both the electrode and tissue surfaces, and they also protect the electrode material from mechanical damage (e.g. from rubbing against the tissue). Using this technique, electrodes have been fabricated with diameters as small as 10µm and arrays have been fabricated with center-to-center electrode spacings of 60µm. Experimental results are presented, describing electrode-profile characterization, electrode-impedance measurement, and MEA-performance evaluation on fiber bundle recruitment in spinal cord white matter. PMID:20550983

Histological Evaluation of a Chronically-implanted Electrocorticographic Electrode Grid in a Non-human Primate

PubMed Central

Degenhart, Alan D.; Eles, James; Dum, Richard; Mischel, Jessica L.; Smalianchuk, Ivan; Endler, Bridget; Ashmore, Robin C.; Tyler-Kabara, Elizabeth C.; Hatsopoulos, Nicholas G.; Wang, Wei; Batista, Aaron P.; Cui, X. Tracy

2016-01-01

Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BMIs), potentially allows for field potentials to be recorded from the surface of the cerebral cortex for long durations without suffering the host-tissue reaction to the extent that it is common with intracortical microelectrodes. Though the stability of signals obtained from chronically-implanted ECoG electrodes has begun receiving attention, to date little work has characterized the effects of long-term implantation of ECoG electrodes on underlying cortical tissue. We implanted a high-density ECoG electrode grid subdurally over cortical motor areas of a Rhesus macaque for 666 days. Histological analysis revealed minimal damage to the cortex underneath the implant, though the grid itself was encapsulated in collagenous tissue. We observed macrophages and foreign body giant cells at the tissue-array interface, indicative of a stereotypical foreign body response. Despite this encapsulation, cortical modulation during reaching movements was observed more than 18 months post-implantation. These results suggest that ECoG may provide a means by which stable chronic cortical recordings can be obtained with comparatively little tissue damage, facilitating the development of clinically-viable brain-machine interface systems. PMID:27351722

Histological evaluation of a chronically-implanted electrocorticographic electrode grid in a non-human primate

NASA Astrophysics Data System (ADS)

Degenhart, Alan D.; Eles, James; Dum, Richard; Mischel, Jessica L.; Smalianchuk, Ivan; Endler, Bridget; Ashmore, Robin C.; Tyler-Kabara, Elizabeth C.; Hatsopoulos, Nicholas G.; Wang, Wei; Batista, Aaron P.; Cui, X. Tracy

2016-08-01

Objective. Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BMIs), potentially allows for field potentials to be recorded from the surface of the cerebral cortex for long durations without suffering the host-tissue reaction to the extent that it is common with intracortical microelectrodes. Though the stability of signals obtained from chronically implanted ECoG electrodes has begun receiving attention, to date little work has characterized the effects of long-term implantation of ECoG electrodes on underlying cortical tissue. Approach. We implanted and recorded from a high-density ECoG electrode grid subdurally over cortical motor areas of a Rhesus macaque for 666 d. Main results. Histological analysis revealed minimal damage to the cortex underneath the implant, though the grid itself was encapsulated in collagenous tissue. We observed macrophages and foreign body giant cells at the tissue-array interface, indicative of a stereotypical foreign body response. Despite this encapsulation, cortical modulation during reaching movements was observed more than 18 months post-implantation. Significance. These results suggest that ECoG may provide a means by which stable chronic cortical recordings can be obtained with comparatively little tissue damage, facilitating the development of clinically viable BMI systems.

In vivo Characterization of Amorphous Silicon Carbide As a Biomaterial for Chronic Neural Interfaces

PubMed Central

Knaack, Gretchen L.; McHail, Daniel G.; Borda, German; Koo, Beomseo; Peixoto, Nathalia; Cogan, Stuart F.; Dumas, Theodore C.; Pancrazio, Joseph J.

2016-01-01

Implantable microelectrode arrays (MEAs) offer clinical promise for prosthetic devices by enabling restoration of communication and control of artificial limbs. While proof-of-concept recordings from MEAs have been promising, work in animal models demonstrates that the obtained signals degrade over time. Both material robustness and tissue response are acknowledged to have a role in device lifetime. Amorphous Silicon carbide (a-SiC), a robust material that is corrosion resistant, has emerged as an alternative encapsulation layer for implantable devices. We systematically examined the impact of a-SiC coating on Si probes by immunohistochemical characterization of key markers implicated in tissue-device response. After implantation, we performed device capture immunohistochemical labeling of neurons, astrocytes, and activated microglia/macrophages after 4 and 8 weeks of implantation. Neuron loss and microglia activation were similar between Si and a-SiC coated probes, while tissue implanted with a-SiC displayed a reduction in astrocytes adjacent to the probe. These results suggest that a-SiC has a similar biocompatibility profile as Si, and may be suitable for implantable MEA applications as a hermetic coating to prevent material degradation. PMID:27445672

Neurobiochemical changes in the vicinity of a nanostructured neural implant

NASA Astrophysics Data System (ADS)

Bérces, Zsófia; Tóth, Kinga; Márton, Gergely; Pál, Ildikó; Kováts-Megyesi, Bálint; Fekete, Zoltán; Ulbert, István; Pongrácz, Anita

2016-10-01

Neural interface technologies including recording and stimulation electrodes are currently in the early phase of clinical trials aiming to help patients with spinal cord injuries, degenerative disorders, strokes interrupting descending motor pathways, or limb amputations. Their lifetime is of key importance; however, it is limited by the foreign body response of the tissue causing the loss of neurons and a reactive astrogliosis around the implant surface. Improving the biocompatibility of implant surfaces, especially promoting neuronal attachment and regeneration is therefore essential. In our work, bioactive properties of implanted black polySi nanostructured surfaces (520-800 nm long nanopillars with a diameter of 150-200 nm) were investigated and compared to microstructured Si surfaces in eight-week-long in vivo experiments. Glial encapsulation and local neuronal cell loss were characterised using GFAP and NeuN immunostaining respectively, followed by systematic image analysis. Regarding the severity of gliosis, no significant difference was observed in the vicinity of the different implant surfaces, however, the number of surviving neurons close to the nanostructured surface was higher than that of the microstructured ones. Our results imply that the functionality of implanted microelectrodes covered by Si nanopillars may lead to improved long-term recordings.

In vivo Characterization of Amorphous Silicon Carbide As a Biomaterial for Chronic Neural Interfaces.

PubMed

Knaack, Gretchen L; McHail, Daniel G; Borda, German; Koo, Beomseo; Peixoto, Nathalia; Cogan, Stuart F; Dumas, Theodore C; Pancrazio, Joseph J

2016-01-01

Implantable microelectrode arrays (MEAs) offer clinical promise for prosthetic devices by enabling restoration of communication and control of artificial limbs. While proof-of-concept recordings from MEAs have been promising, work in animal models demonstrates that the obtained signals degrade over time. Both material robustness and tissue response are acknowledged to have a role in device lifetime. Amorphous Silicon carbide (a-SiC), a robust material that is corrosion resistant, has emerged as an alternative encapsulation layer for implantable devices. We systematically examined the impact of a-SiC coating on Si probes by immunohistochemical characterization of key markers implicated in tissue-device response. After implantation, we performed device capture immunohistochemical labeling of neurons, astrocytes, and activated microglia/macrophages after 4 and 8 weeks of implantation. Neuron loss and microglia activation were similar between Si and a-SiC coated probes, while tissue implanted with a-SiC displayed a reduction in astrocytes adjacent to the probe. These results suggest that a-SiC has a similar biocompatibility profile as Si, and may be suitable for implantable MEA applications as a hermetic coating to prevent material degradation.

Chronic neural probe for simultaneous recording of single-unit, multi-unit, and local field potential activity from multiple brain sites

NASA Astrophysics Data System (ADS)

Pothof, F.; Bonini, L.; Lanzilotto, M.; Livi, A.; Fogassi, L.; Orban, G. A.; Paul, O.; Ruther, P.

2016-08-01

Objective. Drug resistant focal epilepsy can be treated by resecting the epileptic focus requiring a precise focus localisation using stereoelectroencephalography (SEEG) probes. As commercial SEEG probes offer only a limited spatial resolution, probes of higher channel count and design freedom enabling the incorporation of macro and microelectrodes would help increasing spatial resolution and thus open new perspectives for investigating mechanisms underlying focal epilepsy and its treatment. This work describes a new fabrication process for SEEG probes with materials and dimensions similar to clinical probes enabling recording single neuron activity at high spatial resolution. Approach. Polyimide is used as a biocompatible flexible substrate into which platinum electrodes and leads are integrated with a minimal feature size of 5 μm. The polyimide foils are rolled into the cylindrical probe shape at a diameter of 0.8 mm. The resulting probe features match those of clinically approved devices. Tests in saline solution confirmed the probe stability and functionality. Probes were implanted into the brain of one monkey (Macaca mulatta), trained to perform different motor tasks. Suitable configurations including up to 128 electrode sites allow the recording of task-related neuronal signals. Main results. Probes with 32 and 64 electrode sites were implanted in the posterior parietal cortex. Local field potentials and multi-unit activity were recorded as early as one hour after implantation. Stable single-unit activity was achieved for up to 26 days after implantation of a 64-channel probe. All recorded signals showed modulation during task execution. Significance. With the novel probes it is possible to record stable biologically relevant data over a time span exceeding the usual time needed for epileptic focus localisation in human patients. This is the first time that single units are recorded along cylindrical polyimide probes chronically implanted 22 mm deep into the brain of a monkey, which suggests the potential usefulness of this probe for human applications.

Chronic neural probe for simultaneous recording of single-unit, multi-unit, and local field potential activity from multiple brain sites.

PubMed

Pothof, F; Bonini, L; Lanzilotto, M; Livi, A; Fogassi, L; Orban, G A; Paul, O; Ruther, P

2016-08-01

Drug resistant focal epilepsy can be treated by resecting the epileptic focus requiring a precise focus localisation using stereoelectroencephalography (SEEG) probes. As commercial SEEG probes offer only a limited spatial resolution, probes of higher channel count and design freedom enabling the incorporation of macro and microelectrodes would help increasing spatial resolution and thus open new perspectives for investigating mechanisms underlying focal epilepsy and its treatment. This work describes a new fabrication process for SEEG probes with materials and dimensions similar to clinical probes enabling recording single neuron activity at high spatial resolution. Polyimide is used as a biocompatible flexible substrate into which platinum electrodes and leads are integrated with a minimal feature size of 5 μm. The polyimide foils are rolled into the cylindrical probe shape at a diameter of 0.8 mm. The resulting probe features match those of clinically approved devices. Tests in saline solution confirmed the probe stability and functionality. Probes were implanted into the brain of one monkey (Macaca mulatta), trained to perform different motor tasks. Suitable configurations including up to 128 electrode sites allow the recording of task-related neuronal signals. Probes with 32 and 64 electrode sites were implanted in the posterior parietal cortex. Local field potentials and multi-unit activity were recorded as early as one hour after implantation. Stable single-unit activity was achieved for up to 26 days after implantation of a 64-channel probe. All recorded signals showed modulation during task execution. With the novel probes it is possible to record stable biologically relevant data over a time span exceeding the usual time needed for epileptic focus localisation in human patients. This is the first time that single units are recorded along cylindrical polyimide probes chronically implanted 22 mm deep into the brain of a monkey, which suggests the potential usefulness of this probe for human applications.

In-Vivo Characterization of Glassy Carbon Micro-Electrode Arrays for Neural Applications and Histological Analysis of the Brain Tissue

NASA Astrophysics Data System (ADS)

Vomero, Maria

The aim of this work is to fabricate and characterize glassy carbon Microelectrode Arrays (MEAs) for sensing and stimulating neural activity, and conduct histological analysis of the brain tissue after the implant to determine long-term performance. Neural applications often require robust electrical and electrochemical response over a long period of time, and for those applications we propose to replace the commonly used noble metals like platinum, gold and iridium with glassy carbon. We submit that such material has the potential to improve the performances of traditional neural prostheses, thanks to better charge transfer capabilities and higher electrochemical stability. Great interest and attention is given in this work, in particular, to the investigation of tissue response after several weeks of implants in rodents' brain motor cortex and the associated materials degradation. As part of this work, a new set of devices for Electrocorticography (ECoG) has been designed and fabricated to improve durability and quality of the previous generation of devices, designed and manufactured by the same research group in 2014. In-vivo long-term impedance measurements and brain activity recordings were performed to test the functionality of the neural devices. In-vitro electrical characterization of the carbon electrodes, as well as the study of the adhesion mechanisms between glassy carbon and different substrates is also part of the research described in this book.

Flexible Chip Scale Package and Interconnect for Implantable MEMS Movable Microelectrodes for the Brain

PubMed Central

Jackson, Nathan; Muthuswamy, Jit

2009-01-01

We report here a novel approach called MEMS microflex interconnect (MMFI) technology for packaging a new generation of Bio-MEMS devices that involve movable microelectrodes implanted in brain tissue. MMFI addresses the need for (i) operating space for movable parts and (ii) flexible interconnects for mechanical isolation. We fabricated a thin polyimide substrate with embedded bond-pads, vias, and conducting traces for the interconnect with a backside dry etch, so that the flexible substrate can act as a thin-film cap for the MEMS package. A double gold stud bump rivet bonding mechanism was used to form electrical connections to the chip and also to provide a spacing of approximately 15–20 µm for the movable parts. The MMFI approach achieved a chip scale package (CSP) that is lightweight, biocompatible, having flexible interconnects, without an underfill. Reliability tests demonstrated minimal increases of 0.35 mΩ, 0.23 mΩ and 0.15 mΩ in mean contact resistances under high humidity, thermal cycling, and thermal shock conditions respectively. High temperature tests resulted in an increase in resistance of > 90 mΩ when aluminum bond pads were used, but an increase of ~ 4.2 mΩ with gold bond pads. The mean-time-to-failure (MTTF) was estimated to be at least one year under physiological conditions. We conclude that MMFI technology is a feasible and reliable approach for packaging and interconnecting Bio-MEMS devices. PMID:20160981

Effects of Intracortical Infusion of 6-Hydroxydopamine on the Response of Kitten Visual Cortex to Monocular Deprivation.

DTIC Science & Technology

1983-03-30

Research - Contract N00014-81-K-0136. 7.4 1% .4- b ,. Summary Between 4 and 10 weeks of age 10 normally reared kittens were bilaterally implanted with...projected with an ophthalmoscope and marked on a tangent screen at a distance of 114 cm. Single Unit Recording Tungsten-in-glass microelectrodes ( Levick ...quantitative measures of ocular dominance have been calculated. Binocularity ( B ), as defined by Pettigrew and Kasamatsu (1978). is the number of cells in ocular

Graphene-based carbon-layered electrode array technology for neural imaging and optogenetic applications

PubMed Central

Park, Dong-Wook; Schendel, Amelia A.; Mikael, Solomon; Brodnick, Sarah K.; Richner, Thomas J.; Ness, Jared P.; Hayat, Mohammed R.; Atry, Farid; Frye, Seth T.; Pashaie, Ramin; Thongpang, Sanitta; Ma, Zhenqiang; Williams, Justin C.

2014-01-01

Neural micro-electrode arrays that are transparent over a broad wavelength spectrum from ultraviolet to infrared could allow for simultaneous electrophysiology and optical imaging, as well as optogenetic modulation of the underlying brain tissue. The long-term biocompatibility and reliability of neural micro-electrodes also require their mechanical flexibility and compliance with soft tissues. Here we present a graphene-based, carbon-layered electrode array (CLEAR) device, which can be implanted on the brain surface in rodents for high-resolution neurophysiological recording. We characterize optical transparency of the device at >90% transmission over the ultraviolet to infrared spectrum and demonstrate its utility through optical interface experiments that use this broad spectrum transparency. These include optogenetic activation of focal cortical areas directly beneath electrodes, in vivo imaging of the cortical vasculature via fluorescence microscopy and 3D optical coherence tomography. This study demonstrates an array of interfacing abilities of the CLEAR device and its utility for neural applications. PMID:25327513

Ferrocene pixels by laser-induced forward transfer: towards flexible microelectrode printing

NASA Astrophysics Data System (ADS)

Mitu, B.; Matei, A.; Filipescu, M.; Palla Papavlu, A.; Bercea, A.; Lippert, T.; Dinescu, M.

2017-03-01

The aim of this work is to demonstrate the potential of laser-induced forward transfer (LIFT) as a printing technology, alternative to standard microfabrication techniques, in the area of flexible micro-electrode fabrication. First, ferrocene thin films are deposited onto fused silica and fused silica substrates previously coated with a photodegradable polymer film (triazene polymer) by matrix assisted pulsed laser evaporation (MAPLE). The morphology and chemical structure of the ferrocene thin films deposited by MAPLE has been investigated by atomic force microscopy and Fourier transformed infrared spectroscopy, and no structural damage occurs as a result of the laser deposition. Second, LIFT is applied to print for the first time ferrocene pixels and lines onto flexible polydimethylsiloxane (PDMS) substrates. The ferrocene pixels and lines are flawlessly transferred onto the PDMS substrates in air at room temperature, without the need of additional conventional photolithography processes. We believe that these results are very promising for a variety of applications ranging from flexible electronics to lab-on-a-chip devices, MEMS, and medical implants.

Multicontrast multiecho FLASH MRI for targeting the subthalamic nucleus.

PubMed

Xiao, Yiming; Beriault, Silvain; Pike, G Bruce; Collins, D Louis

2012-06-01

The subthalamic nucleus (STN) is one of the most common stimulation targets for treating Parkinson's disease using deep brain stimulation (DBS). This procedure requires precise placement of the stimulating electrode. Common practice of DBS implantation utilizes microelectrode recording to locate the sites with the correct electrical response after an initial location estimate based on a universal human brain atlas that is linearly scaled to the patient's anatomy as seen on the preoperative images. However, this often results in prolonged surgical time and possible surgical complications since the small-sized STN is difficult to visualize on conventional magnetic resonance (MR) images and its intersubject variability is not sufficiently considered in the atlas customization. This paper proposes a multicontrast, multiecho MR imaging (MRI) method that directly delineates the STN and other basal ganglia structures through five co-registered image contrasts (T1-weighted navigation image, R2 map, susceptibility-weighted imaging (phase, magnitude and fusion image)) obtained within a clinically acceptable time. The image protocol was optimized through both simulation and in vivo experiments to obtain the best image quality. Taking advantage of the multiple echoes and high readout bandwidths, no interimage registration is required since all images are produced in one acquisition, and image distortion and chemical shift are reduced. This MRI protocol is expected to mitigate some of the shortcomings of the state-of-the-art DBS implantation methods. Copyright © 2012 Elsevier Inc. All rights reserved.

Microstimulation with Chronically Implanted Intracortical Electrodes

NASA Astrophysics Data System (ADS)

McCreery, Douglas

Stimulating microelectrodes that penetrate into the brain afford a means of accessing the basic functional units of the central nervous system. Microstimulation in the region of the cerebral cortex that subserve vision may be an alternative, or an adjunct, to a retinal prosthesis, and may be particularly attractive as a means of restoring a semblance of high-resolution central vision. There also is the intriguing possibility that such a prosthesis could convey higher order visual percepts, many of which are mediated by neural circuits in the secondary or "extra-striate" visual areas that surround the primary visual cortex. The technologies of intracortical stimulating microelectrodes and investigations of the effects of microstimulation on neural tissue have advanced to the point where a cortical-level prosthesis is at least feasible. The imperative of protecting neural tissue from stimulation-induced damage imposes constraints on the selection of stimulus parameters, as does the requirement that the stimulation not greatly affect the electrical excitability of the neurons that are to be activated. The latter is especially likely to occur when many adjacent microelectrodes are pulsed, as will be necessary in a visual prosthesis. However, data from animal studies indicates that these restrictions on stimulus parameter are compatible with those that can evoke visual percepts in humans and in experimental animals. These findings give cause to be optimistic about the prospects for realizing a visual prosthesis utilizing intracortical microstimulation.

Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies

PubMed Central

Harris, J P; Capadona, J R; Miller, R H; Healy, B C; Shanmuganathan, K; Rowan, S J; Weder, C; Tyler, D J

2012-01-01

The hypothesis is that mechanical mismatch between brain tissue and microelectrodes influences the inflammatory response. Our unique, mechanically-adaptive polymer nanocomposite enabled this study within the cerebral cortex of rats. The initial tensile storage modulus of 5 GPa decreases to 12 MPa within 15 minutes under physiological conditions. The response to the nanocomposite was compared to surface-matched, stiffer implants of traditional wires (411 GPa) coated with the identical polymer substrate and implanted on the contralateral side. Both implants were tethered. Fluorescent immunohistochemistry labeling examined neurons, intermediate filaments, macrophages, microglia, and proteoglycans. We demonstrate, for the first time, a system that decouples the mechanical and surface chemistry components of the neural response. The neuronal nuclei density within 100 μm of the device at four weeks post implantation was greater for the compliant nanocomposite compared to the stiff wire. At eight weeks post implantation, the neuronal nuclei density around the nanocomposite was maintained, but the density around the wire recovered to match the nanocomposite. The glial scar response to the compliant nanocomposite was less vigorous than to the stiffer wire. The results suggest that mechanically associated factors such as proteoglycans and intermediate filaments are important modulators of the response of the compliant nanocomposite. PMID:22049097

Evaluation of poly(3,4-ethylenedioxythiophene)/carbon nanotube neural electrode coatings for stimulation in the dorsal root ganglion

PubMed Central

Kolarcik, Christi L.; Catt, Kasey; Rost, Erika; Albrecht, Ingrid N.; Bourbeau, Dennis; Du, Zhanhong; Kozai, Takashi D.Y.; Luo, Xiliang; Weber, Douglas J.; Cui, X. Tracy

2015-01-01

Objective The dorsal root ganglion (DRG) is an attractive target for implanting neural electrode arrays that restore sensory function or provide therapy via stimulation. However, penetrating microelectrodes designed for these applications are small and deliver low currents. For long-term performance of microstimulation devices, novel coating materials are needed in part to decrease impedance values at the electrode-tissue interface and to increase charge storage capacity. Approach Conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and multiwall carbon nanotubes (CNTs) were coated on the electrode surface and doped with the anti-inflammatory drug, dexamethasone. Electrode characteristics and the tissue reaction around neural electrodes as the result of stimulation, coating and drug release were characterized. Hematoxylin and eosin staining along with antibodies recognizing Iba1 (microglia/macrophages), NF200 (neuronal axons), NeuN (neurons), vimentin (fibroblasts), caspase-3 (cell death) and L1 (neural cell adhesion molecule) were used. Quantitative image analyses were performed using MATLAB. Main Results Our results indicate that coated microelectrodes have lower in vitro and in vivo impedance values. Significantly less neuronal death/damage was observed with coated electrodes as compared to non-coated controls. The inflammatory response with the PEDOT/CNT-coated electrodes was also reduced. Significance This study is the first to report on the utility of these coatings in stimulation applications. Our results indicate PEDOT/CNT coatings may be valuable additions to implantable electrodes used as therapeutic modalities. PMID:25485675

Evaluation of poly(3,4-ethylenedioxythiophene)/carbon nanotube neural electrode coatings for stimulation in the dorsal root ganglion

NASA Astrophysics Data System (ADS)

Kolarcik, Christi L.; Catt, Kasey; Rost, Erika; Albrecht, Ingrid N.; Bourbeau, Dennis; Du, Zhanhong; Kozai, Takashi D. Y.; Luo, Xiliang; Weber, Douglas J.; Cui, X. Tracy

2015-02-01

Objective. The dorsal root ganglion is an attractive target for implanting neural electrode arrays that restore sensory function or provide therapy via stimulation. However, penetrating microelectrodes designed for these applications are small and deliver low currents. For long-term performance of microstimulation devices, novel coating materials are needed in part to decrease impedance values at the electrode-tissue interface and to increase charge storage capacity. Approach. Conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and multi-wall carbon nanotubes (CNTs) were coated on the electrode surface and doped with the anti-inflammatory drug, dexamethasone. Electrode characteristics and the tissue reaction around neural electrodes as a result of stimulation, coating and drug release were characterized. Hematoxylin and eosin staining along with antibodies recognizing Iba1 (microglia/macrophages), NF200 (neuronal axons), NeuN (neurons), vimentin (fibroblasts), caspase-3 (cell death) and L1 (neural cell adhesion molecule) were used. Quantitative image analyses were performed using MATLAB. Main results. Our results indicate that coated microelectrodes have lower in vitro and in vivo impedance values. Significantly less neuronal death/damage was observed with coated electrodes as compared to non-coated controls. The inflammatory response with the PEDOT/CNT-coated electrodes was also reduced. Significance. This study is the first to report on the utility of these coatings in stimulation applications. Our results indicate PEDOT/CNT coatings may be valuable additions to implantable electrodes used as therapeutic modalities.

Flexible Chip Scale Package and Interconnect for Implantable MEMS Movable Microelectrodes for the Brain.

PubMed

Jackson, Nathan; Muthuswamy, Jit

2009-04-01

We report here a novel approach called MEMS microflex interconnect (MMFI) technology for packaging a new generation of Bio-MEMS devices that involve movable microelectrodes implanted in brain tissue. MMFI addresses the need for (i) operating space for movable parts and (ii) flexible interconnects for mechanical isolation. We fabricated a thin polyimide substrate with embedded bond-pads, vias, and conducting traces for the interconnect with a backside dry etch, so that the flexible substrate can act as a thin-film cap for the MEMS package. A double gold stud bump rivet bonding mechanism was used to form electrical connections to the chip and also to provide a spacing of approximately 15-20 µm for the movable parts. The MMFI approach achieved a chip scale package (CSP) that is lightweight, biocompatible, having flexible interconnects, without an underfill. Reliability tests demonstrated minimal increases of 0.35 mΩ, 0.23 mΩ and 0.15 mΩ in mean contact resistances under high humidity, thermal cycling, and thermal shock conditions respectively. High temperature tests resulted in an increase in resistance of > 90 mΩ when aluminum bond pads were used, but an increase of ~ 4.2 mΩ with gold bond pads. The mean-time-to-failure (MTTF) was estimated to be at least one year under physiological conditions. We conclude that MMFI technology is a feasible and reliable approach for packaging and interconnecting Bio-MEMS devices.

Conductive nanogel-interfaced neural microelectrode arrays with electrically controlled in-situ delivery of manganese ions enabling high-resolution MEMRI for synchronous neural tracing with deep brain stimulation.

PubMed

Huang, Wei-Chen; Lo, Yu-Chih; Chu, Chao-Yi; Lai, Hsin-Yi; Chen, You-Yin; Chen, San-Yuan

2017-04-01

Chronic brain stimulation has become a promising physical therapy with increased efficacy and efficiency in the treatment of neurodegenerative diseases. The application of deep brain electrical stimulation (DBS) combined with manganese-enhanced magnetic resonance imaging (MEMRI) provides an unbiased representation of the functional anatomy, which shows the communication between areas of the brain responding to the therapy. However, it is challenging for the current system to provide a real-time high-resolution image because the incorporated MnCl 2 solution through microinjection usually results in image blurring or toxicity due to the uncontrollable diffusion of Mn 2+ . In this study, we developed a new type of conductive nanogel-based neural interface composed of amphiphilic chitosan-modified poly(3,4 -ethylenedioxythiophene) (PMSDT) that can exhibit biomimic structural/mechanical properties and ionic/electrical conductivity comparable to that of Au. More importantly, the PMSDT enables metal-ligand bonding with Mn 2+ ions, so that the system can release Mn 2+ ions rather than MnCl 2 solution directly and precisely controlled by electrical stimulation (ES) to achieve real-time high-resolution MEMRI. With the integration of PMSDT nanogel-based coating in polyimide-based microelectrode arrays, the post-implantation DBS enables frequency-dependent MR imaging in vivo, as well as small focal imaging in response to channel site-specific stimulation on the implant. The MR imaging of the implanted brain treated with 5-min electrical stimulation showed a thalamocortical neuronal pathway after 36 h, confirming the effective activation of a downstream neuronal circuit following DBS. By eliminating the susceptibility to artifact and toxicity, this system, in combination with a MR-compatible implant and a bio-compliant neural interface, provides a harmless and synchronic functional anatomy for DBS. The study demonstrates a model of MEMRI-functionalized DBS based on functional neural interface engineering and controllable delivery technology, which can be utilized in more detailed exploration of the functional anatomy in the treatment of neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Carbon-Nanotube-Based Electrodes for Biomedical Applications

NASA Technical Reports Server (NTRS)

Li, Jun; Meyyappan, M.

2008-01-01

A nanotube array based on vertically aligned nanotubes or carbon nanofibers has been invented for use in localized electrical stimulation and recording of electrical responses in selected regions of an animal body, especially including the brain. There are numerous established, emerging, and potential applications for localized electrical stimulation and/or recording, including treatment of Parkinson s disease, Tourette s syndrome, and chronic pain, and research on electrochemical effects involved in neurotransmission. Carbon-nanotube-based electrodes offer potential advantages over metal macroelectrodes (having diameters of the order of a millimeter) and microelectrodes (having various diameters ranging down to tens of microns) heretofore used in such applications. These advantages include the following: a) Stimuli and responses could be localized at finer scales of spatial and temporal resolution, which is at subcellular level, with fewer disturbances to, and less interference from, adjacent regions. b) There would be less risk of hemorrhage on implantation because nano-electrode-based probe tips could be configured to be less traumatic. c) Being more biocompatible than are metal electrodes, carbon-nanotube-based electrodes and arrays would be more suitable for long-term or permanent implantation. d) Unlike macro- and microelectrodes, a nano-electrode could penetrate a cell membrane with minimal disruption. Thus, for example, a nanoelectrode could be used to generate an action potential inside a neuron or in proximity of an active neuron zone. Such stimulation may be much more effective than is extra- or intracellular stimulation via a macro- or microelectrode. e) The large surface area of an array at a micron-scale footprint of non-insulated nanoelectrodes coated with a suitable electrochemically active material containing redox ingredients would make it possible to obtain a pseudocapacitance large enough to dissipate a relatively large amount of electric charge, so that a large stimulation current could be applied at a micron-scale region without exhausting the redox ingredients. f) Carbon nanotube array is more compatible with the three-dimensional network of tissues. Particularly, a better electrical-neural interface can be formed. g) A carbon nanotube array inlaid in insulating materials with only the ends exposed is an extremely sensitive electro-analysis tool that can measure the local neurotransmitter signal at extremely high sensitivity and temporal resolution.

Platinum nanowire microelectrode arrays for neurostimulation applications: Fabrication, characterization, and in-vitro retinal cell stimulation

NASA Astrophysics Data System (ADS)

Whalen, John J., III

Implantable electrical neurostimulating devices are being developed for a number of applications, including artificial vision through retinal stimulation. The epiretinal prosthesis will use a two-dimensional array microelectrodes to address individual cells of the retina. MEMS fabrication processes can produce arrays of microelectrodes with these dimensions, but there are two critical issues that they cannot satisfy. One, the stimulating electrodes are the only part of the implanted electrical device that penetrate through the water impermeable package, and must do so without sacrificing hermeticity. Two, As electrode size decreases, the current density (A cm-2 ) increases, due to increased electrochemical impedance. This reduces the amount of charge that can be safely injected into the tissue. To date, MEMS processing method, cannot produce electrode arrays with good, prolonged hermetic properties. Similarly, MEMS approaches do not account for the increased impedance caused by decreased surface area. For these reasons there is a strong motivation for the development of a water-impermeable, substrate-penetrating electrode array with low electrochemical impedance. This thesis presents a stimulating electrode array fabricated from platinum nanowires using a modified electrochemical template synthesis approach. Nanowires are electrochemically deposited from ammonium hexachloroplatinate solution into lithographically patterned nanoporous anodic alumina templates to produce microarrays of platinum nanowires. The platinum nanowires penetrating through the ceramic aluminum oxide template serve as parallel electrical conduits through the water impermeable, electrically insulating substrate. Electrode impedance can be adjusted by either controlling the nanowire hydrous platinum oxide content or by partially etching the alumina template to expose additional surface area. A stepwise approach to this project was taken. First, the electrochemistry of ammonium hexachloroplatinate solution was characterized, and physical properties of electrodeposited thin films were correlated to deposition conditions used. Second, platinum nanowires were fabricated and their properties characterized, using similar deposition conditions. Third, the feasibility of fabricating platinum nanowire stimulating electrode arrays with a variety of surface structures was demonstrated. Fourth, the enhanced charge transfer characteristics of these structures were demonstrated using electrochemical techniques. Finally, retinal cell stimulation was demonstrated using electrodes from platinum nanowire arrays.

Novel platinum black electroplating technique improving mechanical stability.

PubMed

Kim, Raeyoung; Nam, Yoonkey

2013-01-01

Platinum black microelectrodes are widely used as an effective neural signal recording sensor. The simple fabrication process, high quality signal recording and proper biocompatibility are the main advantages of platinum black microelectrodes. When microelectrodes are exposed to actual biological system, various physical stimuli are applied. However, the porous structure of platinum black is vulnerable to external stimuli and destroyed easily. The impedance level of the microelectrode increases when the microelectrodes are damaged resulting in decreased recording performance. In this study, we developed mechanically stable platinum black microelectrodes by adding polydopamine. The polydopamine layer was added between the platinum black structures by electrodeposition method. The initial impedance level of platinum black only microelectrodes and polydopamine added microelectrodes were similar but after applying ultrasonication the impedance value dramatically increased for platinum black only microelectrodes, whereas polydopamine added microelectrodes showed little increase which were nearly retained initial values. Polydopamine added platinum black microelectrodes are expected to extend the availability as neural sensors.

An Implantable Neural Sensing Microsystem with Fiber-Optic Data Transmission and Power Delivery

PubMed Central

Park, Sunmee; Borton, David A.; Kang, Mingyu; Nurmikko, Arto V.; Song, Yoon-Kyu

2013-01-01

We have developed a prototype cortical neural sensing microsystem for brain implantable neuroengineering applications. Its key feature is that both the transmission of broadband, multichannel neural data and power required for the embedded microelectronics are provided by optical fiber access. The fiber-optic system is aimed at enabling neural recording from rodents and primates by converting cortical signals to a digital stream of infrared light pulses. In the full microsystem whose performance is summarized in this paper, an analog-to-digital converter and a low power digital controller IC have been integrated with a low threshold, semiconductor laser to extract the digitized neural signals optically from the implantable unit. The microsystem also acquires electrical power and synchronization clocks via optical fibers from an external laser by using a highly efficient photovoltaic cell on board. The implantable unit employs a flexible polymer substrate to integrate analog and digital microelectronics and on-chip optoelectronic components, while adapting to the anatomical and physiological constraints of the environment. A low power analog CMOS chip, which includes preamplifier and multiplexing circuitry, is directly flip-chip bonded to the microelectrode array to form the cortical neurosensor device. PMID:23666130

A Microelectrode Array with Reproducible Performance Shows Loss of Consistency Following Functionalization with a Self-Assembled 6-Mercapto-1-hexanol Layer.

PubMed

Corrigan, Damion K; Vezza, Vincent; Schulze, Holger; Bachmann, Till T; Mount, Andrew R; Walton, Anthony J; Terry, Jonathan G

2018-06-09

For analytical applications involving label-free biosensors and multiple measurements, i.e., across an electrode array, it is essential to develop complete sensor systems capable of functionalization and of producing highly consistent responses. To achieve this, a multi-microelectrode device bearing twenty-four equivalent 50 µm diameter Pt disc microelectrodes was designed in an integrated 3-electrode system configuration and then fabricated. Cyclic voltammetry and electrochemical impedance spectroscopy were used for initial electrochemical characterization of the individual working electrodes. These confirmed the expected consistency of performance with a high degree of measurement reproducibility for each microelectrode across the array. With the aim of assessing the potential for production of an enhanced multi-electrode sensor for biomedical use, the working electrodes were then functionalized with 6-mercapto-1-hexanol (MCH). This is a well-known and commonly employed surface modification process, which involves the same principles of thiol attachment chemistry and self-assembled monolayer (SAM) formation commonly employed in the functionalization of electrodes and the formation of biosensors. Following this SAM formation, the reproducibility of the observed electrochemical signal between electrodes was seen to decrease markedly, compromising the ability to achieve consistent analytical measurements from the sensor array following this relatively simple and well-established surface modification. To successfully and consistently functionalize the sensors, it was necessary to dilute the constituent molecules by a factor of ten thousand to support adequate SAM formation on microelectrodes. The use of this multi-electrode device therefore demonstrates in a high throughput manner irreproducibility in the SAM formation process at the higher concentration, even though these electrodes are apparently functionalized simultaneously in the same film formation environment, confirming that the often seen significant electrode-to-electrode variation in label-free SAM biosensing films formed under such conditions is not likely to be due to variation in film deposition conditions, but rather kinetically controlled variation in the SAM layer formation process at these microelectrodes.

The Argus(®) II Retinal Prosthesis System.

PubMed

Luo, Yvonne Hsu-Lin; da Cruz, Lyndon

2016-01-01

The Argus(®) II Retinal Prosthesis System (Second Sight Medical Products) is the first prosthetic vision device to obtain regulatory approval in both Europe and the USA. As such it has entered the commercial market as a treatment for patients with profound vision loss from end-stage outer retinal disease, predominantly retinitis pigmentosa. To date, over 100 devices have been implanted worldwide, representing the largest group of patients currently treated with visual prostheses. The system works by direct stimulation of the relatively preserved inner retina via epiretinal microelectrodes, thereby replacing the function of the degenerated photoreceptors. Visual information from a glasses-mounted video camera is converted to a pixelated image by an external processor, before being transmitted to the microelectrode array at the macula. Elicited retinal responses are then relayed via the normal optic nerve to the cortex for interpretation. We reviewed the animal and human studies that led to the development of the Argus(®) II device. A sufficiently robust safety profile was demonstrated in the phase I/II clinical trial of 30 patients. Improvement of function in terms of orientation and mobility, target localisation, shape and object recognition, and reading of letters and short unrehearsed words have also been shown. There remains a wide variability in the functional outcomes amongst the patients and the factors contributing to these performance differences are still unclear. Future developments in terms of both software and hardware aimed at improving visual function have been proposed. Further experience in clinical outcomes is being acquired due to increasing implantation. Copyright © 2015. Published by Elsevier Ltd.

On-chip enzymatic microbiofuel cell-powered integrated circuits.

PubMed

Mark, Andrew G; Suraniti, Emmanuel; Roche, Jérôme; Richter, Harald; Kuhn, Alexander; Mano, Nicolas; Fischer, Peer

2017-05-16

A variety of diagnostic and therapeutic medical technologies rely on long term implantation of an electronic device to monitor or regulate a patient's condition. One proposed approach to powering these devices is to use a biofuel cell to convert the chemical energy from blood nutrients into electrical current to supply the electronics. We present here an enzymatic microbiofuel cell whose electrodes are directly integrated into a digital electronic circuit. Glucose oxidizing and oxygen reducing enzymes are immobilized on microelectrodes of an application specific integrated circuit (ASIC) using redox hydrogels to produce an enzymatic biofuel cell, capable of harvesting electrical power from just a single droplet of 5 mM glucose solution. Optimisation of the fuel cell voltage and power to match the requirements of the electronics allow self-powered operation of the on-board digital circuitry. This study represents a step towards implantable self-powered electronic devices that gather their energy from physiological fluids.

Apparatus and method of inserting a microelectrode in body tissue or the like using vibration means

NASA Technical Reports Server (NTRS)

Feldstein, C.; Crawford, D. W.; Kanabus, E. W. (Inventor)

1979-01-01

An arrangement for and method of inserting a glass microelectrode having a tip in the micron range into body tissue is presented. The arrangement includes a microelectrode. The top of the microelectrode is attached to the diaphragm center of a first speaker. The microelectrode tip is brought into contact with the tissue by controlling a micromanipulator. Thereafter, an audio signal is applied to the speaker to cause the microelectrode to vibrate and thereby pierce the tissue surface without breaking the microelectrode tip. Thereafter, the tip is inserted into the tissue to the desired depth by operating the micromanipulator with the microelectrode in a vibratory or non-vibratory state.

Gamma oscillations precede interictal epileptiform spikes in the seizure onset zone

PubMed Central

Ren, Liankun; Kucewicz, Michal T.; Cimbalnik, Jan; Matsumoto, Joseph Y.; Brinkmann, Benjamin H.; Hu, Wei; Marsh, W. Richard; Meyer, Fredric B.; Stead, S. Matthew

2015-01-01

Objective: To investigate the generation, spectral characteristics, and potential clinical significance of brain activity preceding interictal epileptiform spike discharges (IEDs) recorded with intracranial EEG. Methods: Seventeen adult patients with drug-resistant temporal lobe epilepsy were implanted with intracranial electrodes as part of their evaluation for epilepsy surgery. IEDs detected on clinical macro- and research microelectrodes were analyzed using time-frequency spectral analysis. Results: Gamma frequency oscillations (30–100 Hz) often preceded IEDs in spatially confined brain areas. The gamma-IEDs were consistently observed 35 to 190 milliseconds before the epileptiform spike waveforms on individual macro- and microelectrodes. The gamma oscillations associated with IEDs had longer duration (p < 0.001) and slightly higher frequency (p = 0.045) when recorded on microelectrodes compared with clinical macroelectrodes. Although gamma-IEDs comprised only a subset of IEDs, they were strongly associated with electrodes in the seizure onset zone (SOZ) compared with the surrounding brain regions (p = 0.004), in sharp contrast to IEDs without preceding gamma oscillations that were often also detected outside of the SOZ. Similar to prior studies, isolated pathologic high-frequency oscillations in the gamma (30–100 Hz) and higher (100–600 Hz) frequency range, not associated with an IED, were also found to be associated with SOZ. Conclusions: The occurrence of locally generated gamma oscillations preceding IEDs suggests a mechanistic role for gamma in pathologic network activity generating IEDs. The results show a strong association between SOZ and gamma-IEDs. The potential clinical application of gamma-IEDs for mapping pathologic brain regions is intriguing, but will require future prospective studies. PMID:25589669

Optogenetically induced spatiotemporal gamma oscillations and neuronal spiking activity in primate motor cortex.

PubMed

Lu, Yao; Truccolo, Wilson; Wagner, Fabien B; Vargas-Irwin, Carlos E; Ozden, Ilker; Zimmermann, Jonas B; May, Travis; Agha, Naubahar S; Wang, Jing; Nurmikko, Arto V

2015-06-01

Transient gamma-band (40-80 Hz) spatiotemporal patterns are hypothesized to play important roles in cortical function. Here we report the direct observation of gamma oscillations as spatiotemporal waves induced by targeted optogenetic stimulation, recorded by intracortical multichannel extracellular techniques in macaque monkeys during their awake resting states. Microelectrode arrays integrating an optical fiber at their center were chronically implanted in primary motor (M1) and ventral premotor (PMv) cortices of two subjects. Targeted brain tissue was transduced with the red-shifted opsin C1V1(T/T). Constant (1-s square pulses) and ramp stimulation induced narrowband gamma oscillations during awake resting states. Recordings across 95 microelectrodes (4 × 4-mm array) enabled us to track the transient gamma spatiotemporal patterns manifested, e.g., as concentric expanding and spiral waves. Gamma oscillations were induced well beyond the light stimulation volume, via network interactions at distal electrode sites, depending on optical power. Despite stimulation-related modulation in spiking rates, neuronal spiking remained highly asynchronous during induced gamma oscillations. In one subject we examined stimulation effects during preparation and execution of a motor task and observed that movement execution largely attenuated optically induced gamma oscillations. Our findings demonstrate that, beyond previously reported induced gamma activity under periodic drive, a prolonged constant stimulus above a certain threshold may carry primate motor cortex network dynamics into gamma oscillations, likely via a Hopf bifurcation. More broadly, the experimental capability in combining microelectrode array recordings and optogenetic stimulation provides an important approach for probing spatiotemporal dynamics in primate cortical networks during various physiological and behavioral conditions.

Optogenetically induced spatiotemporal gamma oscillations and neuronal spiking activity in primate motor cortex

PubMed Central

Lu, Yao; Truccolo, Wilson; Wagner, Fabien B.; Vargas-Irwin, Carlos E.; Ozden, Ilker; Zimmermann, Jonas B.; May, Travis; Agha, Naubahar S.; Wang, Jing

2015-01-01

Transient gamma-band (40–80 Hz) spatiotemporal patterns are hypothesized to play important roles in cortical function. Here we report the direct observation of gamma oscillations as spatiotemporal waves induced by targeted optogenetic stimulation, recorded by intracortical multichannel extracellular techniques in macaque monkeys during their awake resting states. Microelectrode arrays integrating an optical fiber at their center were chronically implanted in primary motor (M1) and ventral premotor (PMv) cortices of two subjects. Targeted brain tissue was transduced with the red-shifted opsin C1V1(T/T). Constant (1-s square pulses) and ramp stimulation induced narrowband gamma oscillations during awake resting states. Recordings across 95 microelectrodes (4 × 4-mm array) enabled us to track the transient gamma spatiotemporal patterns manifested, e.g., as concentric expanding and spiral waves. Gamma oscillations were induced well beyond the light stimulation volume, via network interactions at distal electrode sites, depending on optical power. Despite stimulation-related modulation in spiking rates, neuronal spiking remained highly asynchronous during induced gamma oscillations. In one subject we examined stimulation effects during preparation and execution of a motor task and observed that movement execution largely attenuated optically induced gamma oscillations. Our findings demonstrate that, beyond previously reported induced gamma activity under periodic drive, a prolonged constant stimulus above a certain threshold may carry primate motor cortex network dynamics into gamma oscillations, likely via a Hopf bifurcation. More broadly, the experimental capability in combining microelectrode array recordings and optogenetic stimulation provides an important approach for probing spatiotemporal dynamics in primate cortical networks during various physiological and behavioral conditions. PMID:25761956

MEMS-based system and image processing strategy for epiretinal prosthesis.

PubMed

Xia, Peng; Hu, Jie; Qi, Jin; Gu, Chaochen; Peng, Yinghong

2015-01-01

Retinal prostheses have the potential to restore some level of visual function to the patients suffering from retinal degeneration. In this paper, an epiretinal approach with active stimulation devices is presented. The MEMS-based processing system consists of an external micro-camera, an information processor, an implanted electrical stimulator and a microelectrode array. The image processing strategy combining image clustering and enhancement techniques was proposed and evaluated by psychophysical experiments. The results indicated that the image processing strategy improved the visual performance compared with direct merging pixels to low resolution. The image processing methods assist epiretinal prosthesis for vision restoration.

Restoration of orbicularis oculi muscle function in rabbits with peripheral facial paralysis via an implantable artificial facial nerve system

PubMed Central

Sun, Yajing; Jin, Cheng; Li, Keyong; Zhang, Qunfeng; Geng, Liang; Liu, Xundao; Zhang, Yi

2017-01-01

The purpose of the present study was to restore orbicularis oculi muscle function using the implantable artificial facial nerve system (IAFNS). The in vivo part of the IAFNS was implanted into 12 rabbits that were facially paralyzed on the right side of the face to restore the function of the orbicularis oculi muscle, which was indicated by closure of the paralyzed eye when the contralateral side was closed. Wireless communication links were established between the in vivo part (the processing chip and microelectrode) and the external part (System Controller program) of the system, which were used to set the working parameters and indicate the working state of the processing chip and microelectrode implanted in the body. A disturbance field strength test of the IAFNS processing chip was performed in a magnetic field dark room to test its electromagnetic radiation safety. Test distances investigated were 0, 1, 3 and 10 m, and levels of radiation intensity were evaluated in the horizontal and vertical planes. Anti-interference experiments were performed to test the stability of the processing chip under the interference of electromagnetic radiation. The fully implanted IAFNS was run for 5 h per day for 30 consecutive days to evaluate the accuracy and precision as well as the long-term stability and effectiveness of wireless communication. The stimulus intensity (range, 0–8 mA) was set every 3 days to confirm the minimum stimulation intensity which could indicate the movement of the paralyzed side was set. Effective stimulation rate was also tested by comparing the number of eye-close movements on both sides. The results of the present study indicated that the IAFNS could rebuild the reflex arc, inducing the experimental rabbits to close the eye of the paralyzed side. The System Controller program was able to reflect the in vivo part of the artificial facial nerve system in real-time and adjust the working pattern, stimulation intensity and frequency, range of wave and stimulation time. No significant differences in the stimulus intensities were observed during 30 days. The artificial facial nerve system chip operation stable in the anti-interference test, and the radiation field strength of the system was in a safe range according to the national standard. The IAFNS functioned without any interference and was able to restore functionality to facially paralyzed rabbits over the course of 30 days. PMID:29285055

A regenerative microchannel device for recording multiple single-unit action potentials in awake, ambulatory animals.

PubMed

Srinivasan, Akhil; Tipton, John; Tahilramani, Mayank; Kharbouch, Adel; Gaupp, Eric; Song, Chao; Venkataraman, Poornima; Falcone, Jessica; Lacour, Stéphanie P; Stanley, Garrett B; English, Arthur W; Bellamkonda, Ravi V

2016-02-01

Despite significant advances in robotics, commercially advanced prosthetics provide only a small fraction of the functionality of the amputated limb that they are meant to replace. Peripheral nerve interfacing could provide a rich controlling link between the body and these advanced prosthetics in order to increase their overall utility. Here, we report on the development of a fully integrated regenerative microchannel interface with 30 microelectrodes and signal extraction capabilities enabling evaluation in an awake and ambulatory rat animal model. In vitro functional testing validated the capability of the microelectrodes to record neural signals similar in size and nature to those that occur in vivo. In vitro dorsal root ganglia cultures revealed striking cytocompatibility of the microchannel interface. Finally, in vivo, the microchannel interface was successfully used to record a multitude of single-unit action potentials through 63% of the integrated microelectrodes at the early time point of 3 weeks. This marks a significant advance in microchannel interfacing, demonstrating the capability of microchannels to be used for peripheral nerve interfacing. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Microfabricated FSCV-Compatible Microelectrode Array for Real-time Monitoring of Heterogeneous Dopamine Release

PubMed Central

Zachek, Matthew K.; Park, Jinwoo; Takmakov, Pavel; Wightman, R. Mark; McCarty, Gregory S.

2010-01-01

Fast scan cyclic voltammetry (FSCV) has been used previously to detect neurotransmitter release and reuptake in vivo. An advantage that FSCV has over other electrochemical techniques is its ability to distinguish neurotransmitters of interest (i.e. monoamines) from their metabolites using their respective characteristic cyclic voltammogram. While much has been learned with this technique, it has generally only been used in a single working electrode arrangement. Additionally, traditional electrode fabrication techniques tend to be difficult and somewhat irreproducible. Described in this report is a fabrication method for a FSCV compatible microelectrode array (FSCV-MEA) that is capable of functioning in vivo. The microfabrication techniques employed here allow for better reproducibility than traditional fabrication methods of carbon fiber microelectrodes, and enable batch fabrication of electrode arrays. The reproducibility and electrochemical qualities of the probes were assessed along with cross talk in vitro. Heterogeneous release of electrically stimulated dopamine was observed in real-time in the striatum of an anesthetized rat using the FSCV-MEA. The heterogeneous effects of pharmacology on the striatum was also observed and shown to be consistent across multiple animals. PMID:20464031

Combination of High-density Microelectrode Array and Patch Clamp Recordings to Enable Studies of Multisynaptic Integration.

PubMed

Jäckel, David; Bakkum, Douglas J; Russell, Thomas L; Müller, Jan; Radivojevic, Milos; Frey, Urs; Franke, Felix; Hierlemann, Andreas

2017-04-20

We present a novel, all-electric approach to record and to precisely control the activity of tens of individual presynaptic neurons. The method allows for parallel mapping of the efficacy of multiple synapses and of the resulting dynamics of postsynaptic neurons in a cortical culture. For the measurements, we combine an extracellular high-density microelectrode array, featuring 11'000 electrodes for extracellular recording and stimulation, with intracellular patch-clamp recording. We are able to identify the contributions of individual presynaptic neurons - including inhibitory and excitatory synaptic inputs - to postsynaptic potentials, which enables us to study dendritic integration. Since the electrical stimuli can be controlled at microsecond resolution, our method enables to evoke action potentials at tens of presynaptic cells in precisely orchestrated sequences of high reliability and minimum jitter. We demonstrate the potential of this method by evoking short- and long-term synaptic plasticity through manipulation of multiple synaptic inputs to a specific neuron.

Asleep Deep Brain Stimulation Reduces Incidence of Intracranial Air during Electrode Implantation.

PubMed

Ko, Andrew L; Magown, Philippe; Ozpinar, Alp; Hamzaoglu, Vural; Burchiel, Kim J

2018-05-30

Asleep deep brain stimulation (aDBS) implantation replaces microelectrode recording for image-guided implantation, shortening the operative time and reducing cerebrospinal fluid egress. This may decrease pneumocephalus, thus decreasing brain shift during implantation. To compare the incidence and volume of pneumocephalus during awake (wkDBS) and aDBS procedures. A retrospective review of bilateral DBS cases performed at Oregon Health & Science University from 2009 to 2017 was undertaken. Postimplantation imaging was reviewed to determine the presence and volume of intracranial air and measure cortical brain shift. Among 371 patients, pneumocephalus was noted in 66% of wkDBS and 15.6% of aDBS. The average volume of air was significantly higher in wkDBS than aDBS (8.0 vs. 1.8 mL). Volumes of air greater than 7 mL, which have previously been linked to brain shift, occurred significantly more frequently in wkDBS than aDBS (34 vs 5.6%). wkDBS resulted in significantly larger cortical brain shifts (5.8 vs. 1.2 mm). We show that aDBS reduces the incidence of intracranial air, larger air volumes, and cortical brain shift. Large volumes of intracranial air have been correlated to shifting of brain structures during DBS procedures, a variable that could impact accuracy of electrode placement. © 2018 S. Karger AG, Basel.

COMMUNICATION: Minocycline increases quality and longevity of chronic neural recordings

NASA Astrophysics Data System (ADS)

Rennaker, R. L.; Miller, J.; Tang, H.; Wilson, D. A.

2007-06-01

Brain/machine interfaces could potentially be used in the treatment of a host of neurological disorders ranging from paralysis to sensory deficits. Insertion of chronic micro-electrode arrays into neural tissue initiates a host of immunological responses, which typically leads to the formation of a cellular sheath around the implant, resulting in the loss of useful signals. Minocycline has been shown to have neuroprotective and neurorestorative effects in certain neural injury and neurodegenerative disease models. This study examined the effects of minocycline administration on the quality and longevity of chronic multi-channel microwire neural implants 1 week and 1 month post-implantation in auditory cortex. The mean signal-to-noise ratio for the minocycline group stabilized at the end of week 1 and remained above 4.6 throughout the following 3 weeks. The control group signal-to-noise ratio dropped throughout the duration of the study and at the end of 4 weeks was 2.6. Furthermore, 68% of electrodes from the minocycline group showed significant stimulus-driven activity at week 4 compared to 12.5% of electrodes in the control group. There was a significant reduction in the number of activated astrocytes around the implant in minocycline subjects, as well as a reduction in total area occupied by activated astrocytes at 1 and 4 weeks.

Microelectrode Array-evaluation of Neurotoxic Effects of Magnesium as an Implantable Biomaterial

PubMed Central

Huang, Ting; Wang, Zhonghai; Wei, Lina; Kindy, Mark; Zheng, Yufeng; Xi, Tingfei; Gao, Bruce Z.

2016-01-01

Magnesium (Mg)-based biomaterials have shown great potential in clinical applications. However, the cytotoxic effects of excessive Mg2+ and the corrosion products from Mg-based biomaterials, particularly their effects on neurons, have been little studied. Although viability tests are most commonly used, a functional evaluation is critically needed. Here, both methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays were used to test the effect of Mg2+ and Mg-extract solution on neuronal viability. Microelectrode arrays (MEAs), which provide long-term, real-time recording of extracellular electrophysiological signals of in vitro neuronal networks, were used to test for toxic effects. The minimum effective concentrations (ECmin) of Mg2+ from the MTT and LDH assays were 3 mmol/L and 100 mmol/L, respectively, while the ECmin obtained from the MEA assay was 0.1 mmol/L. MEA data revealed significant loss of neuronal network activity when the culture was exposed to 25% Mg-extract solution, a concentration that did not affect neuronal viability. For evaluating the biocompatibility of Mg-based biomaterials with neurons, MEA electrophysiological testing is a more precise method than basic cell-viability testing. PMID:27110081

Microelectrode Array-evaluation of Neurotoxic Effects of Magnesium as an Implantable Biomaterial.

PubMed

Huang, Ting; Wang, Zhonghai; Wei, Lina; Kindy, Mark; Zheng, Yufeng; Xi, Tingfei; Gao, Bruce Z

2016-01-01

Magnesium (Mg)-based biomaterials have shown great potential in clinical applications. However, the cytotoxic effects of excessive Mg 2+ and the corrosion products from Mg-based biomaterials, particularly their effects on neurons, have been little studied. Although viability tests are most commonly used, a functional evaluation is critically needed. Here, both methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays were used to test the effect of Mg 2+ and Mg-extract solution on neuronal viability. Microelectrode arrays (MEAs), which provide long-term, real-time recording of extracellular electrophysiological signals of in vitro neuronal networks, were used to test for toxic effects. The minimum effective concentrations (EC min ) of Mg 2+ from the MTT and LDH assays were 3 mmol/L and 100 mmol/L, respectively, while the EC min obtained from the MEA assay was 0.1 mmol/L. MEA data revealed significant loss of neuronal network activity when the culture was exposed to 25% Mg-extract solution, a concentration that did not affect neuronal viability. For evaluating the biocompatibility of Mg-based biomaterials with neurons, MEA electrophysiological testing is a more precise method than basic cell-viability testing.

Flexible Neural Electrode Array Based-on Porous Graphene for Cortical Microstimulation and Sensing

NASA Astrophysics Data System (ADS)

Lu, Yichen; Lyu, Hongming; Richardson, Andrew G.; Lucas, Timothy H.; Kuzum, Duygu

2016-09-01

Neural sensing and stimulation have been the backbone of neuroscience research, brain-machine interfaces and clinical neuromodulation therapies for decades. To-date, most of the neural stimulation systems have relied on sharp metal microelectrodes with poor electrochemical properties that induce extensive damage to the tissue and significantly degrade the long-term stability of implantable systems. Here, we demonstrate a flexible cortical microelectrode array based on porous graphene, which is capable of efficient electrophysiological sensing and stimulation from the brain surface, without penetrating into the tissue. Porous graphene electrodes show superior impedance and charge injection characteristics making them ideal for high efficiency cortical sensing and stimulation. They exhibit no physical delamination or degradation even after 1 million biphasic stimulation cycles, confirming high endurance. In in vivo experiments with rodents, same array is used to sense brain activity patterns with high spatio-temporal resolution and to control leg muscles with high-precision electrical stimulation from the cortical surface. Flexible porous graphene array offers a minimally invasive but high efficiency neuromodulation scheme with potential applications in cortical mapping, brain-computer interfaces, treatment of neurological disorders, where high resolution and simultaneous recording and stimulation of neural activity are crucial.

Fabrication and mechanical characterization of long and different penetrating length neural microelectrode arrays

NASA Astrophysics Data System (ADS)

Goncalves, S. B.; Peixoto, A. C.; Silva, A. F.; Correia, J. H.

2015-05-01

This paper presents a detailed description of the design, fabrication and mechanical characterization of 3D microelectrode arrays (MEA) that comprise high aspect-ratio shafts and different penetrating lengths of electrodes (from 3 mm to 4 mm). The array’s design relies only on a bulk silicon substrate dicing saw technology. The encapsulation process is accomplished by a medical epoxy resin and platinum is used as the transduction layer between the probe and neural tissue. The probe’s mechanical behaviour can significantly affect the neural tissue during implantation time. Thus, we measured the MEA maximum insertion force in an agar gel phantom and a porcine cadaver brain. Successful 3D MEA were produced with shafts of 3 mm, 3.5 mm and 4 mm in length. At a speed of 180 mm min-1, the MEA show maximum penetrating forces per electrode of 2.65 mN and 12.5 mN for agar and brain tissue, respectively. A simple and reproducible fabrication method was demonstrated, capable of producing longer penetrating shafts than previously reported arrays using the same fabrication technology. Furthermore, shafts with sharp tips were achieved in the fabrication process simply by using a V-shaped blade.

Applying a foil queue micro-electrode in micro-EDM to fabricate a 3D micro-structure

NASA Astrophysics Data System (ADS)

Xu, Bin; Guo, Kang; Wu, Xiao-yu; Lei, Jian-guo; Liang, Xiong; Guo, Deng-ji; Ma, Jiang; Cheng, Rong

2018-05-01

Applying a 3D micro-electrode in a micro electrical discharge machining (micro-EDM) can fabricate a 3D micro-structure with an up and down reciprocating method. However, this processing method has some shortcomings, such as a low success rate and a complex process for fabrication of 3D micro-electrodes. By focusing on these shortcomings, this paper proposed a novel 3D micro-EDM process based on the foil queue micro-electrode. Firstly, a 3D micro-electrode was discretized into several foil micro-electrodes and these foil micro-electrodes constituted a foil queue micro-electrode. Then, based on the planned process path, foil micro-electrodes were applied in micro-EDM sequentially and the micro-EDM results of each foil micro-electrode were able to superimpose the 3D micro-structure. However, the step effect will occur on the 3D micro-structure surface, which has an adverse effect on the 3D micro-structure. To tackle this problem, this paper proposes to reduce this adverse effect by rounded corner wear at the end of the foil micro-electrode and studies the impact of machining parameters on rounded corner wear and the step effect on the micro-structure surface. Finally, using a wire cutting voltage of 80 V, a current of 0.5 A and a pulse width modulation ratio of 1:4, the foil queue micro-electrode was fabricated by wire electrical discharge machining. Also, using a pulse width of 100 ns, a pulse interval of 200 ns, a voltage of 100 V and workpiece material of 304# stainless steel, the foil queue micro-electrode was applied in micro-EDM for processing of a 3D micro-structure with hemispherical features, which verified the feasibility of this process.

Electrostatic Microactuators for Precise Positioning of Neural Microelectrodes

PubMed Central

Muthuswamy, Jit; Okandan, Murat; Jain, Tilak; Gilletti, Aaron

2006-01-01

Microelectrode arrays used for monitoring single and multineuronal action potentials often fail to record from the same population of neurons over a period of time likely due to micromotion of neurons away from the microelectrode, gliosis around the recording site and also brain movement due to behavior. We report here novel electrostatic microactuated microelectrodes that will enable precise repositioning of the microelectrodes within the brain tissue. Electrostatic comb-drive microactuators and associated microelectrodes are fabricated using the SUMMiT V™ (Sandia's Ultraplanar Multilevel MEMS Technology) process, a five-layer polysilicon micromachining technology of the Sandia National labs, NM. The microfabricated microactuators enable precise bidirectional positioning of the microelectrodes in the brain with accuracy in the order of 1 μm. The microactuators allow for a linear translation of the microelectrodes of up to 5 mm in either direction making it suitable for positioning microelectrodes in deep structures of a rodent brain. The overall translation was reduced to approximately 2 mm after insulation of the microelectrodes with epoxy for monitoring multiunit activity. The microactuators are capable of driving the microelectrodes in the brain tissue with forces in the order of several micro-Newtons. Single unit recordings were obtained from the somatosensory cortex of adult rats in acute experiments demonstrating the feasibility of this technology. Further optimization of the insulation, packaging and interconnect issues will be necessary before this technology can be validated in long-term experiments. PMID:16235660

Potential for thermal damage to the blood–brain barrier during craniotomy: implications for intracortical recording microelectrodes

NASA Astrophysics Data System (ADS)

Shoffstall, Andrew J.; Paiz, Jen E.; Miller, David M.; Rial, Griffin M.; Willis, Mitchell T.; Menendez, Dhariyat M.; Hostler, Stephen R.; Capadona, Jeffrey R.

2018-06-01

Objective. Our objective was to determine how readily disruption of the blood–brain barrier (BBB) occurred as a result of bone drilling during a craniotomy to implant microelectrodes in rat cortex. While the phenomenon of heat production during bone drilling is well known, practices to evade damage to the underlying brain tissue are inconsistently practiced and reported in the literature. Approach. We conducted a review of the intracortical microelectrode literature to summarize typical approaches to mitigate drill heating during rodent craniotomies. Post mortem skull-surface and transient brain-surface temperatures were experimentally recorded using an infrared camera and thermocouple, respectively. A number of drilling conditions were tested, including varying drill speed and continuous versus intermittent contact. In vivo BBB permeability was assayed 1 h after the craniotomy procedure using Evans blue dye. Main results. Of the reviewed papers that mentioned methods to mitigate thermal damage during craniotomy, saline irrigation was the most frequently cited (in six of seven papers). In post mortem tissues, we observed increases in skull-surface temperature ranging from  +3 °C to  +21 °C, dependent on drill speed. In vivo, pulsed-drilling (2 s-on/2 s-off) and slow-drilling speeds (1000 r.p.m.) were the most effective methods we studied to mitigate heating effects from drilling, while inconclusive results were obtained with saline irrigation. Significance. Neuroinflammation, initiated by damage to the BBB and perpetuated by the foreign body response, is thought to play a key role in premature failure of intracortical recording microelectrodes. This study demonstrates the extreme sensitivity of the BBB to overheating caused by bone drilling. To avoid damage to the BBB, the authors recommend that craniotomies be drilled with slow speeds and/or with intermittent drilling with complete removal of the drill from the skull during ‘off’ periods. While saline alone was ineffective at preventing overheating, its use is still recommended to remove bone dust from the surgical site and to augment other cooling methods.

Characterizing the Material Properties of Polymer-Based Microelectrode Arrays for Retinal Prosthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Christina Soyeun

2003-06-01

The Retinal Prosthesis project is a three year project conducted in part at the Lawrence Livermore National Laboratory and funded by the Department of Energy to create an epiretinal microelectrode array for stimulating retinal cells. The implant must be flexible to conform to the retina, robust to sustain handling during fabrication and implantation, and biocompatible to withstand physiological conditions within the eye. Using poly(dimethyl siloxane) (PDMS), LLNL aims to use microfabrication techniques to increase the number of electrodes and integrate electronics. After the initial designs were fabricated and tested in acute implantation, it became obvious that there was a needmore » to characterize and understand the mechanical and electrical properties of these new structures. This knowledge would be imperative in gaining credibility for polymer microfabrication and optimizing the designs. Thin composite microfabricated devices are challenging to characterize because they are difficult to handle, and exhibit non-linear, viscoelastic, and anisotropic properties. The objective of this research is to device experiments and protocols, develop an analytical model to represent the composite behavior, design and fabricate test structures, and conduct experimental testing to determine the mechanical and electrical properties of PDMS-metal composites. Previous uniaxial stretch tests show an average of 7% strain before failure on resistive heaters of similar dimensions deposited on PDMS. Lack of background information and questionable human accuracy demands a more sophisticated and thorough testing method. An Instron tensile testing machine was set up to interface with a digital multiplexor and computer interface to simultaneously record and graph position, load, and resistance across devices. With a compliant load cell for testing polymers and electrical interconnect grips designed and fabricated to interface the sample to the electronics, real-time resistance measurements were taken. Wafers of test structures were fabricated with variables such as lead width, pad to lead interface shape, PDMS thickness, metal (Ti and Au) thickness, and lead shape. Results showed that the serpentine shaped leads were 70% more effective, and that thicker adhesion layers of Ti were too brittle for testing. The other variables did not produce significant results.« less

A tapered aluminium microelectrode array for improvement of dielectrophoresis-based particle manipulation.

PubMed

Buyong, Muhamad Ramdzan; Larki, Farhad; Faiz, Mohd Syafiq; Hamzah, Azrul Azlan; Yunas, Jumrail; Majlis, Burhanuddin Yeop

2015-05-11

In this work, the dielectrophoretic force (F(DEP)) response of Aluminium Microelectrode Arrays with tapered profile is investigated through experimental measurements and numerical simulations. A standard CMOS processing technique with a step for the formation of a tapered profile resist is implemented in the fabrication of Tapered Aluminium Microelectrode Arrays (TAMA). The F(DEP) is investigated through analysis of the Clausius-Mossotti factor (CMF) and cross-over frequency (f(xo)). The performance of TAMA with various side wall angles is compared to that of microelectrodes with a straight cut sidewall profile over a wide range of frequencies through FEM numerical simulations. Additionally, electric field measurement (EFM) is performed through scanning probe microscopy (SPM) in order to obtain the region of force focus in both platforms. Results showed that the tapered profile microelectrodes with angles between 60° and 70° produce the highest electric field gradient on the particles. Also, the region of the strongest electric field in TAMA is located at the bottom and top edge of microelectrode while the strongest electric field in microelectrodes with straight cut profile is found at the top corner of the microelectrode. The latter property of microelectrodes improves the probability of capturing/repelling the particles at the microelectrode's side wall.

Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies

PubMed Central

2015-01-01

Implantable biosensors are valuable scientific tools for basic neuroscience research and clinical applications. Neurotechnologies provide direct readouts of neurological signal and neurochemical processes. These tools are generally most valuable when performance capacities extend over months and years to facilitate the study of memory, plasticity, and behavior or to monitor patients’ conditions. These needs have generated a variety of device designs from microelectrodes for fast scan cyclic voltammetry (FSCV) and electrophysiology to microdialysis probes for sampling and detecting various neurochemicals. Regardless of the technology used, the breaching of the blood–brain barrier (BBB) to insert devices triggers a cascade of biochemical pathways resulting in complex molecular and cellular responses to implanted devices. Molecular and cellular changes in the microenvironment surrounding an implant include the introduction of mechanical strain, activation of glial cells, loss of perfusion, secondary metabolic injury, and neuronal degeneration. Changes to the tissue microenvironment surrounding the device can dramatically impact electrochemical and electrophysiological signal sensitivity and stability over time. This review summarizes the magnitude, variability, and time course of the dynamic molecular and cellular level neural tissue responses induced by state-of-the-art implantable devices. Studies show that insertion injuries and foreign body response can impact signal quality across all implanted central nervous system (CNS) sensors to varying degrees over both acute (seconds to minutes) and chronic periods (weeks to months). Understanding the underlying biological processes behind the brain tissue response to the devices at the cellular and molecular level leads to a variety of intervention strategies for improving signal sensitivity and longevity. PMID:25546652

Micromachined devices for interfacing neurons

NASA Astrophysics Data System (ADS)

Stieglitz, Thomas; Beutel, Hansjoerg; Blau, Cornelia; Meyer, Joerg-Uwe

1998-07-01

Micromachining technologies were established to fabricate microelectrode arrays and devices for interfacing parts of the central or peripheral nervous system. The devices were part of a neural prosthesis that allows simultaneous multichannel recording and multisite stimulation of neurons. Overcoming the brittle mechanics of silicon devices and challenging housing demands close to the nerve we established a process technology to fabricate light-weighted and highly flexible polyimide based devices. Platinum and iridium thin-film electrodes were embedded in the polyimide. With reactive ion etching we got the possibility to simply integrate interconnections and to form nearly arbitrary outer shapes of the devices. We designed multichannel devices with up to 24 electrodes in the shape of plates, hooks and cuffs for different applications. In vitro tests exhibited stable electrode properties and no cytotoxicity of the materials and the devices. Sieve electrodes were chronically implanted in rats to interface the regenerating sciatic nerve. After six months, recordings and stimulation of the nerve via electrodes on the micro-device proved functional reinnervation of the limb. Concentric circular structures were designed for a retina implant for the blind. In preliminary studies in rabbits, evoked potentials in the visual cortex corresponded to stimulation sites of the implant.

Methods for implantation of micro-wire bundles and optimization of single/multiunit recordings from human mesial temporal lobe

PubMed Central

Misra, A; Burke, JF; Ramayya, A; Jacobs, J; Sperling, MR; Moxon, KA; Kahana, MJ; Evans, JJ; Sharan, AD

2014-01-01

Objective The authors report methods developed for the implantation of micro-wire bundles into mesial temporal lobe structures and subsequent single neuron recording in epileptic patients undergoing in-patient diagnostic monitoring. This is done with the intention of lowering the perceived barriers to routine single neuron recording from deep brain structures in the clinical setting. Approach Over a 15 month period, 11 patients were implanted with platinum micro-wire bundles into mesial temporal structures. Protocols were developed for A) monitoring electrode integrity through impedance testing, B) ensuring continuous 24-7 recording, C) localizing micro-wire position and “splay” pattern and D) monitoring grounding and referencing to maintain the quality of recordings. Main Result Five common modes of failure were identified: 1) broken micro-wires from acute tensile force, 2) broken micro-wires from cyclic fatigue at stress points, 3) poor in-vivo micro-electrode separation, 4) motion artifact and 5) deteriorating ground connection and subsequent drop in common mode noise rejection. Single neurons have been observed up to 14 days post implantation and on 40% of micro-wires. Significance Long-term success requires detailed review of each implant by both the clinical and research teams to identify failure modes, and appropriate refinement of techniques while moving forward. This approach leads to reliable unit recordings without prolonging operative times, which will help increase the availability and clinical viability of human single neuron data. PMID:24608589

In vivo monitoring of glial scar proliferation on chronically implanted neural electrodes by fiber optical coherence tomography

PubMed Central

Xie, Yijing; Martini, Nadja; Hassler, Christina; Kirch, Robert D.; Stieglitz, Thomas; Seifert, Andreas; Hofmann, Ulrich G.

2014-01-01

In neural prosthetics and stereotactic neurosurgery, intracortical electrodes are often utilized for delivering therapeutic electrical pulses, and recording neural electrophysiological signals. Unfortunately, neuroinflammation impairs the neuron-electrode-interface by developing a compact glial encapsulation around the implants in long term. At present, analyzing this immune reaction is only feasible with post-mortem histology; currently no means for specific in vivo monitoring exist and most applicable imaging modalities can not provide information in deep brain regions. Optical coherence tomography (OCT) is a well established imaging modality for in vivo studies, providing cellular resolution and up to 1.2 mm imaging depth in brain tissue. A fiber based spectral domain OCT was shown to be capable of minimally invasive brain imaging. In the present study, we propose to use a fiber based spectral domain OCT to monitor the progression of the tissue's immune response through scar encapsulation progress in a rat animal model. A fine fiber catheter was implanted in rat brain together with a flexible polyimide microelectrode in sight both of which acts as a foreign body and induces the brain tissue immune reaction. OCT signals were collected from animals up to 12 weeks after implantation and thus gliotic scarring in vivo monitored for that time. Preliminary data showed a significant enhancement of the OCT backscattering signal during the first 3 weeks after implantation, and increased attenuation factor of the sampled tissue due to the glial scar formation. PMID:25191264

Design, fabrication, and packaging of an integrated, wirelessly-powered optrode array for optogenetics application

PubMed Central

Kwon, Ki Yong; Lee, Hyung-Min; Ghovanloo, Maysam; Weber, Arthur; Li, Wen

2015-01-01

The recent development of optogenetics has created an increased demand for advancing engineering tools for optical modulation of neural circuitry. This paper details the design, fabrication, integration, and packaging procedures of a wirelessly-powered, light emitting diode (LED) coupled optrode neural interface for optogenetic studies. The LED-coupled optrode array employs microscale LED (μLED) chips and polymer-based microwaveguides to deliver light into multi-level cortical networks, coupled with microelectrodes to record spontaneous changes in neural activity. An integrated, implantable, switched-capacitor based stimulator (SCS) system provides high instantaneous power to the μLEDs through an inductive link to emit sufficient light and evoke neural activities. The presented system is mechanically flexible, biocompatible, miniaturized, and lightweight, suitable for chronic implantation in small freely behaving animals. The design of this system is scalable and its manufacturing is cost effective through batch fabrication using microelectromechanical systems (MEMS) technology. It can be adopted by other groups and customized for specific needs of individual experiments. PMID:25999823

A novel alternating current multiple array electrothermal micropump for lab-on-a-chip applications.

PubMed

Salari, A; Navi, M; Dalton, C

2015-01-01

The AC electrothermal technique is very promising for biofluid micropumping, due to its ability to pump high conductivity fluids. However, compared to electroosmotic micropumps, a lack of high fluid flow is a disadvantage. In this paper, a novel AC multiple array electrothermal (MAET) micropump, utilizing multiple microelectrode arrays placed on the side-walls of the fluidic channel of the micropump, is introduced. Asymmetric coplanar microelectrodes are placed on all sides of the microfluidic channel, and are actuated in different phases: one, two opposing, two adjacent, three, or all sides at the same time. Micropumps with different combinations of side electrodes and cross sections are numerically investigated in this paper. The effect of the governing parameters with respect to thermal, fluidic, and electrical properties are studied and discussed. To verify the simulations, the AC MAET concept was then fabricated and experimentally tested. The resulted fluid flow achieved by the experiments showed good agreement with the corresponding simulations. The number of side electrode arrays and the actuation patterns were also found to greatly influence the micropump performance. This study shows that the new multiple array electrothermal micropump design can be used in a wide range of applications such as drug delivery and lab-on-a-chip, where high flow rate and high precision micropumping devices for high conductivity fluids are needed.

Pulse Voltammetry in Single Cells Using Platinum Microelectrodes

DTIC Science & Technology

1991-11-22

E. and the range for Ed in multiple pulse voltammetry can be chosen from examination of voltammograms obtained by cyclic voltammetry or lin-ir sweep ... voltametry [3,13]. As pointed out by Sinru et al. [14) the potential and time of each pulse has a direct effect on the nature of the voltammetry

Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates

PubMed Central

Barrese, James C; Rao, Naveen; Paroo, Kaivon; Triebwasser, Corey; Vargas-Irwin, Carlos; Franquemont, Lachlan; Donoghue, John P

2016-01-01

Objective Brain–computer interfaces (BCIs) using chronically implanted intracortical microelectrode arrays (MEAs) have the potential to restore lost function to people with disabilities if they work reliably for years. Current sensors fail to provide reliably useful signals over extended periods of time for reasons that are not clear. This study reports a comprehensive retrospective analysis from a large set of implants of a single type of intracortical MEA in a single species, with a common set of measures in order to evaluate failure modes. Approach Since 1996, 78 silicon MEAs were implanted in 27 monkeys (Macaca mulatta). We used two approaches to find reasons for sensor failure. First, we classified the time course leading up to complete recording failure as acute (abrupt) or chronic (progressive). Second, we evaluated the quality of electrode recordings over time based on signal features and electrode impedance. Failure modes were divided into four categories: biological, material, mechanical, and unknown. Main results Recording duration ranged from 0 to 2104 days (5.75 years), with a mean of 387 days and a median of 182 days (n = 78). Sixty-two arrays failed completely with a mean time to failure of 332 days (median = 133 days) while nine array experiments were electively terminated for experimental reasons (mean = 486 days). Seven remained active at the close of this study (mean = 753 days). Most failures (56%) occurred within a year of implantation, with acute mechanical failures the most common class (48%), largely because of connector issues (83%). Among grossly observable biological failures (24%), a progressive meningeal reaction that separated the array from the parenchyma was most prevalent (14.5%). In the absence of acute interruptions, electrode recordings showed a slow progressive decline in spike amplitude, noise amplitude, and number of viable channels that predicts complete signal loss by about eight years. Impedance measurements showed systematic early increases, which did not appear to affect recording quality, followed by a slow decline over years. The combination of slowly falling impedance and signal quality in these arrays indicate that insulating material failure is the most significant factor. Significance This is the first long-term failure mode analysis of an emerging BCI technology in a large series of non-human primates. The classification system introduced here may be used to standardize how neuroprosthetic failure modes are evaluated. The results demonstrate the potential for these arrays to record for many years, but achieving reliable sensors will require replacing connectors with implantable wireless systems, controlling the meningeal reaction, and improving insulation materials. These results will focus future research in order to create clinical neuroprosthetic sensors, as well as valuable research tools, that are able to safely provide reliable neural signals for over a decade. PMID:24216311

Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates

NASA Astrophysics Data System (ADS)

Barrese, James C.; Rao, Naveen; Paroo, Kaivon; Triebwasser, Corey; Vargas-Irwin, Carlos; Franquemont, Lachlan; Donoghue, John P.

2013-12-01

Objective. Brain-computer interfaces (BCIs) using chronically implanted intracortical microelectrode arrays (MEAs) have the potential to restore lost function to people with disabilities if they work reliably for years. Current sensors fail to provide reliably useful signals over extended periods of time for reasons that are not clear. This study reports a comprehensive retrospective analysis from a large set of implants of a single type of intracortical MEA in a single species, with a common set of measures in order to evaluate failure modes. Approach. Since 1996, 78 silicon MEAs were implanted in 27 monkeys (Macaca mulatta). We used two approaches to find reasons for sensor failure. First, we classified the time course leading up to complete recording failure as acute (abrupt) or chronic (progressive). Second, we evaluated the quality of electrode recordings over time based on signal features and electrode impedance. Failure modes were divided into four categories: biological, material, mechanical, and unknown. Main results. Recording duration ranged from 0 to 2104 days (5.75 years), with a mean of 387 days and a median of 182 days (n = 78). Sixty-two arrays failed completely with a mean time to failure of 332 days (median = 133 days) while nine array experiments were electively terminated for experimental reasons (mean = 486 days). Seven remained active at the close of this study (mean = 753 days). Most failures (56%) occurred within a year of implantation, with acute mechanical failures the most common class (48%), largely because of connector issues (83%). Among grossly observable biological failures (24%), a progressive meningeal reaction that separated the array from the parenchyma was most prevalent (14.5%). In the absence of acute interruptions, electrode recordings showed a slow progressive decline in spike amplitude, noise amplitude, and number of viable channels that predicts complete signal loss by about eight years. Impedance measurements showed systematic early increases, which did not appear to affect recording quality, followed by a slow decline over years. The combination of slowly falling impedance and signal quality in these arrays indicates that insulating material failure is the most significant factor. Significance. This is the first long-term failure mode analysis of an emerging BCI technology in a large series of non-human primates. The classification system introduced here may be used to standardize how neuroprosthetic failure modes are evaluated. The results demonstrate the potential for these arrays to record for many years, but achieving reliable sensors will require replacing connectors with implantable wireless systems, controlling the meningeal reaction, and improving insulation materials. These results will focus future research in order to create clinical neuroprosthetic sensors, as well as valuable research tools, that are able to safely provide reliable neural signals for over a decade.

Improving Impedance of Implantable Microwire Multi-Electrode Arrays by Ultrasonic Electroplating of Durable Platinum Black

PubMed Central

Desai, Sharanya Arcot; Rolston, John D.; Guo, Liang; Potter, Steve M.

2010-01-01

Implantable microelectrode arrays (MEAs) have been a boon for neural stimulation and recording experiments. Commercially available MEAs have high impedances, due to their low surface area and small tip diameters, which are suitable for recording single unit activity. Lowering the electrode impedance, but preserving the small diameter, would provide a number of advantages, including reduced stimulation voltages, reduced stimulation artifacts and improved signal-to-noise ratio. Impedance reductions can be achieved by electroplating the MEAs with platinum (Pt) black, which increases the surface area but has little effect on the physical extent of the electrodes. However, because of the low durability of Pt black plating, this method has not been popular for chronic use. Sonicoplating (i.e. electroplating under ultrasonic agitation) has been shown to improve the durability of Pt black on the base metals of macro-electrodes used for cyclic voltammetry. This method has not previously been characterized for MEAs used in chronic neural implants. We show here that sonicoplating can lower the impedances of microwire multi-electrode arrays (MMEA) by an order of magnitude or more (depending on the time and voltage of electroplating), with better durability compared to pulsed plating or traditional DC methods. We also show the improved stimulation and recording performance that can be achieved in an in vivo implantation study with the sonicoplated low-impedance MMEAs, compared to high-impedance unplated electrodes. PMID:20485478

A Tapered Aluminium Microelectrode Array for Improvement of Dielectrophoresis-Based Particle Manipulation

PubMed Central

Buyong, Muhamad Ramdzan; Larki, Farhad; Faiz, Mohd Syafiq; Hamzah, Azrul Azlan; Yunas, Jumrail; Majlis, Burhanuddin Yeop

2015-01-01

In this work, the dielectrophoretic force (FDEP) response of Aluminium Microelectrode Arrays with tapered profile is investigated through experimental measurements and numerical simulations. A standard CMOS processing technique with a step for the formation of a tapered profile resist is implemented in the fabrication of Tapered Aluminium Microelectrode Arrays (TAMA). The FDEP is investigated through analysis of the Clausius-Mossotti factor (CMF) and cross-over frequency (fxo). The performance of TAMA with various side wall angles is compared to that of microelectrodes with a straight cut sidewall profile over a wide range of frequencies through FEM numerical simulations. Additionally, electric field measurement (EFM) is performed through scanning probe microscopy (SPM) in order to obtain the region of force focus in both platforms. Results showed that the tapered profile microelectrodes with angles between 60° and 70° produce the highest electric field gradient on the particles. Also, the region of the strongest electric field in TAMA is located at the bottom and top edge of microelectrode while the strongest electric field in microelectrodes with straight cut profile is found at the top corner of the microelectrode. The latter property of microelectrodes improves the probability of capturing/repelling the particles at the microelectrode’s side wall. PMID:25970255

Miniaturized redox potential probe for in situ environmental monitoring.

PubMed

Jang, Am; Lee, Jin-Hwan; Bhadri, Prashant R; Kumar, Suresh A; Timmons, William; Beyette, Fred R; Papautsky, Ian; Bishop, Paul L

2005-08-15

The need for accurate, robust in situ microscale monitoring of oxidation-reduction potentials (ORP) is required for continuous soil pore water quality monitoring. We are developing a suite of self-contained microelectrodes that can be used in the environment, such as at Superfund sites, to monitor ORP in contaminated soils and sediments. This paper presents details on our development of microelectrode sensor arrays for ORP measurements. The electrochemical performance of these ORP electrodes was fully characterized by measuring redox potentials in standard solutions. It found that the newly developed integrated ORP microelectrodes produced a very stable voltage response (the corresponding rate of the integrated microelectrode potential change was in the range of 0.6-1.1 mV/min), even when the measurement was carried out outside of a Faraday cage where signals from most conventional microelectrodes are usually inhibited by external electrical nose. These new microelectrodes were easier to fabricate and were more robust than conventional microelectrodes. The tip size of the integrated ORP microelectrode was approximately 200 nm square, with a taper angle of approximately 20 degrees and a length of 57 microm. The integrated ORP microelectrode exhibited better signal stability and substantially shorter response times (from less than a few milliseconds to 30 s, depending on the standard solution used) than the commercial millielectrode (a few minutes). Compared with the slope of the commercial millelectrode, the slope of the integrated microelectrode (61.5 mV/pH) was closerto the ideal slope against quinhydrone calibration solutions. Therefore, it is to be expected that the newly developed ORP microelectrode may have wider applications in contaminated soils, biofilms, and sediments.

Prognosis after treatment with multiple dental implants under general anesthesia and sedation in a cerebral palsy patient with mental retardation: A case report.

PubMed

Hong, Young-Joon; Dan, Jung-Bae; Kim, Myung-Jin; Kim, Hyun Jeong; Seo, Kwang-Suk

2017-06-01

Cerebral palsy is a non-progressive disorder resulting from central nervous system damage caused by multiple factors. Almost all cerebral palsy patients have a movement disorder that makes dental treatment difficult. Oral hygiene management is difficult and the risks for periodontitis, dental caries and loss of multiple teeth are high. Placement of dental implants for multiple missing teeth in cerebral palsy patients needs multiple rounds of general anesthesia, and the prognosis is poor despite the expense. Therefore, making the decision to perform multiple dental implant treatments on cerebral palsy patients is difficult. A 33-year-old female patient with cerebral palsy and mental retardation was scheduled for multiple implant treatments. She underwent computed tomography (CT) under sedation and the operation of nine dental implants under general anesthesia. Implant-supported fixed prosthesis treatment was completed. During follow-up, she had the anterior incisors extracted and underwent the surgery of 3 additional dental implants, completing the prosthetic treatment. Although oral parafunctions existed due to cerebral palsy, no implant failure was observed 9 years after the first implant surgery.

Potential for unreliable interpretation of EEG recorded with microelectrodes.

PubMed

Stacey, William C; Kellis, Spencer; Greger, Bradley; Butson, Christopher R; Patel, Paras R; Assaf, Trevor; Mihaylova, Temenuzhka; Glynn, Simon

2013-08-01

Recent studies in epilepsy, cognition, and brain machine interfaces have shown the utility of recording intracranial electroencephalography (iEEG) with greater spatial resolution. Many of these studies utilize microelectrodes connected to specialized amplifiers that are optimized for such recordings. We recently measured the impedances of several commercial microelectrodes and demonstrated that they will distort iEEG signals if connected to clinical EEG amplifiers commonly used in most centers. In this study we demonstrate the clinical implications of this effect and identify some of the potential difficulties in using microelectrodes. Human iEEG data were digitally filtered to simulate the signal recorded by a hybrid grid (two macroelectrodes and eight microelectrodes) connected to a standard EEG amplifier. The filtered iEEG data were read by three trained epileptologists, and high frequency oscillations (HFOs) were detected with a well-known algorithm. The filtering method was verified experimentally by recording an injected EEG signal in a saline bath with the same physical acquisition system used to generate the model. Several electrodes underwent scanning electron microscopy (SEM). Macroelectrode recordings were unaltered compared to the source iEEG signal, but microelectrodes attenuated low frequencies. The attenuated signals were difficult to interpret: all three clinicians changed their clinical scoring of slowing and seizures when presented with the same data recorded on different sized electrodes. The HFO detection algorithm was oversensitive with microelectrodes, classifying many more HFOs than when the same data were recorded with macroelectrodes. In addition, during experimental recordings the microelectrodes produced much greater noise as well as large baseline fluctuations, creating sharply contoured transients, and superimposed "false" HFOs. SEM of these microelectrodes demonstrated marked variability in exposed electrode surface area, lead fractures, and sharp edges. Microelectrodes should not be used with low impedance (<1 GΩ) amplifiers due to severe signal attenuation and variability that changes clinical interpretations. The current method of preparing microelectrodes can leave sharp edges and nonuniform amounts of exposed wire. Even when recorded with higher impedance amplifiers, microelectrode data are highly prone to artifacts that are difficult to interpret. Great care must be taken when analyzing iEEG from high impedance microelectrodes. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Assessment of brain-machine interfaces from the perspective of people with paralysis.

PubMed

Blabe, Christine H; Gilja, Vikash; Chestek, Cindy A; Shenoy, Krishna V; Anderson, Kim D; Henderson, Jaimie M

2015-08-01

One of the main goals of brain-machine interface (BMI) research is to restore function to people with paralysis. Currently, multiple BMI design features are being investigated, based on various input modalities (externally applied and surgically implantable sensors) and output modalities (e.g. control of computer systems, prosthetic arms, and functional electrical stimulation systems). While these technologies may eventually provide some level of benefit, they each carry associated burdens for end-users. We sought to assess the attitudes of people with paralysis toward using various technologies to achieve particular benefits, given the burdens currently associated with the use of each system. We designed and distributed a technology survey to determine the level of benefit necessary for people with tetraplegia due to spinal cord injury to consider using different technologies, given the burdens currently associated with them. The survey queried user preferences for 8 BMI technologies including electroencephalography, electrocorticography, and intracortical microelectrode arrays, as well as a commercially available eye tracking system for comparison. Participants used a 5-point scale to rate their likelihood to adopt these technologies for 13 potential control capabilities. Survey respondents were most likely to adopt BMI technology to restore some of their natural upper extremity function, including restoration of hand grasp and/or some degree of natural arm movement. High speed typing and control of a fast robot arm were also of interest to this population. Surgically implanted wireless technologies were twice as 'likely' to be adopted as their wired equivalents. Assessing end-user preferences is an essential prerequisite to the design and implementation of any assistive technology. The results of this survey suggest that people with tetraplegia would adopt an unobtrusive, autonomous BMI system for both restoration of upper extremity function and control of external devices such as communication interfaces.

Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems—A Simulation Study

PubMed Central

Johansson, Johannes; Wårdell, Karin; Hemm, Simone

2018-01-01

The success of deep brain stimulation (DBS) relies primarily on the localization of the implanted electrode. Its final position can be chosen based on the results of intraoperative microelectrode recording (MER) and stimulation tests. The optimal position often differs from the final one selected for chronic stimulation with the DBS electrode. The aim of the study was to investigate, using finite element method (FEM) modeling and simulations, whether lead design, electrical setup, and operating modes induce differences in electric field (EF) distribution and in consequence, the clinical outcome. Finite element models of a MER system and a chronic DBS lead were developed. Simulations of the EF were performed for homogenous and patient-specific brain models to evaluate the influence of grounding (guide tube vs. stimulator case), parallel MER leads, and non-active DBS contacts. Results showed that the EF is deformed depending on the distance between the guide tube and stimulating contact. Several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution. The DBS EF volume can cover the intraoperatively produced EF, but can also extend to other anatomical areas. In conclusion, EF deformations between stimulation tests and DBS should be taken into consideration as they can alter the clinical outcome. PMID:29415442

Co-deposition of carbon dots and reduced graphene oxide nanosheets on carbon-fiber microelectrode surface for selective detection of dopamine

NASA Astrophysics Data System (ADS)

Fang, Jian; Xie, Zhigang; Wallace, Gordon; Wang, Xungai

2017-08-01

In this work, carbon dots (CD) decorated graphene oxide (GO) nanosheets were electrochemically reduced and deposited onto carbon fiber (CF) to fabricate microelectrodes for highly sensitive and selective dopamine (DA) detection, in the presence of ascorbic acid (AA) and uric acid (UA). The results have shown that surface modification considerably increases the electrocatalytic activity of the carbon fiber microelectrode. Due to possible aggregation of the rGO sheets during deposition, modifying the microelectrode surface with rGO sheets alone cannot achieve the selectivity required for simultaneous detection of DA, AA and UA. Through attaching CD onto GO sheets, the rGO + CD/CF microelectrode performance was significantly improved. The existence of CD on GO sheets can effectively avoid inter-layer stacking of the rGO sheets and provide increased surface area for neurotransmitter-electrode interaction enhancement. The CD can also increase the charge storage capacity of GO sheets. This is the first report on applying both CD and rGO for surface modification of carbon fiber microelectrode. The rGO + CD/CF microelectrode has achieved a linear DA detection concentration range of 0.1-100 μM, with a detection limit of 0.02 μM. The sensitivity of the microelectrode towards DA was as high as 6.5 nA/μM, which is significantly higher than previously reported carbon fiber microelectrodes. The highly sensitive all-carbon based microelectrodes should find use in a number of biomedical applications, such as neurotransmitter detection, neural signal recording and cell physiology studies.

Microelectrodes in microbial ecology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boots, S.

1989-03-15

Understanding the microenvironment of bacteria has presented many challenges for the microbial ecologist. Simple intracellular capillary electrodes have been used in neurophysiology since the 1950s to measure action potentials in ion transport over biological membranes, and ion-selective electrodes were developed soon thereafter for the determination of H{sup +}, Na{sup +}, K{sup +}, and Ca{sup 2+}. However, these analytical techniques did not receive much attention until 1978, when Niels Peter Revsbech and Bo Barker Joergensen at the Institute of Ecology and Genetics, University of Aarhus, Denmark, began using oxygen microelectrodes in their studies of the ecology and biogeochemistry of marine sedimentsmore » and other microbial environments. Today, Revsbech and Joergensen use five types of microelectrodes, two types of oxygen microelectrodes, a combined microelectrode for nitrous oxide and oxygen, a sulfide microelectrode, and a pH microelectrode. The first three microelectrodes have diameters of about 10 {mu}m and the last two of about 50 {mu}m. Some of the electrodes actually contain two or three cathodes plus a reference electrode, all situated behind a polymer membrane. In situ experiments have been done for several years at a water depth of several meters, where the micromanipulator is operated by a diver. Recently measurements were obtained in the deep sea with the microelectrodes mounted on a free-falling vehicle or operated from a submersible vessel.« less

A cochlear implant fabricated using a bulk silicon-surface micromachining process

NASA Astrophysics Data System (ADS)

Bell, Tracy Elizabeth

1999-11-01

This dissertation presents the design and fabrication of two generations of a silicon microelectrode array for use in a cochlear implant. A cochlear implant is a device that is inserted into the inner ear and uses electrical stimulation to provide sound sensations to the profoundly deaf. The first-generation silicon cochlear implant is a passive device fabricated using silicon microprobe technology developed at the University of Michigan. It contains twenty-two iridium oxide (IrO) stimulating sites that are 250 mum in diameter and spaced at 750 mum intervals. In-vivo recordings were made in guinea pig auditory cortex in response to electrical stimulation with this device, verifying its ability to electrically evoke an auditory response. Auditory thresholds as low as 78 muA were recorded. The second-generation implant is a thirty-two site, four-channel device with on-chip CMOS site-selection circuitry and integrated position sensing. It was fabricated using a novel bulk silicon surface micromachining process which was developed as a part of this dissertation work. While the use of semiconductor technology offers many advantages in fabricating cochlear implants over the methods currently used, it was felt that even further advantages could be gained by developing a new micromachining process which would allow circuitry to be distributed along the full length of the cochlear implant substrate. The new process uses electropolishing of an n+ bulk silicon sacrificial layer to undercut and release n- epitaxial silicon structures from the wafer. An extremely abrupt etch-stop between the n+ and n- silicon is obtained, with no electropolishing taking place in the n-type silicon that is doped lower than 1 x 1017 cm-3 in concentration. Lateral electropolishing rates of up to 50 mum/min were measured using this technique, allowing one millimeter-wide structures to be fully undercut in as little as 10 minutes. The new micromachining process was integrated with a standard p-well CMOS integrated circuit process to fabricate the second-generation active silicon cochlear implants.

Prediction of Imagined Single-Joint Movements in a Person with High Level Tetraplegia

PubMed Central

Simeral, John D.; Donoghue, John P.; Hochberg, Leigh R.; Kirsch, Robert F.

2013-01-01

Cortical neuroprostheses for movement restoration require developing models for relating neural activity to desired movement. Previous studies have focused on correlating single-unit activities (SUA) in primary motor cortex to volitional arm movements in able-bodied primates. The extent of the cortical information relevant to arm movements remaining in severely paralyzed individuals is largely unknown. We record intracortical signals using a microelectrode array chronically implanted in the precentral gyrus of a person with tetraplegia, and estimate positions of imagined single-joint arm movements. Using visually guided motor imagery, the participant imagined performing eight distinct single-joint arm movements while SUA, multi-spike trains (MSP), multi-unit activity (MUA), and local field potential time (LFPrms) and frequency signals (LFPstft) were recorded. Using linear system identification, imagined joint trajectories were estimated with 20 – 60% variance explained, with wrist flexion/extension predicted the best and pronation/supination the poorest. Statistically, decoding of MSP and LFPstft yielded estimates that equaled those of SUA. Including multiple signal types in a decoder increased prediction accuracy in all cases. We conclude that signals recorded from a single restricted region of the precentral gyrus in this person with tetraplegia contained useful information regarding the intended movements of upper extremity joints. PMID:22851229

A hardware-algorithm co-design approach to optimize seizure detection algorithms for implantable applications.

PubMed

Raghunathan, Shriram; Gupta, Sumeet K; Markandeya, Himanshu S; Roy, Kaushik; Irazoqui, Pedro P

2010-10-30

Implantable neural prostheses that deliver focal electrical stimulation upon demand are rapidly emerging as an alternate therapy for roughly a third of the epileptic patient population that is medically refractory. Seizure detection algorithms enable feedback mechanisms to provide focally and temporally specific intervention. Real-time feasibility and computational complexity often limit most reported detection algorithms to implementations using computers for bedside monitoring or external devices communicating with the implanted electrodes. A comparison of algorithms based on detection efficacy does not present a complete picture of the feasibility of the algorithm with limited computational power, as is the case with most battery-powered applications. We present a two-dimensional design optimization approach that takes into account both detection efficacy and hardware cost in evaluating algorithms for their feasibility in an implantable application. Detection features are first compared for their ability to detect electrographic seizures from micro-electrode data recorded from kainate-treated rats. Circuit models are then used to estimate the dynamic and leakage power consumption of the compared features. A score is assigned based on detection efficacy and the hardware cost for each of the features, then plotted on a two-dimensional design space. An optimal combination of compared features is used to construct an algorithm that provides maximal detection efficacy per unit hardware cost. The methods presented in this paper would facilitate the development of a common platform to benchmark seizure detection algorithms for comparison and feasibility analysis in the next generation of implantable neuroprosthetic devices to treat epilepsy. Copyright © 2010 Elsevier B.V. All rights reserved.

Highly Doped Polycrystalline Silicon Microelectrodes Reduce Noise in Neuronal Recordings In Vivo

PubMed Central

Saha, Rajarshi; Jackson, Nathan; Patel, Chetan; Muthuswamy, Jit

2013-01-01

The aims of this study are to 1) experimentally validate for the first time the nonlinear current-potential characteristics of bulk doped polycrystalline silicon in the small amplitude voltage regimes (0–200 μV) and 2) test if noise amplitudes (0–15 μV) from single neuronal electrical recordings get selectively attenuated in doped polycrystalline silicon microelectrodes due to the above property. In highly doped polycrystalline silicon, bulk resistances of several hundred kilo-ohms were experimentally measured for voltages typical of noise amplitudes and 9–10 kΩ for voltages typical of neural signal amplitudes (>150–200 μV). Acute multiunit measurements and noise measurements were made in n = 6 and n = 8 anesthetized adult rats, respectively, using polycrystalline silicon and tungsten microelectrodes. There was no significant difference in the peak-to-peak amplitudes of action potentials recorded from either microelectrode (p > 0.10). However, noise power in the recordings from tungsten microelectrodes (26.36 ± 10.13 pW) was significantly higher (p < 0.001) than the corresponding value in polycrystalline silicon microelectrodes (7.49 ± 2.66 pW). We conclude that polycrystalline silicon microelectrodes result in selective attenuation of noise power in electrical recordings compared to tungsten microelectrodes. This reduction in noise compared to tungsten microelectrodes is likely due to the exponentially higher bulk resistances offered by highly doped bulk polycrystalline silicon in the range of voltages corresponding to noise in multiunit measurements. PMID:20667815

Low-loss microelectrodes fabricated using reverse-side exposure for a tunable ferroelectric capacitor application

NASA Astrophysics Data System (ADS)

Yoon, Yong-Kyu; Stevenson Kenney, J.; Hunt, Andrew T.; Allen, Mark G.

2006-02-01

Narrowly spaced thick microelectrodes are fabricated using a self-aligned multiple reverse-side exposure scheme for an improved quality-factor tunable ferroelectric capacitor. The microelectrodes are fabricated on a functional substrate—a thin film ferroelectric (barium strontium titanate, BST; BaxSr1-xTiO3) coated sapphire substrate, which has an electric-field-dependent dielectric property providing tuning functionality, as well as UV transparency permitting an additional degree of freedom in photolithography steps. The microelectrode process has been applied to interdigitated capacitor fabrication, where a critical challenge is maintaining narrow gaps between electrodes for high tunability, while simultaneously forming thick electrodes to minimize conductor loss. A single mask, self-aligned reverse-side exposure through the transparent substrate achieves both these goals. A single-finger test capacitor with an electrode gap of 1.2 µm and an electrode thickness of 2.2 µm is fabricated and characterized. Tunability (T = 100 × (C0 - Cbias)/C0) of 33% at 10 V has been achieved at 100 kHz. The 2.2 µm thick structure shows improvement of Q-factor compared to that of a 0.1 µm thick structure. To demonstrate the scalability of this process, a 102-finger interdigitated capacitor is fabricated and characterized at 100 kHz and 1 GHz. The structure is embedded in a 25 µm thick epoxy resin SU-8 for passivation. A quality factor decrease of 15-25%, tunability decrease of 2-3% and capacitance increase of 6% are observed due to the expoxy resin after passivation. High frequency performance of the capacitor has been measured to be 15.9 pF of capacitance, 28.1% tunability at 10 V and a quality factor of 16 (at a 10 V dc bias) at 1 GHz.

Vertically aligned carbon nanotubes for microelectrode arrays applications.

PubMed

Castro Smirnov, J R; Jover, Eric; Amade, Roger; Gabriel, Gemma; Villa, Rosa; Bertran, Enric

2012-09-01

In this work a methodology to fabricate carbon nanotube based electrodes using plasma enhanced chemical vapour deposition has been explored and defined. The final integrated microelectrode based devices should present specific properties that make them suitable for microelectrode arrays applications. The methodology studied has been focused on the preparation of highly regular and dense vertically aligned carbon nanotube (VACNT) mat compatible with the standard lithography used for microelectrode arrays technology.

Use of microelectrodes for electrochemical measurement of nitric oxide in natural seawater

NASA Astrophysics Data System (ADS)

Zhang, Zhengbin; Xing, Lei; Cai, Weijun; Ren, Chunyan; Jiang, Liqing

2004-12-01

In this paper, the application of a homemade Nafion and Co(Salen) modified platinum microelectrode and an ISO-NOPMC microsensor (World Precision Instruments, USA) to measure nitric oxide in natural seawater is reported. These two microelectrodes are suitable for the measurement. In natural seawater, the sensitivity and stability of the ISO-NOPMC microsensor are higher than that of the homemade Nafion and Co(Salen) modified platinum microelectrode.

Surface-enhanced Raman spectroscopy on litographically constructed microelectrodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhelyaskov, V.R.; Milne, E.T.; Weldon, M.K.

1995-12-31

A novel silicon substrate microelectrode array has been demonstrated to function as a surface-enhanced Raman Spectroscopy (SERS) microelectrode. SERS from adenosine and pyridine down to 10 mM concentration on silver coated iridium and gold microelectrode arrays have been observed with excitation at 532 nm and 633 nm correspondingly. Ag/AgCl reference electrode and platinum or integrated on the microelectrode iridium counter electrodes were used. Owing to the small area of the activated sites on the microelectrode (10 mm x 15 mm) the SERS signal exhibited a strong laser power dependence. The optimal laser power on the activated site was shown tomore » be in the order of x 100 mW. Good quality SERS spectra were recorded with exposure times of 10s and less. The small size of the electrodes makes them promising for studies in confined spaces. This includes potential applications as capillary electrophoreses detectors and probes of chemistry of biological organisms. A work on detection of lipids adhered to self-organized monolayers (SAM)s of alkanethiols on the activated microelectrodes is in progress.« less

Gold ultra-microelectrode arrays: application to the steady-state voltammetry of hydroxide ion in aqueous solution.

PubMed

Ordeig, Olga; Banks, Craig E; Davies, Trevor J; del Campo, F Javier; Muñoz, Francesc Xavier; Compton, Richard G

2006-05-01

Gold ultra-microelectrode arrays are used to explore the electrochemical oxidation of hydroxide ions and are shown to be analytical useful. Two types of ultra-microelectrode arrays are used; the first consist of 256 individual electrodes of 5 microm in radius, 170 of which are electrochemically active in a cubic arrangement which are separated from their nearest neighbour by a distance of 100 microm. The second array compromises 2597 electrodes of 2.5 microm in radius and of which 1550 of which are electrochemically active in a hexagonal arrangement separated by the nearest neighbour by 55 microm. Well defined voltammetric waves are found with peak currents proportional to the concentration of hydroxide ions in the range 50 microM to 1 mM. Detection limits of 20 microM using the 170 ultra-microelectrode and 10 microM with the 1550 ultra-microelectrode array are shown to be possible but with a higher sensitivity of 4 mA M(-1) observed using the 1550 ultra-microelectrode array compared to 1.2 mA M(-1) with the 170 ultra-microelectrode array.

Data-driven model comparing the effects of glial scarring and interface interactions on chronic neural recordings in non-human primates

NASA Astrophysics Data System (ADS)

Malaga, Karlo A.; Schroeder, Karen E.; Patel, Paras R.; Irwin, Zachary T.; Thompson, David E.; Bentley, J. Nicole; Lempka, Scott F.; Chestek, Cynthia A.; Patil, Parag G.

2016-02-01

Objective. We characterized electrode stability over twelve weeks of impedance and neural recording data from four chronically-implanted Utah arrays in two rhesus macaques, and investigated the effects of glial scarring and interface interactions at the electrode recording site on signal quality using a computational model. Approach. A finite-element model of a Utah array microelectrode in neural tissue was coupled with a multi-compartmental model of a neuron to quantify the effects of encapsulation thickness, encapsulation resistivity, and interface resistivity on electrode impedance and waveform amplitude. The coupled model was then reconciled with the in vivo data. Histology was obtained seventeen weeks post-implantation to measure gliosis. Main results. From week 1-3, mean impedance and amplitude increased at rates of 115.8 kΩ/week and 23.1 μV/week, respectively. This initial ramp up in impedance and amplitude was observed across all arrays, and is consistent with biofouling (increasing interface resistivity) and edema clearing (increasing tissue resistivity), respectively, in the model. Beyond week 3, the trends leveled out. Histology showed that thin scars formed around the electrodes. In the model, scarring could not match the in vivo data. However, a thin interface layer at the electrode tip could. Despite having a large effect on impedance, interface resistivity did not have a noticeable effect on amplitude. Significance. This study suggests that scarring does not cause an electrical problem with regard to signal quality since it does not appear to be the main contributor to increasing impedance or significantly affect amplitude unless it displaces neurons. This, in turn, suggests that neural signals can be obtained reliably despite scarring as long as the recording site has sufficiently low impedance after accumulating a thin layer of biofouling. Therefore, advancements in microelectrode technology may be expedited by focusing on improvements to the recording site-tissue interface rather than elimination of the glial scar.

Versatile, modular 3D microelectrode arrays for neuronal ensemble recordings: from design to fabrication, assembly, and functional validation in non-human primates.

PubMed

Barz, F; Livi, A; Lanzilotto, M; Maranesi, M; Bonini, L; Paul, O; Ruther, P

2017-06-01

Application-specific designs of electrode arrays offer an improved effectiveness for providing access to targeted brain regions in neuroscientific research and brain machine interfaces. The simultaneous and stable recording of neuronal ensembles is the main goal in the design of advanced neural interfaces. Here, we describe the development and assembly of highly customizable 3D microelectrode arrays and demonstrate their recording performance in chronic applications in non-human primates. System assembly relies on a microfabricated stacking component that is combined with Michigan-style silicon-based electrode arrays interfacing highly flexible polyimide cables. Based on the novel stacking component, the lead time for implementing prototypes with altered electrode pitches is minimal. Once the fabrication and assembly accuracy of the stacked probes have been characterized, their recording performance is assessed during in vivo chronic experiments in awake rhesus macaques (Macaca mulatta) trained to execute reaching-grasping motor tasks. Using a single set of fabrication tools, we implemented three variants of the stacking component for electrode distances of 250, 300 and 350 µm in the stacking direction. We assembled neural probes with up to 96 channels and an electrode density of 98 electrodes mm -2 . Furthermore, we demonstrate that the shank alignment is accurate to a few µm at an angular alignment better than 1°. Three 64-channel probes were chronically implanted in two monkeys providing single-unit activity on more than 60% of all channels and excellent recording stability. Histological tissue sections, obtained 52 d after implantation from one of the monkeys, showed minimal tissue damage, in accordance with the high quality and stability of the recorded neural activity. The versatility of our fabrication and assembly approach should significantly support the development of ideal interface geometries for a broad spectrum of applications. With the demonstrated performance, these probes are suitable for both semi-chronic and chronic applications.

Versatile, modular 3D microelectrode arrays for neuronal ensemble recordings: from design to fabrication, assembly, and functional validation in non-human primates

NASA Astrophysics Data System (ADS)

Barz, F.; Livi, A.; Lanzilotto, M.; Maranesi, M.; Bonini, L.; Paul, O.; Ruther, P.

2017-06-01

Objective. Application-specific designs of electrode arrays offer an improved effectiveness for providing access to targeted brain regions in neuroscientific research and brain machine interfaces. The simultaneous and stable recording of neuronal ensembles is the main goal in the design of advanced neural interfaces. Here, we describe the development and assembly of highly customizable 3D microelectrode arrays and demonstrate their recording performance in chronic applications in non-human primates. Approach. System assembly relies on a microfabricated stacking component that is combined with Michigan-style silicon-based electrode arrays interfacing highly flexible polyimide cables. Based on the novel stacking component, the lead time for implementing prototypes with altered electrode pitches is minimal. Once the fabrication and assembly accuracy of the stacked probes have been characterized, their recording performance is assessed during in vivo chronic experiments in awake rhesus macaques (Macaca mulatta) trained to execute reaching-grasping motor tasks. Main results. Using a single set of fabrication tools, we implemented three variants of the stacking component for electrode distances of 250, 300 and 350 µm in the stacking direction. We assembled neural probes with up to 96 channels and an electrode density of 98 electrodes mm-2. Furthermore, we demonstrate that the shank alignment is accurate to a few µm at an angular alignment better than 1°. Three 64-channel probes were chronically implanted in two monkeys providing single-unit activity on more than 60% of all channels and excellent recording stability. Histological tissue sections, obtained 52 d after implantation from one of the monkeys, showed minimal tissue damage, in accordance with the high quality and stability of the recorded neural activity. Significance. The versatility of our fabrication and assembly approach should significantly support the development of ideal interface geometries for a broad spectrum of applications. With the demonstrated performance, these probes are suitable for both semi-chronic and chronic applications.

MRI directed bilateral stimulation of the subthalamic nucleus in patients with Parkinson's disease

PubMed Central

Patel, N; Plaha, P; O'Sullivan, K; McCarter, R; Heywood, P; Gill, S

2003-01-01

Objective: Bilateral chronic high frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) has emerged as an appropriate therapy for patients with advanced Parkinson's disease refractory to medical therapy. Advances in neuroimaging and neurophysiology have led to the development of varied targeting methods for the delivery of this treatment. Intraoperative neurophysiological and clinical monitoring is regarded by many to be mandatory for accurate STN localisation. We have examined efficacy of bilateral STN stimulation using a predominantly magnetic resonance imaging (MRI)-directed technique. Methods: DBS leads were stereotactically implanted into the STN using an MRI directed method, with intraoperative macrostimulation used purely for adjustment. The effects of DBS were evaluated in 16 patients followed up to 12 months, and compared with baseline assessments. Assessments were performed in both off and on medication states, and were based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests. Functional status outcomes were examined using the PDQ-39 quality of life questionnaire. A battery of psychometric tests was used to assess cognition. Results: After 12 months, stimulation in the off medication state resulted in significant improvements in Activities of Daily Living and Motor scores (UPDRS parts II and III) by 62% and 61% respectively. Timed motor tests were significantly improved in the off medication state. Motor scores (UPDRS part III) were significantly improved by 40% in the on medication state. Dyskinesias and off duration were significantly reduced and the mean dose of L-dopa equivalents was reduced by half. Psychometric test scores were mostly unchanged or improved. Adverse events were few. Conclusions: An MRI directed targeting method for implantation of DBS leads into the STN can be used safely and effectively, and results are comparable with studies using intraoperative microelectrode neurophysiological targeting. In addition, our method was associated with an efficient use of operating time, and without the necessary costs of microelectrode recording. PMID:14638880

In-situ imaging of chloride ions at the metal/solution interface by scanning combination microelectrodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, C.J.; Du, R.G.; Nguyen, T.

2000-01-01

Combination solid silver-silver chloride (Ag-AgCl) and liquid membrane Cl{sup {minus}} ion-selective microelectrodes were designed and constructed. These microelectrodes, which had a micrometer-sized tip, contained two compartments: one served as the reference electrode and the other as the Cl{sup {minus}} ion-selective electrode. The microelectrodes were used to map in-situ Cl{sup {minus}} ion distribution in several localized corrosion systems. When used with a computerized scanning stage, the microelectrodes provided information on the distribution of Cl{sup {minus}} ions near the metal/electrolyte interface. Cl{sup {minus}} ions were observed migrating toward and accumulating near the anodic region forming a Cl{sup {minus}}ion-rich island on the metalmore » surface. Scanning combination Cl{sup {minus}} ion-selective microelectrodes may provide a useful tool for mechanistic studies of localized corrosion.« less

Pacemakers and Implantable Defibrillators - Multiple Languages

MedlinePlus

... Multiple Languages → All Health Topics → Pacemakers and Implantable Defibrillators URL of this page: https://medlineplus.gov/languages/ ... List of All Topics All Pacemakers and Implantable Defibrillators - Multiple Languages To use the sharing features on ...

Effect of brain shift on the creation of functional atlases for deep brain stimulation surgery

PubMed Central

Pallavaram, Srivatsan; Remple, Michael S.; Neimat, Joseph S.; Kao, Chris; Konrad, Peter E.; D’Haese, Pierre-François

2011-01-01

Purpose In the recent past many groups have tried to build functional atlases of the deep brain using intra-operatively acquired information such as stimulation responses or micro-electrode recordings. An underlying assumption in building such atlases is that anatomical structures do not move between pre-operative imaging and intra-operative recording. In this study, we present evidences that this assumption is not valid. We quantify the effect of brain shift between pre-operative imaging and intra-operative recording on the creation of functional atlases using intra-operative somatotopy recordings and stimulation response data. Methods A total of 73 somatotopy points from 24 bilateral subthalamic nucleus (STN) implantations and 52 eye deviation stimulation response points from 17 bilateral STN implantations were used. These points were spatially normalized on a magnetic resonance imaging (MRI) atlas using a fully automatic non-rigid registration algorithm. Each implantation was categorized as having low, medium or large brain shift based on the amount of pneumocephalus visible on post-operative CT. The locations of somatotopy clusters and stimulation maps were analyzed for each category. Results The centroid of the large brain shift cluster of the somatotopy data (posterior, lateral, inferior: 3.06, 11.27, 5.36 mm) was found posterior, medial and inferior to that of the medium cluster (2.90, 13.57, 4.53 mm) which was posterior, medial and inferior to that of the low shift cluster (1.94, 13.92, 3.20 mm). The coordinates are referenced with respect to the mid-commissural point. Euclidean distances between the centroids were 1.68, 2.44 and 3.59 mm, respectively for low-medium, medium-large and low-large shift clusters. We found similar trends for the positions of the stimulation maps. The Euclidian distance between the highest probability locations on the low and medium-large shift maps was 4.06 mm. Conclusion The effect of brain shift in deep brain stimulation (DBS) surgery has been demonstrated using intra-operative somatotopy recordings as well as stimulation response data. The results not only indicate that considerable brain shift happens before micro-electrode recordings in DBS but also that brain shift affects the creation of accurate functional atlases. Therefore, care must be taken when building and using such atlases of intra-operative data and also when using intra-operative data to validate anatomical atlases. PMID:20033503

An Unsupervised Online Spike-Sorting Framework.

PubMed

Knieling, Simeon; Sridharan, Kousik S; Belardinelli, Paolo; Naros, Georgios; Weiss, Daniel; Mormann, Florian; Gharabaghi, Alireza

2016-08-01

Extracellular neuronal microelectrode recordings can include action potentials from multiple neurons. To separate spikes from different neurons, they can be sorted according to their shape, a procedure referred to as spike-sorting. Several algorithms have been reported to solve this task. However, when clustering outcomes are unsatisfactory, most of them are difficult to adjust to achieve the desired results. We present an online spike-sorting framework that uses feature normalization and weighting to maximize the distinctiveness between different spike shapes. Furthermore, multiple criteria are applied to either facilitate or prevent cluster fusion, thereby enabling experimenters to fine-tune the sorting process. We compare our method to established unsupervised offline (Wave_Clus (WC)) and online (OSort (OS)) algorithms by examining their performance in sorting various test datasets using two different scoring systems (AMI and the Adamos metric). Furthermore, we evaluate sorting capabilities on intra-operative recordings using established quality metrics. Compared to WC and OS, our algorithm achieved comparable or higher scores on average and produced more convincing sorting results for intra-operative datasets. Thus, the presented framework is suitable for both online and offline analysis and could substantially improve the quality of microelectrode-based data evaluation for research and clinical application.

Automated navigation of a glass micropipette on a high-density microelectrode array.

PubMed

Jing Lin; Obien, Marie Engelene J; Hierlemann, Andreas; Frey, Urs

2015-08-01

High-density microelectrode arrays (HDMEAs) provide the capability to monitor the extracellular electric potential of multiple neurons at subcellular resolution over extended periods of time. In contrast, patch clamp allows for intracellular, sub-threshold recordings from a single patched neuron for very limited time on the order of an hour. Therefore, it will be beneficial to combine HDMEA and patch clamp for simultaneous intra- and extracellular recording of neuronal activity. Previously, it has been shown that the HDMEA can be used to localize and steer a glass micropipette towards a target location without using an optical microscope [1]. Here, we present an automated system, implemented in LabVIEW, which automatically locates and moves the glass micropipette towards a user-defined target. The presented system constitutes a first step towards developing an automated system to navigate a pipette to patch a neuron in vitro.

Carbon nanotubes grown on metal microelectrodes for the detection of dopamine

DOE PAGES

Yang, Cheng; Jacobs, Christopher B.; Nguyen, Michael; ...

2015-12-07

Microelectrodes modified with carbon nanotubes (CNTs) are useful for the detection of neurotransmitters because the CNTs enhance sensitivity and have electrocatalytic effects. CNTs can be grown on carbon fiber microelectrodes (CFMEs) but the intrinsic electrochemical activity of carbon fibers makes evaluating the effect of CNT enhancement difficult. Metal wires are highly conductive and many metals have no intrinsic electrochemical activity for dopamine, so we investigated CNTs grown on metal wires as microelectrodes for neurotransmitter detection. In this work, we successfully grew CNTs on niobium substrates for the first time. Instead of planar metal surfaces, metal wires with a diameter ofmore » only 25 μm were used as CNT substrates; these have potential in tissue applications due to their minimal tissue damage and high spatial resolution. Scanning electron microscopy shows that aligned CNTs are grown on metal wires after chemical vapor deposition. By use of fast-scan cyclic voltammetry, CNT-coated niobium (CNT-Nb) microelectrodes exhibit higher sensitivity and lower ΔE p value compared to CNTs grown on carbon fibers or other metal wires. The limit of detection for dopamine at CNT-Nb microelectrodes is 11 ± 1 nM, which is approximately 2-fold lower than that of bare CFMEs. Adsorption processes were modeled with a Langmuir isotherm, and detection of other neurochemicals was also characterized, including ascorbic acid, 3,4-dihydroxyphenylacetic acid, serotonin, adenosine, and histamine. CNT-Nb microelectrodes were used to monitor stimulated dopamine release in anesthetized rats with high sensitivity. This research demonstrates that CNT-grown metal microelectrodes, especially CNTs grown on Nb microelectrodes, are useful for monitoring neurotransmitters.« less

EDITORIAL: Special issue containing contributions from the 39th Neural Interfaces Conference Special issue containing contributions from the 39th Neural Interfaces Conference

NASA Astrophysics Data System (ADS)

Weiland, James D.

2011-07-01

Implantable neural interfaces provide substantial benefits to individuals with neurological disorders. That was the unequivocal message delivered by speaker after speaker from the podium of the 39th Neural Interfaces Conference (NIC2010) held in Long Beach, California, in June 2010. Giving benefit to patients is the most important measure for any biomedical technology, and myriad presentations at NIC2010 made clear that implantable neurostimulation technology has achieved this goal. Cochlear implants allow deaf people to communicate through speech. Deep brain stimulators give back mobility and dexterity necessary for so many daily tasks that are often taken for granted. Chronic pain can be alleviated through spinal cord stimulation. Motor prosthesis systems have been demonstrated in humans, through both reanimation of paralyzed limbs and neural control of robotic arms. Earlier this year, a retinal prosthesis was approved for sale in Europe, providing some hope for the blind. In sum, current clinical implants have been tremendously beneficial for today's patients and experimental systems that will be translated to the clinic promise to expand the number of people helped through bioelectronic therapies. Yet there are significant opportunities for improvement. For sensory prostheses, patients report an artificial sensation, clearly different from the natural sensation they remember. Neuromodulation systems, such as deep brain stimulation and pain stimulators, often have side effects that are tolerated as long as the side effects are less impactful than the disease. The papers published in the special issue from NIC2010 reflect the maturing and expanding field of neural interfaces. Our field has moved past proof-of-principle demonstrations and is now focusing on proving the longevity required for clinical implementation of new devices, extending existing approaches to new diseases and improving current devices for better outcomes. Closed-loop neuromodulation is a strategy that can potentially optimize dosing, reduce side effects and extend implant battery life. The article by Liang et al investigates methods for closed loop control of epilepsy, using neural recording to detect imminent seizures and stimulation to halt the aberrant neural activity leading to seizure. Liu et al report on a model of basal ganglia function that could lead to optimized, closed-loop stimulation to reduce symptoms of Parkinson's disease while avoiding side effects. Our laboratory, as described in Ray et al, is investigating the interface between stimulating microelectrodes and the retina, to inform the design of a high-resolution retinal prosthesis. Three contributions address the issue of long-term stability of cortical recording, which remains a major hurdle to implementation of neural recording systems. The Utah group reports on the in vitro testing of a completely implantable, wireless neural recording system, demonstrating almost one year of reliable performance under simulated implant conditions. Shenoy's laboratory at Stanford demonstrates that useful signals can be recorded from research animals for over 2.5 years. Lempka et al describe a modeling approach to analyzing intracortical microelectrode recordings. These findings represent real and significant progress towards overcoming the final barriers to implementation of a reliable cortical interface. Planning is well underway for the 40th Neural Interfaces Conference, which will be held in Salt Lake City, Utah, in June 2012. The conference promises to continue the NIC tradition of showcasing the latest results from clinical trials of neural interface therapies while providing ample time for dynamic exchange amongst the interdisciplinary audience of engineers, scientists and clinicians.

High-density stretchable microelectrode arrays: An integrated technology platform for neural and muscular surface interfacing

NASA Astrophysics Data System (ADS)

Guo, Liang

2011-12-01

Numerous applications in neuroscience research and neural prosthetics, such as retinal prostheses, spinal-cord surface stimulation for prosthetics, electrocorticogram (ECoG) recording for epilepsy detection, etc., involve electrical interaction with soft excitable tissues using a surface stimulation and/or recording approach. These applications require an interface that is able to set up electrical communications with a high throughput between electronics and the excitable tissue and that can dynamically conform to the shape of the soft tissue. Being a compliant and biocompatible material with mechanical impedance close to that of soft tissues, polydimethylsiloxane (PDMS) offers excellent potential as the substrate material for such neural interfaces. However, fabrication of electrical functionalities on PDMS has long been very challenging. This thesis work has successfully overcome many challenges associated with PDMS-based microfabrication and achieved an integrated technology platform for PDMS-based stretchable microelectrode arrays (sMEAs). This platform features a set of technological advances: (1) we have fabricated uniform current density profile microelectrodes as small as 10 mum in diameter; (2) we have patterned high-resolution (feature as small as 10 mum), high-density (pitch as small as 20 mum) thin-film gold interconnects on PDMS substrate; (3) we have developed a multilayer wiring interconnect technology within the PDMS substrate to further boost the achievable integration density of such sMEA; and (4) we have invented a bonding technology---via-bonding---to facilitate high-resolution, high-density integration of the sMEA with integrated circuits (ICs) to form a compact implant. Taken together, this platform provides a high-resolution, high-density integrated system solution for neural and muscular surface interfacing. sMEAs of example designs are evaluated through in vitro and in vivo experimentations on their biocompatibility, surface conformability, and surface recording/stimulation capabilities, with a focus on epimysial (i.e. on the surface of muscle) applications. Finally, as an example medical application, we investigate a prosthesis for unilateral vocal cord paralysis (UVCP) based on simultaneous multichannel epimysial recording and stimulation.

Composite wire microelectrode and method of making same

DOE Office of Scientific and Technical Information (OSTI.GOV)

Isaacs, Hugh S.; Aldykiewicz, Jr., Antonio J.

1996-12-03

A composite wire microelectrode for making electro-chemical measurements, and method of making same. The microelectrode includes an inner conductive sensing wire and an outer tube that is oxidized to form a dielectric, self-healing oxide layer around the sensing wire.

Monochloramine Microelectrode for In-Situ Application Within Chloraminated Distribution System Biofilm

EPA Science Inventory

A monochloramine microelectrode with a tip size between 5 and 15 μm and using platinum wire was successfully designed, fabricated and characterized for in-situ monochloramine measurement within chloraminated distribution system biofilm. The monochloramine microelectrode showed s...

A highly compliant serpentine shaped polyimide interconnect for front-end strain relief in chronic neural implants.

PubMed

Sankar, Viswanath; Sanchez, Justin C; McCumiskey, Edward; Brown, Nagid; Taylor, Curtis R; Ehlert, Gregory J; Sodano, Henry A; Nishida, Toshikazu

2013-01-01

While the signal quality of recording neural electrodes is observed to degrade over time, the degradation mechanisms are complex and less easily observable. Recording microelectrodes failures are attributed to different biological factors such as tissue encapsulation, immune response, and disruption of blood-brain barrier (BBB) and non-biological factors such as strain due to micromotion, insulation delamination, corrosion, and surface roughness on the recording site (1-4). Strain due to brain micromotion is considered to be one of the important abiotic factors contributing to the failure of the neural implants. To reduce the forces exerted by the electrode on the brain, a high compliance 2D serpentine shaped electrode cable was designed, simulated, and measured using polyimide as the substrate material. Serpentine electrode cables were fabricated using MEMS microfabrication techniques, and the prototypes were subjected to load tests to experimentally measure the compliance. The compliance of the serpentine cable was numerically modeled and quantitatively measured to be up to 10 times higher than the compliance of a straight cable of same dimensions and material.

Implementation of a Peltier-based cooling device for localized deep cortical deactivation during in vivo object recognition testing

NASA Astrophysics Data System (ADS)

Marra, Kyle; Graham, Brett; Carouso, Samantha; Cox, David

2012-02-01

While the application of local cortical cooling has recently become a focus of neurological research, extended localized deactivation deep within brain structures is still unexplored. Using a wirelessly controlled thermoelectric (Peltier) device and water-based heat sink, we have achieved inactivating temperatures (<20 C) at greater depths (>8 mm) than previously reported. After implanting the device into Long Evans rats' basolateral amygdala (BLA), an inhibitory brain center that controls anxiety and fear, we ran an open field test during which anxiety-driven behavioral tendencies were observed to decrease during cooling, thus confirming the device's effect on behavior. Our device will next be implanted in the rats' temporal association cortex (TeA) and recordings from our signal-tracing multichannel microelectrodes will measure and compare activated and deactivated neuronal activity so as to isolate and study the TeA signals responsible for object recognition. Having already achieved a top performing computational face-recognition system, the lab will utilize this TeA activity data to generalize its computational efforts of face recognition to achieve general object recognition.

A Highly Compliant Serpentine Shaped Polyimide Interconnect for Front-End Strain Relief in Chronic Neural Implants

PubMed Central

Sankar, Viswanath; Sanchez, Justin C.; McCumiskey, Edward; Brown, Nagid; Taylor, Curtis R.; Ehlert, Gregory J.; Sodano, Henry A.; Nishida, Toshikazu

2013-01-01

While the signal quality of recording neural electrodes is observed to degrade over time, the degradation mechanisms are complex and less easily observable. Recording microelectrodes failures are attributed to different biological factors such as tissue encapsulation, immune response, and disruption of blood-brain barrier (BBB) and non-biological factors such as strain due to micromotion, insulation delamination, corrosion, and surface roughness on the recording site (1–4). Strain due to brain micromotion is considered to be one of the important abiotic factors contributing to the failure of the neural implants. To reduce the forces exerted by the electrode on the brain, a high compliance 2D serpentine shaped electrode cable was designed, simulated, and measured using polyimide as the substrate material. Serpentine electrode cables were fabricated using MEMS microfabrication techniques, and the prototypes were subjected to load tests to experimentally measure the compliance. The compliance of the serpentine cable was numerically modeled and quantitatively measured to be up to 10 times higher than the compliance of a straight cable of same dimensions and material. PMID:24062716

Characterization and Application of a Chlorine Microelectrode for Measuring Monochloramine within a Biofilm

EPA Science Inventory

Chlorine microelectrodes with tip sizes of 5-15 μm were developed and used to measure biofilm monochloramine penetration profiles. The chlorine microelectrode showed response to total chlorine, including free chlorine, monochloramine, and dichloramine under various conditions. ...

An almost completely shielded microelectrode.

PubMed

Sachs, F; McGarrigle, R

1980-12-01

We present a new method of shielding microelectrodes to within 20 micron of the tip. Stray capacity is reduced to less than 50 fF. Ordinary microelectrodes are covered with silver in a vacuum evaporator. Silver is removed from the tip by contact with a ball of mercury. The microelectrode is then insulated with a glass barrel which is sealed by dipping the tip in diluted polystyrene in amyl acetate, or by dipping the electrode in melted wax. The latter method is quick, easy and reliable.

Neurosurgery and the dawning age of Brain-Machine Interfaces

PubMed Central

Rowland, Nathan C.; Breshears, Jonathan; Chang, Edward F.

2013-01-01

Brain–machine interfaces (BMIs) are on the horizon for clinical neurosurgery. Electrocorticography-based platforms are less invasive than implanted microelectrodes, however, the latter are unmatched in their ability to achieve fine motor control of a robotic prosthesis capable of natural human behaviors. These technologies will be crucial to restoring neural function to a large population of patients with severe neurologic impairment – including those with spinal cord injury, stroke, limb amputation, and disabling neuromuscular disorders such as amyotrophic lateral sclerosis. On the opposite end of the spectrum are neural enhancement technologies for specialized applications such as combat. An ongoing ethical dialogue is imminent as we prepare for BMI platforms to enter the neurosurgical realm of clinical management. PMID:23653884

Cell Patterning for Liver Tissue Engineering via Dielectrophoretic Mechanisms

PubMed Central

Yahya, Wan Nurlina Wan; Kadri, Nahrizul Adib; Ibrahim, Fatimah

2014-01-01

Liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a shortage of donors. Liver tissue engineering may offer an alternative by providing an implantable engineered liver. Currently, diverse types of engineering approaches for in vitro liver cell culture are available, including scaffold-based methods, microfluidic platforms, and micropatterning techniques. Active cell patterning via dielectrophoretic (DEP) force showed some advantages over other methods, including high speed, ease of handling, high precision and being label-free. This article summarizes liver function and regenerative mechanisms for better understanding in developing engineered liver. We then review recent advances in liver tissue engineering techniques and focus on DEP-based cell patterning, including microelectrode design and patterning configuration. PMID:24991941

Rapid evaluation of the durability of cortical neural implants using accelerated aging with reactive oxygen species

PubMed Central

Takmakov, Pavel; Ruda, Kiersten; Phillips, K Scott; Isayeva, Irada S; Krauthamer, Victor; Welle, Cristin G

2017-01-01

Objective A challenge for implementing high bandwidth cortical brain–machine interface devices in patients is the limited functional lifespan of implanted recording electrodes. Development of implant technology currently requires extensive non-clinical testing to demonstrate device performance. However, testing the durability of the implants in vivo is time-consuming and expensive. Validated in vitro methodologies may reduce the need for extensive testing in animal models. Approach Here we describe an in vitro platform for rapid evaluation of implant stability. We designed a reactive accelerated aging (RAA) protocol that employs elevated temperature and reactive oxygen species (ROS) to create a harsh aging environment. Commercially available microelectrode arrays (MEAs) were placed in a solution of hydrogen peroxide at 87 °C for a period of 7 days. We monitored changes to the implants with scanning electron microscopy and broad spectrum electrochemical impedance spectroscopy (1 Hz–1 MHz) and correlated the physical changes with impedance data to identify markers associated with implant failure. Main results RAA produced a diverse range of effects on the structural integrity and electrochemical properties of electrodes. Temperature and ROS appeared to have different effects on structural elements, with increased temperature causing insulation loss from the electrode microwires, and ROS concentration correlating with tungsten metal dissolution. All array types experienced impedance declines, consistent with published literature showing chronic (>30 days) declines in array impedance in vivo. Impedance change was greatest at frequencies <10 Hz, and smallest at frequencies 1 kHz and above. Though electrode performance is traditionally characterized by impedance at 1 kHz, our results indicate that an impedance change at 1 kHz is not a reliable predictive marker of implant degradation or failure. Significance ROS, which are known to be present in vivo, can create structural damage and change electrical properties of MEAs. Broad-spectrum electrical impedance spectroscopy demonstrates increased sensitivity to electrode damage compared with single-frequency measurements. RAA can be a useful tool to simulate worst-case in vivo damage resulting from chronic electrode implantation, simplifying the device development lifecycle. PMID:25627426

In Vivo Neural Recording and Electrochemical Performance of Microelectrode Arrays Modified by Rough-Surfaced AuPt Alloy Nanoparticles with Nanoporosity

PubMed Central

Zhao, Zongya; Gong, Ruxue; Zheng, Liang; Wang, Jue

2016-01-01

In order to reduce the impedance and improve in vivo neural recording performance of our developed Michigan type silicon electrodes, rough-surfaced AuPt alloy nanoparticles with nanoporosity were deposited on gold microelectrode sites through electro-co-deposition of Au-Pt-Cu alloy nanoparticles, followed by chemical dealloying Cu. The AuPt alloy nanoparticles modified gold microelectrode sites were characterized by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and in vivo neural recording experiment. The SEM images showed that the prepared AuPt alloy nanoparticles exhibited cauliflower-like shapes and possessed very rough surfaces with many different sizes of pores. Average impedance of rough-surfaced AuPt alloy nanoparticles modified sites was 0.23 MΩ at 1 kHz, which was only 4.7% of that of bare gold microelectrode sites (4.9 MΩ), and corresponding in vitro background noise in the range of 1 Hz to 7500 Hz decreased to 7.5 μVrms from 34.1 μVrms at bare gold microelectrode sites. Spontaneous spike signal recording was used to evaluate in vivo neural recording performance of modified microelectrode sites, and results showed that rough-surfaced AuPt alloy nanoparticles modified microelectrode sites exhibited higher average spike signal-to-noise ratio (SNR) of 4.8 in lateral globus pallidus (GPe) due to lower background noise compared to control microelectrodes. Electro-co-deposition of Au-Pt-Cu alloy nanoparticles combined with chemical dealloying Cu was a convenient way for increasing the effective surface area of microelectrode sites, which could reduce electrode impedance and improve the quality of in vivo spike signal recording. PMID:27827893

Composite wire microelectrode and method of making same

DOE Office of Scientific and Technical Information (OSTI.GOV)

Isaacs, H.S.; Aldykiewicz, A.J. Jr.

1996-12-03

A composite wire microelectrode for making electro-chemical measurements, and method of making same, are disclosed. The microelectrode includes an inner conductive sensing wire and an outer tube that is oxidized to form a dielectric, self-healing oxide layer around the sensing wire. 4 figs.

Properties of Retinal Precursor Cells Grown on Vertically Aligned Multiwalled Carbon Nanotubes Generated for the Modification of Retinal Implant-Embedded Microelectrode Arrays

PubMed Central

Johnen, Sandra; Meißner, Frank; Krug, Mario; Baltz, Thomas; Endler, Ingolf; Mokwa, Wilfried; Walter, Peter

2016-01-01

Background. To analyze the biocompatibility of vertically aligned multiwalled carbon nanotubes (MWCNT), used as nanomodification to optimize the properties of prostheses-embedded microelectrodes that induce electrical stimulation of surviving retinal cells. Methods. MWCNT were synthesized on silicon wafers. Their growth was achieved by iron particles (Fe) or mixtures of iron-platinum (Fe-Pt) and iron-titanium (Fe-Ti) acting as catalysts. Viability, growth, adhesion, and gene expression of L-929 and retinal precursor (R28) cells were analyzed after nondirect and direct contact. Results. Nondirect contact had almost no influence on cell growth, as measured in comparison to reference materials with defined levels of cytotoxicity. Both cell types exhibited good proliferation properties on each MWCNT-coated wafer. Viability ranged from 95.9 to 99.8%, in which better survival was observed for nonfunctionalized MWCNT generated with the Fe-Pt and Fe-Ti catalyst mixtures. R28 cells grown on the MWCNT-coated wafers showed a decreased gene expression associated with neural and glial properties. Expression of the cell cycle-related genes CCNC, MYC, and TP53 was slightly downregulated. Cultivation on plasma-treated MWCNT did not lead to additional changes. Conclusions. All tested MWCNT-covered slices showed good biocompatibility profiles, confirming that this nanotechnology is a promising tool to improve prostheses bearing electrodes which connect with retinal tissue. PMID:27200182

Properties of Retinal Precursor Cells Grown on Vertically Aligned Multiwalled Carbon Nanotubes Generated for the Modification of Retinal Implant-Embedded Microelectrode Arrays.

PubMed

Johnen, Sandra; Meißner, Frank; Krug, Mario; Baltz, Thomas; Endler, Ingolf; Mokwa, Wilfried; Walter, Peter

2016-01-01

Background. To analyze the biocompatibility of vertically aligned multiwalled carbon nanotubes (MWCNT), used as nanomodification to optimize the properties of prostheses-embedded microelectrodes that induce electrical stimulation of surviving retinal cells. Methods. MWCNT were synthesized on silicon wafers. Their growth was achieved by iron particles (Fe) or mixtures of iron-platinum (Fe-Pt) and iron-titanium (Fe-Ti) acting as catalysts. Viability, growth, adhesion, and gene expression of L-929 and retinal precursor (R28) cells were analyzed after nondirect and direct contact. Results. Nondirect contact had almost no influence on cell growth, as measured in comparison to reference materials with defined levels of cytotoxicity. Both cell types exhibited good proliferation properties on each MWCNT-coated wafer. Viability ranged from 95.9 to 99.8%, in which better survival was observed for nonfunctionalized MWCNT generated with the Fe-Pt and Fe-Ti catalyst mixtures. R28 cells grown on the MWCNT-coated wafers showed a decreased gene expression associated with neural and glial properties. Expression of the cell cycle-related genes CCNC, MYC, and TP53 was slightly downregulated. Cultivation on plasma-treated MWCNT did not lead to additional changes. Conclusions. All tested MWCNT-covered slices showed good biocompatibility profiles, confirming that this nanotechnology is a promising tool to improve prostheses bearing electrodes which connect with retinal tissue.

Cortical choline transporter function measured in vivo using choline-sensitive microelectrodes: clearance of endogenous and exogenous choline and effects of removal of cholinergic terminals.

PubMed

Parikh, V; Sarter, M

2006-04-01

The capacity of the high-affinity choline transporter (CHT) to import choline into presynaptic terminals is essential for acetylcholine synthesis. Ceramic-based microelectrodes, coated at recording sites with choline oxidase to detect extracellular choline concentration changes, were attached to multibarrel glass micropipettes and implanted into the rat frontoparietal cortex. Pressure ejections of hemicholinium-3 (HC-3), a selective CHT blocker, dose-dependently reduced the uptake rate of exogenous choline as well as that of choline generated in response to terminal depolarization. Following the removal of CHTs, choline signal recordings confirmed that the demonstration of potassium-induced choline signals and HC-3-induced decreases in choline clearance require the presence of cholinergic terminals. The results obtained from lesioned animals also confirmed the selectivity of the effects of HC-3 on choline clearance in intact animals. Residual cortical choline clearance correlated significantly with CHT-immunoreactivity in lesioned and intact animals. Finally, synaptosomal choline uptake assays were conducted under conditions reflecting in vivo basal extracellular choline concentrations. Results from these assays confirmed the capacity of CHTs measured in vivo and indicated that diffusion of substrate away from the electrode did not confound the in vivo findings. Collectively, these results indicate that increases in extracellular choline concentrations, irrespective of source, are rapidly cleared by CHTs.

A wideband wireless neural stimulation platform for high-density microelectrode arrays.

PubMed

Myers, Frank B; Simpson, Jim A; Ghovanloo, Maysam

2006-01-01

We describe a system that allows researchers to control an implantable neural microstimulator from a PC via a USB 2.0 interface and a novel dual-carrier wireless link, which provides separate data and power transmission. Our wireless stimulator, Interestim-2B (IS-2B), is a modular device capable of generating controlled-current stimulation pulse trains across 32 sites per module with support for a variety of stimulation schemes (biphasic/monophasic, bipolar/monopolar). We have developed software to generate multi-site stimulation commands for the IS-2B based on streaming data from artificial sensory devices such as cameras and microphones. For PC interfacing, we have developed a USB 2.0 microcontroller-based interface. Data is transmitted using frequency-shift keying (FSK) at 6/12 MHz to achieve a data rate of 3 Mb/s via a pair of rectangular coils. Power is generated using a class-E power amplifier operating at 1 MHz and transmitted via a separate pair of spiral planar coils which are oriented perpendicular to the data coils to minimize cross-coupling. We have successfully demonstrated the operation of the system by applying it as a visual prosthesis. Pulse-frequency modulated stimuli are generated in real-time based on a grayscale image from a webcam. These pulses are projected onto an 11x11 LED matrix that represents a 2D microelectrode array.

Validity of Single Tract Microelectrode Recording in Subthalamic Nucleus Stimulation

PubMed Central

Umemura, Atsushi; Oka, Yuichi; Yamada, Kazuo; Oyama, Genko; Shimo, Yasushi; Hattori, Nobutaka

2013-01-01

In surgery for subthalamic nucleus (STN) deep brain stimulation (DBS), precise implantation of the lead into the STN is essential. Physiological refinement with microelectrode recording (MER) is the gold standard for identifying STN. We studied single tract MER findings and surgical outcomes and verified our surgical method using single tract MER. The number of trajectories in MER and the final position of lead placement were retrospectively analyzed in 440 sides of STN DBS in 221 patients. Bilateral STN DBS yielded marked improvement in the motor score, dyskinesia/fluctuation score, and reduced requirement of dopaminergic medication in this series. The number of trajectories required to obtain sufficient activity of the STN was one in 79.0%, two in 18.2%, and three or more in 2.5% of 440 sides. In 92 sides requiring altered trajectory, the final direction of trajectory movement was posterior in 73.9%, anterior in 13.0%, lateral in 5.4%, and medial in 4.3%. In 18 patients, posterior moves were required due to significant brain shift with intracranial air caused by outflow of CSF during the second side procedure. Sufficient STN activity is obtained with minimum trajectories by proper targeting and precise interpretation of MER findings even in the single tract method. Anterior–posterior moves rather than medial–lateral moves should be attempted first in cases with insufficient recording of STN activity. PMID:24140767

Basal Ganglia Neuronal Activity during Scanning Eye Movements in Parkinson’s Disease

PubMed Central

Sieger, Tomáš; Bonnet, Cecilia; Serranová, Tereza; Wild, Jiří; Novák, Daniel; Růžička, Filip; Urgošík, Dušan; Růžička, Evžen; Gaymard, Bertrand; Jech, Robert

2013-01-01

The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsońs disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control. PMID:24223158

Magnetron sputtered diamond-like carbon microelectrodes for on-chip measurement of quantal catecholamine release from cells

PubMed Central

Gao, Yuanfang; Chen, Xiaohui; Gupta, Sanju; Gillis, Kevin D.; Gangopadhyay, Shubhra

2008-01-01

Carbon electrodes are widely used in electrochemistry due to their low cost, wide potential window, and low and stable background noise. Carbon-fiber electrodes (CFE) are commonly used to electrochemically measure “quantal” catecholamine release via exocytosis from individual cells, but it is difficult to integrate CFEs into lab-on-a-chip devices. Here we report the development of nitrogen doped diamond-like carbon (DLC:N) microelectrodes on a chip to monitor quantal release of catecholamines from cells. Advantages of DLC:N microelectrodes are that they are batch producible at low cost, and are harder and more durable than graphite films. The DLC:N microelectrodes were prepared by a magnetron sputtering process with nitrogen doping. The 30 μm by 40 μm DLC:N microelectrodes were patterned onto microscope glass slides by photolithography and lift-off technology. The properties of the DLC:N microelectrodes were characterized by AFM, Raman spectroscopy and cyclic voltammetry. Quantal catecholamine release was recorded amperometrically from bovine adrenal chromaffin cells on the DLC:N microelectrodes. Amperometric spikes due to quantal release of catecholamines were similar in amplitude and area as those recorded using CFEs and the background current and noise levels of microchip DLC:N electrodes were also comparable to CFEs. Therefore, DLC:N microelectrodes are suitable for microchip-based high-throughput measurement of quantal exocytosis with applications in basic research, drug discovery and cell-based biosensors. PMID:18493856

A MULTIPLEXED ASSAY FOR DETERMINATION OF NEUROTOXICANT EFFECTS ON SPONTANEOUS NETWORK ACTIVITY AND CELL VIABILITY FROM MICROELECTRODE ARRAYS

EPA Science Inventory

AbstractTITLE: A MULTIPLEXED ASSAY FOR DETERMINATION OF NEUROTOXICANT EFFECTS ON SPONTANEOUS NETWORK ACTIVITY AND CELL VIABILITY FROM MICROELECTRODE ARRAYSABSTRACT BODY: Microelectrode array (MEA) recordings are increasingly being used as an in vitro method to detect and characte...

Experiments on pumping of liquids using arrays of microelectrodes subjected to travelling wave potentials

NASA Astrophysics Data System (ADS)

García-Sánchez, P.; Ramos, A.; Green, Nicolas G.; Morgan, H.

2008-12-01

Net fluid flow of electrolytes driven on an array of microelectrodes subjected to a travelling-wave potential is presented. Two sizes of platinum microelectrodes have been studied. In both arrays, at low voltages the liquid flows according to the prediction given by ac electroosmotic theory. At voltages above a threshold the fluid flow is reversed. Measurements of the electrical current when the microelectrode array is pumping the liquid are also reported. Transient behaviours in both electrical current and fluid velocity have been observed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Cheng; Jacobs, Christopher B.; Nguyen, Michael

Microelectrodes modified with carbon nanotubes (CNTs) are useful for the detection of neurotransmitters because the CNTs enhance sensitivity and have electrocatalytic effects. CNTs can be grown on carbon fiber microelectrodes (CFMEs) but the intrinsic electrochemical activity of carbon fibers makes evaluating the effect of CNT enhancement difficult. Metal wires are highly conductive and many metals have no intrinsic electrochemical activity for dopamine, so we investigated CNTs grown on metal wires as microelectrodes for neurotransmitter detection. In this work, we successfully grew CNTs on niobium substrates for the first time. Instead of planar metal surfaces, metal wires with a diameter ofmore » only 25 μm were used as CNT substrates; these have potential in tissue applications due to their minimal tissue damage and high spatial resolution. Scanning electron microscopy shows that aligned CNTs are grown on metal wires after chemical vapor deposition. By use of fast-scan cyclic voltammetry, CNT-coated niobium (CNT-Nb) microelectrodes exhibit higher sensitivity and lower ΔE p value compared to CNTs grown on carbon fibers or other metal wires. The limit of detection for dopamine at CNT-Nb microelectrodes is 11 ± 1 nM, which is approximately 2-fold lower than that of bare CFMEs. Adsorption processes were modeled with a Langmuir isotherm, and detection of other neurochemicals was also characterized, including ascorbic acid, 3,4-dihydroxyphenylacetic acid, serotonin, adenosine, and histamine. CNT-Nb microelectrodes were used to monitor stimulated dopamine release in anesthetized rats with high sensitivity. This research demonstrates that CNT-grown metal microelectrodes, especially CNTs grown on Nb microelectrodes, are useful for monitoring neurotransmitters.« less

Equivalent Circuit of the Neuro-Electronic Junction for Signal Recordings From Planar and Engulfed Micro-Nano-Electrodes.

PubMed

Massobrio, Giuseppe; Martinoia, Sergio; Massobrio, Paolo

2018-02-01

In the latest years, several attempts to develop extracellular microtransducers to record electrophysiological activity of excitable cells have been done. In particular, many efforts have been oriented to increase the coupling conditions, and, thus, improving the quality of the recorded signal. Gold mushroom-shaped microelectrodes (GMμE) are an example of nano-devices to achieve those requirements. In this study, we developed an equivalent electrical circuit of the neuron-microelectrode system interface to simulate signal recordings from both planar and engulfed micro-nano-electrodes. To this purpose, models of the neuron, planar, gold planar microelectrode, and GMμE, neuro-electronic junction (microelectrode-electrolyte interface, cleft effect, and protein-glycocalyx electric double layer) are presented. Then, neuronal electrical activity is simulated by Hspice software, and analyzed as a function of the most sensitive biophysical models parameters, such as the neuron-microelectrode cleft width, spreading and seal resistances, ion-channel densities, double-layer properties, and microelectrode geometries. Results are referenced to the experimentally recorded electrophysiological neuronal signals reported in the literature.

A 100-Channel Hermetically Sealed Implantable Device for Chronic Wireless Neurosensing Applications

PubMed Central

Yin, Ming; Borton, David A.; Aceros, Juan; Patterson, William R.; Nurmikko, Arto V.

2014-01-01

A 100-channel fully implantable wireless broadband neural recording system was developed. It features 100 parallel broadband (0.1 Hz–7.8 kHz) neural recording channels, a medical grade 200 mAh Li-ion battery recharged inductively at 150 kHz, and data telemetry using 3.2 GHz to 3.8 GHz FSK modulated wireless link for 48 Mbps Manchester encoded data. All active electronics are hermetically sealed in a titanium enclosure with a sapphire window for electromagnetic transparency. A custom, high-density configuration of 100 individual hermetic feedthrough pins enable connection to an intracortical neural recording microelectrode array. A 100 MHz bandwidth custom receiver was built to remotely receive the FSK signal and achieved −77.7 dBm sensitivity with 10−8 BER at 48 Mbps data rate. ESD testing on all the electronic inputs and outputs has proven that the implantable device satisfies the HBM Class-1B ESD Standard. In addition, the evaluation of the worst-case charge density delivered to the tissue from each I/O pin verifies the patient safety of the device in the event of failure. Finally, the functionality and reliability of the complete device has been tested on-bench and further validated chronically in ongoing freely moving swine and monkey animal trials for more than one year to date. PMID:23853294

Influence of transmucosal height in abutments of single and multiple implant-supported prostheses: a non-linear three-dimensional finite element analysis.

PubMed

Borie, Eduardo; Leal, Eduardo; Orsi, Iara Augusta; Salamanca, Carlos; Dias, Fernando José; Weber, Benjamin

2018-01-01

The aim of this study was to analyze the influence of three different transmucosal heights of the abutments in single and multiple implant-supported prostheses through the finite element method. External hexagon implants, MicroUnit, and EsthetiCone abutments were scanned and placed in an edentulous maxillary model obtained from a tomography database. The simulations were divided into two groups: (1) one implant with 3.75 × 10 mm placed in the upper central incisor, simulating a single implant-supported fixed prosthesis with an EsthetiCone abutment; and (2) two implants with 3.75 × 10 mm placed in the upper lateral incisors with MicroUnit abutments, simulating a multiple implant-supported prosthesis. Subsequently, each group was subdivided into three models according to the transmucosal height (1, 2, and 3 mm). A static oblique load at an angle of 45 degrees to the long axis of the implant in palatal-buccal direction of 150 and 75 N was applied for multiple and single implant-supported prosthesis, respectively. The implants and abutments were assessed according to the equivalent Von Mises stress analyses while the bone and ceramics were analyzed through maximum and minimum principal stresses. The total deformation values increased in all models, while the transmucosal height was augmented. The transmucosal height of the abutments influences the stress values at the bone, ceramics, implants, and abutments of both the single and multiple implant-supported prostheses, with the transmucosal height of 1 mm showing the lowest stress values.

Unilateral hearing during development: hemispheric specificity in plastic reorganizations

PubMed Central

Kral, Andrej; Heid, Silvia; Hubka, Peter; Tillein, Jochen

2013-01-01

The present study investigates the hemispheric contributions of neuronal reorganization following early single-sided hearing (unilateral deafness). The experiments were performed on ten cats from our colony of deaf white cats. Two were identified in early hearing screening as unilaterally congenitally deaf. The remaining eight were bilaterally congenitally deaf, unilaterally implanted at different ages with a cochlear implant. Implanted animals were chronically stimulated using a single-channel portable signal processor for two to five months. Microelectrode recordings were performed at the primary auditory cortex under stimulation at the hearing and deaf ear with bilateral cochlear implants. Local field potentials (LFPs) were compared at the cortex ipsilateral and contralateral to the hearing ear. The focus of the study was on the morphology and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced hemisphere-specific effects were observed. Morphology of amplitude-normalized LFPs for stimulation of the deaf and the hearing ear was similar for responses recorded at the same hemisphere. However, when comparisons were performed between the hemispheres, the morphology was more dissimilar even though the same ear was stimulated. This demonstrates hemispheric specificity of some cortical adaptations irrespective of the ear stimulated. The results suggest a specific adaptation process at the hemisphere ipsilateral to the hearing ear, involving specific (down-regulated inhibitory) mechanisms not found in the contralateral hemisphere. Finally, onset latencies revealed that the sensitive period for the cortex ipsilateral to the hearing ear is shorter than that for the contralateral cortex. Unilateral hearing experience leads to a functionally-asymmetric brain with different neuronal reorganizations and different sensitive periods involved. PMID:24348345

Unilateral hearing during development: hemispheric specificity in plastic reorganizations.

PubMed

Kral, Andrej; Heid, Silvia; Hubka, Peter; Tillein, Jochen

2013-01-01

The present study investigates the hemispheric contributions of neuronal reorganization following early single-sided hearing (unilateral deafness). The experiments were performed on ten cats from our colony of deaf white cats. Two were identified in early hearing screening as unilaterally congenitally deaf. The remaining eight were bilaterally congenitally deaf, unilaterally implanted at different ages with a cochlear implant. Implanted animals were chronically stimulated using a single-channel portable signal processor for two to five months. Microelectrode recordings were performed at the primary auditory cortex under stimulation at the hearing and deaf ear with bilateral cochlear implants. Local field potentials (LFPs) were compared at the cortex ipsilateral and contralateral to the hearing ear. The focus of the study was on the morphology and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced hemisphere-specific effects were observed. Morphology of amplitude-normalized LFPs for stimulation of the deaf and the hearing ear was similar for responses recorded at the same hemisphere. However, when comparisons were performed between the hemispheres, the morphology was more dissimilar even though the same ear was stimulated. This demonstrates hemispheric specificity of some cortical adaptations irrespective of the ear stimulated. The results suggest a specific adaptation process at the hemisphere ipsilateral to the hearing ear, involving specific (down-regulated inhibitory) mechanisms not found in the contralateral hemisphere. Finally, onset latencies revealed that the sensitive period for the cortex ipsilateral to the hearing ear is shorter than that for the contralateral cortex. Unilateral hearing experience leads to a functionally-asymmetric brain with different neuronal reorganizations and different sensitive periods involved.

Utility of microelectrodes in high-pressure experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Golas, J.; Drickamer, H.G.; Faulkner, L.R.

1991-11-28

A method for preparing platinum cylindrical microelectrodes for applications in high-pressure measurements is described. Advantages of microelectrodes of this geometry are illustrated with voltammetric and chonoamperometric experiments performed at pressures of 1-8,000 bar. Quantitative data on the pressure dependence of diffusion coefficients of K[sub 3]Fe(CN)[sub 6] and O[sub 2] in 0.1 M KCl solutions are presented together with qualitative remarks on the behavior of these systems at higher pressure. The results for microelectrodes are compared to those obtained at large cylindrical Pt electrodes under the same experimental conditions.

Inherently aligned microfluidic electrodes composed of liquid metal.

PubMed

So, Ju-Hee; Dickey, Michael D

2011-03-07

This paper describes the fabrication and characterization of microelectrodes that are inherently aligned with microfluidic channels and in direct contact with the fluid in the channels. Injecting low melting point alloys, such as eutectic gallium indium (EGaIn), into microchannels at room temperature (or just above room temperature) offers a simple way to fabricate microelectrodes. The channels that define the shape and position of the microelectrodes are fabricated simultaneously with other microfluidic channels (i.e., those used to manipulate fluids) in a single step; consequently, all of the components are inherently aligned. In contrast, conventional techniques require multiple fabrication steps and registration (i.e., alignment of the electrodes with the microfluidic channels), which are technically challenging. The distinguishing characteristic of this work is that the electrodes are in direct contact with the fluid in the microfluidic channel, which is useful for a number of applications such as electrophoresis. Periodic posts between the microelectrodes and the microfluidic channel prevent the liquid metal from entering the microfluidic channel during injection. A thin oxide skin that forms rapidly and spontaneously on the surface of the metal stabilizes mechanically the otherwise low viscosity, high surface tension fluid within the channel. Moreover, the injected electrodes vertically span the sidewalls of the channel, which allows for the application of uniform electric field lines throughout the height of the channel and perpendicular to the direction of flow. The electrodes are mechanically stable over operating conditions commonly used in microfluidic applications; the mechanical stability depends on the magnitude of the applied bias, the nature of the bias (DC vs. AC), and the conductivity of the solutions in the microfluidic channel. Electrodes formed using alloys with melting points above room temperature ensure mechanical stability over all of the conditions explored. As a demonstration of their utility, the fluidic electrodes are used for electrohydrodynamic mixing, which requires extremely high electric fields (~10(5) V m(-1)).

Localized electron transfer rates and microelectrode-based enrichment of microbial communities within a phototrophic microbial mat.

PubMed

Babauta, Jerome T; Atci, Erhan; Ha, Phuc T; Lindemann, Stephen R; Ewing, Timothy; Call, Douglas R; Fredrickson, James K; Beyenal, Haluk

2014-01-01

Phototrophic microbial mats frequently exhibit sharp, light-dependent redox gradients that regulate microbial respiration on specific electron acceptors as a function of depth. In this work, a benthic phototrophic microbial mat from Hot Lake, a hypersaline, epsomitic lake located near Oroville in north-central Washington, was used to develop a microscale electrochemical method to study local electron transfer processes within the mat. To characterize the physicochemical variables influencing electron transfer, we initially quantified redox potential, pH, and dissolved oxygen gradients by depth in the mat under photic and aphotic conditions. We further demonstrated that power output of a mat fuel cell was light-dependent. To study local electron transfer processes, we deployed a microscale electrode (microelectrode) with tip size ~20 μm. To enrich a subset of microorganisms capable of interacting with the microelectrode, we anodically polarized the microelectrode at depth in the mat. Subsequently, to characterize the microelectrode-associated community and compare it to the neighboring mat community, we performed amplicon sequencing of the V1-V3 region of the 16S gene. Differences in Bray-Curtis beta diversity, illustrated by large changes in relative abundance at the phylum level, suggested successful enrichment of specific mat community members on the microelectrode surface. The microelectrode-associated community exhibited substantially reduced alpha diversity and elevated relative abundances of Prosthecochloris, Loktanella, Catellibacterium, other unclassified members of Rhodobacteraceae, Thiomicrospira, and Limnobacter, compared with the community at an equivalent depth in the mat. Our results suggest that local electron transfer to an anodically polarized microelectrode selected for a specific microbial population, with substantially more abundance and diversity of sulfur-oxidizing phylotypes compared with the neighboring mat community.

Localized electron transfer rates and microelectrode-based enrichment of microbial communities within a phototrophic microbial mat

PubMed Central

Babauta, Jerome T.; Atci, Erhan; Ha, Phuc T.; Lindemann, Stephen R.; Ewing, Timothy; Call, Douglas R.; Fredrickson, James K.; Beyenal, Haluk

2014-01-01

Phototrophic microbial mats frequently exhibit sharp, light-dependent redox gradients that regulate microbial respiration on specific electron acceptors as a function of depth. In this work, a benthic phototrophic microbial mat from Hot Lake, a hypersaline, epsomitic lake located near Oroville in north-central Washington, was used to develop a microscale electrochemical method to study local electron transfer processes within the mat. To characterize the physicochemical variables influencing electron transfer, we initially quantified redox potential, pH, and dissolved oxygen gradients by depth in the mat under photic and aphotic conditions. We further demonstrated that power output of a mat fuel cell was light-dependent. To study local electron transfer processes, we deployed a microscale electrode (microelectrode) with tip size ~20 μm. To enrich a subset of microorganisms capable of interacting with the microelectrode, we anodically polarized the microelectrode at depth in the mat. Subsequently, to characterize the microelectrode-associated community and compare it to the neighboring mat community, we performed amplicon sequencing of the V1–V3 region of the 16S gene. Differences in Bray-Curtis beta diversity, illustrated by large changes in relative abundance at the phylum level, suggested successful enrichment of specific mat community members on the microelectrode surface. The microelectrode-associated community exhibited substantially reduced alpha diversity and elevated relative abundances of Prosthecochloris, Loktanella, Catellibacterium, other unclassified members of Rhodobacteraceae, Thiomicrospira, and Limnobacter, compared with the community at an equivalent depth in the mat. Our results suggest that local electron transfer to an anodically polarized microelectrode selected for a specific microbial population, with substantially more abundance and diversity of sulfur-oxidizing phylotypes compared with the neighboring mat community. PMID:24478768

Localized electron transfer rates and microelectrode-based enrichment of microbial communities within a phototrophic microbial mat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Babauta, Jerome T.; Atci, Erhan; Ha, Phuc T.

2014-01-01

Phototrophic microbial mats frequently exhibit sharp, light-dependent redox gradients that regulate microbial respiration on specific electron acceptors as a function of depth. In this work, a benthic phototrophic microbial mat from Hot Lake, a hypersaline, epsomitic lake located near Oroville in north-central Washington, was used to develop a microscale electrochemical method to study local electron transfer processes within the mat. To characterize the physicochemical variables influencing electron transfer, we initially quantified redox potential, pH, and dissolved oxygen gradients by depth in the mat under photic and aphotic conditions. We further demonstrated that power output of a mat fuel cell wasmore » light-dependent. To study local electron transfer processes, we deployed a microscale electrode (microelectrode) with tip size ~20 μm. To enrich a subset of microorganisms capable of interacting with the microelectrode, we anodically polarized the microelectrode at depth in the mat. Subsequently, to characterize the microelectrode- associated community and compare it to the neighboring mat community, we performed amplicon sequencing of the V1-V3 region of the 16S gene. Differences in Bray-Curtis beta diversity, illustrated by large changes in relative abundance at the phylum level, suggested successful enrichment of specific mat community members on the microelectrode surface. The microelectrode-associated community exhibited substantially reduced alpha diversity and elevated relative abundances of Prosthecochloris, Loktanella, Catellibacterium, other unclassified members of Rhodobacteraceae, Thiomicrospira, and Limnobacter, compared with the community at an equivalent depth in the mat. Our results suggest that local electron transfer to an anodically polarized microelectrode selected for a specific microbial population, with substantially more abundance and diversity of sulfur-oxidizing phylotypes compared with the neighboring mat community.« less

Conducting polymer electrodes for visual prostheses.

PubMed

Green, R A; Devillaine, F; Dodds, C; Matteucci, P; Chen, S; Byrnes-Preston, P; Poole-Warren, L A; Lovell, N H; Suaning, G J

2010-01-01

Conducting polymers (CPs) have the potential to provide superior neural interfaces to conventional metal electrodes by introducing more efficient charge transfer across the same geometric area. In this study the conducting polymer poly(ethylene dioxythiophene) (PEDOT) was coated on platinum (Pt) microelectrode arrays. The in vitro electrical characteristics were assessed during biphasic stimulation regimes applied between electrode pairs. It was demonstrated that PEDOT could reduce the potential excursion at a Pt electrode interface by an order of magnitude. The charge injection limit of PEDOT was found to be 15 x larger than Pt. Additionally, PEDOT coated electrodes were acutely implanted in the suprachoroidal space of a cat retina. It was demonstrated that PEDOT coated electrodes also had lower potential excursions in vivo and electrically evoked potentials (EEPs) could be detected within the vision cortex.

Gold Nanoparticles for Neural Prosthetics Devices

PubMed Central

Zhang, Huanan; Shih, Jimmy; Zhu, Jian; Kotov, Nicholas A.

2012-01-01

Treatments of neurological diseases and the realization of brain-computer interfaces require ultrasmall electrodes which are “invisible” to resident immune cells. Functional electrodes smaller than 50μm are impossible to produce with traditional materials due to high interfacial impedance at the characteristic frequency of neural activity and insufficient charge storage capacity. The problem can be resolved by using gold nanoparticle nanocomposites. Careful comparison indicates that layer-by-layer assembled films from Au NPs provide more than threefold improvement in interfacial impedance and one order of magnitude increase in charge storage capacity. Prototypes of microelectrodes could be made using traditional photolithography. Integration of unique nanocomposite materials with microfabrication techniques opens the door for practical realization of the ultrasmall implantable electrodes. Further improvement of electrical properties is expected when using special shapes of gold nanoparticles. PMID:22734673

Integration of MnO2 thin film and carbon nanotubes to three-dimensional carbon microelectrodes for electrochemical microcapacitors

NASA Astrophysics Data System (ADS)

Jiang, Shulan; Shi, Tielin; Liu, Dan; Long, Hu; Xi, Shuang; Wu, Fengshun; Li, Xiaoping; Xia, Qi; Tang, Zirong

2014-09-01

Large-scale three-dimensional (3D) hybrid microelectrodes have been fabricated through modified carbon microelectromechanical systems (Carbon-MEMS) process and electrochemical deposition method. Greatly improved electrochemical performance has been shown for the 3D photoresist-derived carbon microelectrodes with the integration of carbon nanotubes (CNTs) and manganese dioxide (MnO2). The electrochemical measurements of the microelectrodes indicate that the specific geometric capacitance can reach up to 238 mF cm-2 at the current density of 0.5 mA cm-2. The capacitance loss is less than 18.2% of the original value after 6000 charge-discharge cycles. This study shows that stacking of MnO2 film and integrating of CNTs to the 3D glassy carbon microelectrodes have great potential for on-chip microcapacitors as energy storage devices, and the presented approach is promising for large-scale and low-cost manufacturing.

A three-dimensional microelectrode array composed of vertically aligned ultra-dense carbon nanotube networks

NASA Astrophysics Data System (ADS)

Nick, C.; Yadav, S.; Joshi, R.; Schneider, J. J.; Thielemann, C.

2015-07-01

Electrodes based on carbon nanotubes are a promising approach to manufacture highly sensitive sensors with a low limit of signal detection and a high signal-to-noise ratio. This is achieved by dramatically increasing the electrochemical active surface area without increasing the overall geometrical dimensions. Typically, carbon nanotube electrodes are nearly planar and composed of randomly distributed carbon nanotube networks having a limited surface gain for a specific geometrical surface area. To overcome this limitation, we have introduced vertically aligned carbon nanotube (VACNT) networks as electrodes, which are arranged in a microelectrode pattern of 60 single electrodes. Each microelectrode features a very high aspect ratio of more than 300 and thus a dramatically increased surface area. These microelectrodes composed of VACNT networks display dramatically decreased impedance over the entire frequency range compared to planar microelectrodes caused by the enormous capacity increase. This is experimentally verified by electrochemical impedance spectroscopy and cyclic voltammetry.

Screening metal nanoparticles using boron-doped diamond microelectrodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ivandini, Tribidasari A., E-mail: ivandini.tri@sci.ui.ac.id; Rangkuti, Prasmita K.; Einaga, Yasuaki

2016-04-19

Boron-doped diamond (BDD) microelectrodes were used to observe the correlation between electrocatalytic currents caused by individual Pt nanoparticle (Pt-np) collisions at the electrode. The BDD microelectrodes, ∼20 µm diameter and ∼2 µm particle size, were fabricated at the surface of tungsten wires. Pt-np with a size of 1 to 5 nm with agglomerations up to 20 nm was used for observation. The electrolytic currents were observed via catalytic reaction of 15 mM hydrazine in 50 mM phosphate buffer solution at Pt-np at 0.4 V when it collides with the surface of the microelectrodes. The low current noise and wider potential window in the measurements using BDD microelectrodemore » produced a better results, which represents a better correlation to the TEM result of the Pt-np, compared to when gold microelectrodes was used.« less

Sonochemically Fabricated Microelectrode Arrays for Use as Sensing Platforms

PubMed Central

Collyer, Stuart D.; Davis, Frank; Higson, Séamus P.J.

2010-01-01

The development, manufacture, modification and subsequent utilisation of sonochemically-formed microelectrode arrays is described for a range of applications. Initial fabrication of the sensing platform utilises ultrasonic ablation of electrochemically insulating polymers deposited upon conductive carbon substrates, forming an array of up to 70,000 microelectrode pores cm−2. Electrochemical and optical analyses using these arrays, their enhanced signal response and stir-independence area are all discussed. The growth of conducting polymeric “mushroom” protrusion arrays with entrapped biological entities, thereby forming biosensors is detailed. The simplicity and inexpensiveness of this approach, lending itself ideally to mass fabrication coupled with unrivalled sensitivity and stir independence makes commercial viability of this process a reality. Application of microelectrode arrays as functional components within sensors include devices for detection of chlorine, glucose, ethanol and pesticides. Immunosensors based on microelectrode arrays are described within this monograph for antigens associated with prostate cancer and transient ischemic attacks (strokes). PMID:22399926

Tapered microelectrode array system for dielectrophoretically filtration: fabrication, characterization, and simulation study

NASA Astrophysics Data System (ADS)

Buyong, Muhamad Ramdzan; Larki, Farhad; Takamura, Yuzuru; Majlis, Burhanuddin Yeop

2017-10-01

This paper presents the fabrication, characterization, and simulation of microelectrode arrays system with tapered profile having an aluminum surface for dielectrophoresis (DEP)-based manipulation of particles. The proposed structure demonstrates more effective electric field gradient compared with its counterpart with untapered profile. Therefore, according to the asymmetric distribution of the electric field in the active region of microelectrode, it produces more effective particle manipulation. The tapered aluminum microelectrode array (TAMA) fabrication process uses a state-of-the-art technique in the formation of the resist's taper profile. The performance of TAMA with various sidewall profile angles (5 deg to 90 deg) was analyzed through finite-element method numerical simulations to offer a better understanding of the origin of the sidewall profile effect. The ability of capturing and manipulating of the device was examined through modification of the Clausius-Mossotti factor and cross-over frequency (f). The fabricated system has been particularly implemented for filtration of particles with a desired diameter from a mixture of particles with three different diameters in an aqueous medium. The microelectrode system with tapered side wall profile offers a more efficient platform for particle manipulation and sensing applications compared with the conventional microelectrode systems.

Exercising Spatiotemporal Control of Cell Attachment with Optically Transparent Microelectrodes

PubMed Central

Shah, Sunny S.; Lee, Ji Youn; Verkhoturov, Stanislav; Tuleuova, Nazgul; Schweikert, Emile A.; Ramanculov, Erlan; Revzin, Alexander

2013-01-01

This paper describes a novel approach of controlling cell-surface interactions through an electrochemical “switching” of biointerfacial properties of optically transparent microelectrodes. The indium tin oxide (ITO) microelectrodes, fabricated on glass substrates, were modified with poly(ethylene glycol) (PEG) silane to make glass and ITO regions resistant to protein and cell adhesion. Cyclic voltammetry, with potassium ferricyanide serving as a redox reporter molecule, was used to monitor electron transfer across the electrolyte–ITO interface. PEG silane modification of ITO correlated with diminished electron transfer, judged by the disappearance of ferricyanide redox activity. Importantly, application of reductive potential (−1.4 V vs Ag/AgCl reference) corresponded with reappearance of typical ferricyanide redox peaks, thus pointing to desorption of an insulating PEG silane layer. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) characterization of the silanized ITO surfaces after electrical stimulation indicated complete removal of the silane layer. Significantly, electrical stimulation allowed to “switch” chosen electrodes from nonfouling to protein-adhesive while leaving other ITO and glass regions protected by a nonfouling PEG silane layer. The spatial and temporal control of biointerfacial properties afforded by our approach was utilized to micropattern proteins and cells and to construct micropatterned co-cultures. In the future, control of the biointerfacial properties afforded by this novel approach may allow the organization of multiple cell types into precise geometric configurations in order to create better in vitro mimics of cellular complexity of the native tissues. PMID:18512875

Vertically aligned carbon nanotube-sheathed carbon fibers as pristine microelectrodes for selective monitoring of ascorbate in vivo.

PubMed

Xiang, Ling; Yu, Ping; Hao, Jie; Zhang, Meining; Zhu, Lin; Dai, Liming; Mao, Lanqun

2014-04-15

Using as-synthesized vertically aligned carbon nanotube-sheathed carbon fibers (VACNT-CFs) as microelectrodes without any postsynthesis functionalization, we have developed in this study a new method for in vivo monitoring of ascorbate with high selectivity and reproducibility. The VACNT-CFs are formed via pyrolysis of iron phthalocyanine (FePc) on the carbon fiber support. After electrochemical pretreatment in 1.0 M NaOH solution, the pristine VACNT-CF microelectrodes exhibit typical microelectrode behavior with fast electron transfer kinetics for electrochemical oxidation of ascorbate and are useful for selective ascorbate monitoring even with other electroactive species (e.g., dopamine, uric acid, and 5-hydroxytryptamine) coexisting in rat brain. Pristine VACNT-CFs are further demonstrated to be a reliable and stable microelectrode for in vivo recording of the dynamic increase of ascorbate evoked by intracerebral infusion of glutamate. Use of a pristine VACNT-CF microelectrode can effectively avoid any manual electrode modification and is free from person-to-person and/or electrode-to-electrode deviations intrinsically associated with conventional CF electrode fabrication, which often involves electrode surface modification with randomly distributed CNTs or other pretreatments, and hence allows easy fabrication of highly selective, reproducible, and stable microelectrodes even by nonelectrochemists. Thus, this study offers a new and reliable platform for in vivo monitoring of neurochemicals (e.g., ascorbate) to largely facilitate future studies on the neurochemical processes involved in various physiological events.

Assessment of brain-machine interfaces from the perspective of people with paralysis

NASA Astrophysics Data System (ADS)

Blabe, Christine H.; Gilja, Vikash; Chestek, Cindy A.; Shenoy, Krishna V.; Anderson, Kim D.; Henderson, Jaimie M.

2015-08-01

Objective. One of the main goals of brain-machine interface (BMI) research is to restore function to people with paralysis. Currently, multiple BMI design features are being investigated, based on various input modalities (externally applied and surgically implantable sensors) and output modalities (e.g. control of computer systems, prosthetic arms, and functional electrical stimulation systems). While these technologies may eventually provide some level of benefit, they each carry associated burdens for end-users. We sought to assess the attitudes of people with paralysis toward using various technologies to achieve particular benefits, given the burdens currently associated with the use of each system. Approach. We designed and distributed a technology survey to determine the level of benefit necessary for people with tetraplegia due to spinal cord injury to consider using different technologies, given the burdens currently associated with them. The survey queried user preferences for 8 BMI technologies including electroencephalography, electrocorticography, and intracortical microelectrode arrays, as well as a commercially available eye tracking system for comparison. Participants used a 5-point scale to rate their likelihood to adopt these technologies for 13 potential control capabilities. Main Results. Survey respondents were most likely to adopt BMI technology to restore some of their natural upper extremity function, including restoration of hand grasp and/or some degree of natural arm movement. High speed typing and control of a fast robot arm were also of interest to this population. Surgically implanted wireless technologies were twice as ‘likely’ to be adopted as their wired equivalents. Significance. Assessing end-user preferences is an essential prerequisite to the design and implementation of any assistive technology. The results of this survey suggest that people with tetraplegia would adopt an unobtrusive, autonomous BMI system for both restoration of upper extremity function and control of external devices such as communication interfaces.

pHEMA Encapsulated PEDOT-PSS-CNT Microsphere Microelectrodes for Recording Single Unit Activity in the Brain

PubMed Central

Castagnola, Elisa; Maggiolini, Emma; Ceseracciu, Luca; Ciarpella, Francesca; Zucchini, Elena; De Faveri, Sara; Fadiga, Luciano; Ricci, Davide

2016-01-01

The long-term reliability of neural interfaces and stability of high-quality recordings are still unsolved issues in neuroscience research. High surface area PEDOT-PSS-CNT composites are able to greatly improve the performance of recording and stimulation for traditional intracortical metal microelectrodes by decreasing their impedance and increasing their charge transfer capability. This enhancement significantly reduces the size of the implantable device though preserving excellent electrical performances. On the other hand, the presence of nanomaterials often rises concerns regarding possible health hazards, especially when considering a clinical application of the devices. For this reason, we decided to explore the problem from a new perspective by designing and testing an innovative device based on nanostructured microspheres grown on a thin tether, integrating PEDOT-PSS-CNT nanocomposites with a soft synthetic permanent biocompatible hydrogel. The pHEMA hydrogel preserves the electrochemical performance and high quality recording ability of PEDOT-PSS-CNT coated devices, reduces the mechanical mismatch between soft brain tissue and stiff devices and also avoids direct contact between the neural tissue and the nanocomposite, by acting as a biocompatible protective barrier against potential nanomaterial detachment. Moreover, the spherical shape of the electrode together with the surface area increase provided by the nanocomposite deposited on it, maximize the electrical contact and may improve recording stability over time. These results have a good potential to contribute to fulfill the grand challenge of obtaining stable neural interfaces for long-term applications. PMID:27147944

A wire-based dual-analyte sensor for glucose and lactate: in vitro and in vivo evaluation.

PubMed

Ward, W Kenneth; House, Jody L; Birck, Jonathan; Anderson, Ellen M; Jansen, Lawrence B

2004-06-01

Continuous measurement of lactate is potentially useful for detecting physical exhaustion and for monitoring critical care conditions characterized by hypoperfusion, such as heart failure. In some conditions, it may be desirable to monitor more than one metabolic parameter concurrently. For this reason, we designed and fabricated twisted wire-based microelectrodes that can measure both lactate and glucose. These dual-analyte sensors were characterized in vitro by measuring their response to the analyte of interest and to assess whether they were susceptible to interference from the other analyte. When measured in stirred aqueous buffer, lactate sensors detected a very small amount of crosstalk from glucose in vitro, although this signal was less than 3% of the response to lactate. Glucose sensors did not detect crosstalk from lactate. Sensors were implanted subcutaneously in rats and tested during infusions of lactate and glucose. Each sensing electrode responded rapidly to changes in its analyte concentration, and there was no evidence of in vivo crosstalk. This study constitutes proof of the concept that oxidase-based, amperometric wire microsensors can detect changes in glucose and lactate during subcutaneous implantation in rats.

Fabrication of an inexpensive, implantable cooling device for reversible brain deactivation in animals ranging from rodents to primates

PubMed Central

Cooke, Dylan F.; Goldring, Adam B.; Yamayoshi, Itsukyo; Tsourkas, Phillippos; Recanzone, Gregg H.; Tiriac, Alex; Pan, Tingrui; Simon, Scott I.

2012-01-01

We have developed a compact and lightweight microfluidic cooling device to reversibly deactivate one or more areas of the neocortex to examine its functional macrocircuitry as well as behavioral and cortical plasticity. The device, which we term the “cooling chip,” consists of thin silicone tubing (through which chilled ethanol is circulated) embedded in mechanically compliant polydimethylsiloxane (PDMS). PDMS is tailored to compact device dimensions (as small as 21 mm3) that precisely accommodate the geometry of the targeted cortical area. The biocompatible design makes it suitable for both acute preparations and chronic implantation for long-term behavioral studies. The cooling chip accommodates an in-cortex microthermocouple measuring local cortical temperature. A microelectrode may be used to record simultaneous neural responses at the same location. Cortex temperature is controlled by computer regulation of the coolant flow, which can achieve a localized cortical temperature drop from 37 to 20°C in less than 3 min and maintain target temperature to within ±0.3°C indefinitely. Here we describe cooling chip fabrication and performance in mediating cessation of neural signaling in acute preparations of rodents, ferrets, and primates. PMID:22402651

Comparison of electrically evoked cortical potential thresholds generated with subretinal or suprachoroidal placement of a microelectrode array in the rabbit

NASA Astrophysics Data System (ADS)

Yamauchi, Yasuyuki; Franco, Luisa M.; Jackson, Douglas J.; Naber, John F.; Ofer Ziv, R.; Rizzo, Joseph F., III; Kaplan, Henry J.; Enzmann, Volker

2005-03-01

The aim of the study was to directly compare the threshold electrical charge density of the retina (retinal threshold) in rabbits for the generation of electrical evoked potentials (EEP) by delivering electrical stimulation with a custom-made microelectrode array (MEA) implanted into either the subretinal or suprachoroidal space. Nine eyes of seven Dutch-belted rabbits were studied. The electroretinogram (ERG), visual evoked potentials (VEP) and EEP were recorded. Electrodes for the VEP and EEP were placed on the dura mater overlying the visual cortex. The EEP was recorded following electrical stimulation of the MEA placed either subretinally beneath the visual streak of the retina or in the suprachoroidal space in the rabbit eye. An ab externo approach was used for placement of the MEA. Liquid perfluorodecaline (PFCL; 0.4 ml) was placed within the vitreous cavity to flatten the neurosensory retina on the MEA after subretinal implantation. The retinal threshold for generation of an EEP was determined for each MEA placement by three consecutive measurements consisting of 100 computer-averaged recordings. Animals were sacrificed at the conclusion of the experiment and the eyes were enucleated for histological examination. The retinal threshold to generate an EEP was 9 ± 7 nC (0.023 ± 0.016 mC cm-2) within the subretinal space and 150 ± 122 nC (0.375 ± 0.306 mC cm-2) within the suprachoroidal space. Histology showed disruption of the outer retina with subretinal but not suprachoroidal placement. The retinal threshold to elicit an EEP is significantly lower with subretinal placement of the MEA compared to suprachoroidal placement (P < 0.05). The retinal threshold charge density with a subretinal MEA is well below the published charge limit of 1 mC cm-2, which is the level below which chronic stimulation of the retina is considered necessary to avoid tissue damage (Shannon 1992 IEEE Trans. Biomed. Eng. 39 424-6). Supported in part by The Charles D Kelman, MD Postdoctoral Scholar Award 2003 (YY); Boston VA Hospital (V523P-7278); Research to Prevent Blindness, New York City, NY and Kentucky Research Challenge Trust Fund (HJK).

Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease.

PubMed

Brodsky, Matthew A; Anderson, Shannon; Murchison, Charles; Seier, Mara; Wilhelm, Jennifer; Vederman, Aaron; Burchiel, Kim J

2017-11-07

To compare motor and nonmotor outcomes at 6 months of asleep deep brain stimulation (DBS) for Parkinson disease (PD) using intraoperative imaging guidance to confirm electrode placement vs awake DBS using microelectrode recording to confirm electrode placement. DBS candidates with PD referred to Oregon Health & Science University underwent asleep DBS with imaging guidance. Six-month outcomes were compared to those of patients who previously underwent awake DBS by the same surgeon and center. Assessments included an "off"-levodopa Unified Parkinson's Disease Rating Scale (UPDRS) II and III, the 39-item Parkinson's Disease Questionnaire, motor diaries, and speech fluency. Thirty participants underwent asleep DBS and 39 underwent awake DBS. No difference was observed in improvement of UPDRS III (+14.8 ± 8.9 vs +17.6 ± 12.3 points, p = 0.19) or UPDRS II (+9.3 ± 2.7 vs +7.4 ± 5.8 points, p = 0.16). Improvement in "on" time without dyskinesia was superior in asleep DBS (+6.4 ± 3.0 h/d vs +1.7 ± 1.2 h/d, p = 0.002). Quality of life scores improved in both groups (+18.8 ± 9.4 in awake, +8.9 ± 11.5 in asleep). Improvement in summary index ( p = 0.004) and subscores for cognition ( p = 0.011) and communication ( p < 0.001) were superior in asleep DBS. Speech outcomes were superior in asleep DBS, both in category (+2.77 ± 4.3 points vs -6.31 ± 9.7 points ( p = 0.0012) and phonemic fluency (+1.0 ± 8.2 points vs -5.5 ± 9.6 points, p = 0.038). Asleep DBS for PD improved motor outcomes over 6 months on par with or better than awake DBS, was superior with regard to speech fluency and quality of life, and should be an option considered for all patients who are candidates for this treatment. NCT01703598. This study provides Class III evidence that for patients with PD undergoing DBS, asleep intraoperative CT imaging-guided implantation is not significantly different from awake microelectrode recording-guided implantation in improving motor outcomes at 6 months. © 2017 American Academy of Neurology.

A nanoporous alumina microelectrode array for functional cell-chip coupling.

PubMed

Wesche, Manuel; Hüske, Martin; Yakushenko, Alexey; Brüggemann, Dorothea; Mayer, Dirk; Offenhäusser, Andreas; Wolfrum, Bernhard

2012-12-14

The design of electrode interfaces has a strong impact on cell-based bioelectronic applications. We present a new type of microelectrode array chip featuring a nanoporous alumina interface. The chip is fabricated in a combination of top-down and bottom-up processes using state-of-the-art clean room technology and self-assembled generation of nanopores by aluminum anodization. The electrode characteristics are investigated in phosphate buffered saline as well as under cell culture conditions. We show that the modified microelectrodes exhibit decreased impedance compared to planar microelectrodes, which is caused by a nanostructuring effect of the underlying gold during anodization. The stability and biocompatibility of the device are demonstrated by measuring action potentials from cardiomyocyte-like cells growing on top of the chip. Cross sections of the cell-surface interface reveal that the cell membrane seals the nanoporous alumina layer without bending into the sub-50 nm apertures. The nanoporous microelectrode array device may be used as a platform for combining extracellular recording of cell activity with stimulating topographical cues.

Quasi-simultaneous Measurements of Ionic Currents by Vibrating Probe and pH Distribution by Ion-selective Microelectrode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Isaacs, H.S.; Lamaka, S.V.; Taryba, M.

2011-01-01

This work reports a new methodology to measure quasi-simultaneously the local electric fields and the distribution of specific ions in a solution via selective microelectrodes. The field produced by the net electric current was detected using the scanning vibrating electrode technique (SVET) with quasi-simultaneous measurements of pH with an ion-selective microelectrode (pH-SME). The measurements were performed in a validation cell providing a 48 ?m diameter Pt wire cross section as a source of electric current. A time lag between acquiring each current density and pH data-point was 1.5 s due to the response time of pH-SME. The quasi-simultaneous SVET-pH measurementsmore » that correlate electrochemical oxidation-reduction processes with acid-base chemical equilibria are reported for the first time. No cross-talk between the vibrating microelectrode and the ion-selective microelectrode could be detected under given experimental conditions.« less

A three-layer PMMA electrophoresis microchip with Pt microelectrodes insulated by a thin film for contactless conductivity detection.

PubMed

Liu, Junshan; Wang, Junyao; Chen, Zuanguang; Yu, Yong; Yang, Xiujuan; Zhang, Xianbin; Xu, Zheng; Liu, Chong

2011-03-07

A three-layer poly (methyl methacrylate) (PMMA) electrophoresis microchip integrated with Pt microelectrodes for contactless conductivity detection is presented. A 50 μm-thick PMMA film is used as the insulating layer and placed between the channel plate (containing the microchannel) and the electrode plate (containing the microelectrode). The three-layer structure facilitates the achievement of a thin insulating layer, obviates the difficulty of integrating microelectrodes on a thin film, and does not compromise the integration of microchips. To overcome the thermal and chemical incompatibilities of polymers and photolithographic techniques, a modified lift-off process was developed to integrate Pt microelectrodes onto the PMMA substrate. A novel two-step bonding method was created to assemble the complete PMMA microchip. A low limit of detection of 1.25 μg ml(-1) for Na(+) and high separation efficiency of 77,000 and 48,000 plates/m for Na(+) and K(+) were obtained when operating the detector at a low excitation frequency of 60 kHz.

Construction and electrochemical characterization of microelectrodes for improved sensitivity in paper-based analytical devices

PubMed Central

Santhiago, Murilo; Wydallis, John B.; Kubota, Lauro T.; Henry, Charles S.

2013-01-01

This work presents a simple, low cost method for creating microelectrodes for electrochemical paper-based analytical devices (ePADs). The microelectrodes were constructed by backfilling small holes made in polyester sheets using a CO2 laser etching system. To make electrical connections, the working electrodes were combined with silver screen-printed paper in a sandwich type two-electrode configuration. The devices were characterized using linear sweep voltammetry and the results are in good agreement with theoretical predictions for electrode size and shape. As a proof-of-concept, cysteine was measured using cobalt phthalocyanine as a redox mediator. The rate constant (kobs) for the chemical reaction between cysteine and the redox mediator was obtained by chronoamperometry and found to be on the order of 105 s−1 M−1. Using a microelectrode array, it was possible to reach a limit of detection of 4.8 μM for cysteine. The results show that carbon paste microelectrodes can be easily integrated with paper-based analytical devices. PMID:23581428

Construction and electrochemical characterization of microelectrodes for improved sensitivity in paper-based analytical devices.

PubMed

Santhiago, Murilo; Wydallis, John B; Kubota, Lauro T; Henry, Charles S

2013-05-21

This work presents a simple, low cost method for creating microelectrodes for electrochemical paper-based analytical devices (ePADs). The microelectrodes were constructed by backfilling small holes made in polyester sheets using a CO2 laser etching system. To make electrical connections, the working electrodes were combined with silver screen-printed paper in a sandwich type two-electrode configuration. The devices were characterized using linear sweep voltammetry, and the results are in good agreement with theoretical predictions for electrode size and shape. As a proof-of-concept, cysteine was measured using cobalt phthalocyanine as a redox mediator. The rate constant (k(obs)) for the chemical reaction between cysteine and the redox mediator was obtained by chronoamperometry and found to be on the order of 10(5) s(-1) M(-1). Using a microelectrode array, it was possible to reach a limit of detection of 4.8 μM for cysteine. The results show that carbon paste microelectrodes can be easily integrated with paper-based analytical devices.

Piezoelectric translator. A simple and inexpensive device to move microelectrodes and micropipettes small distances rapidly.

PubMed

Lederer, W J

1983-09-01

A device is described that is capable of rapidly moving microelectrodes and micropipettes over distances up to 15 mu. This piezoelectric transLator uses the diaphragm from virtually any available piezoelectric buzzer in combination with simple physical support and drive electronics. All of the necessary details for the construction of this small device are presented. Each finished unit is about 2 cm long with a diameter of 2 cm and can be readily adapted to existing manipulators. The translator has been found useful in aiding the independent penetration by one or more microelectrodes of single cells or of more complicated multicellular preparations (including those that lie behind a connective tissue layer). This new device offers fine control of microelectrode motion that cannot be obtained by the other methods used to aid microelectrode and micropipette penetration of cell membranes (e.g. capacitance overcompensation--"ringing in"' or "tickling"--or tapping the manipulator base). Finally, the device described in this paper is extremely simple and inexpensive to build.

Glassy carbon MEMS for novel origami-styled 3D integrated intracortical and epicortical neural probes

NASA Astrophysics Data System (ADS)

Goshi, Noah; Castagnola, Elisa; Vomero, Maria; Gueli, Calogero; Cea, Claudia; Zucchini, Elena; Bjanes, David; Maggiolini, Emma; Moritz, Chet; Kassegne, Sam; Ricci, Davide; Fadiga, Luciano

2018-06-01

We report on a novel technology for microfabricating 3D origami-styled micro electro-mechanical systems (MEMS) structures with glassy carbon (GC) features and a supporting polymer substrate. GC MEMS devices that open to form 3D microstructures are microfabricated from GC patterns that are made through pyrolysis of polymer precursors on high-temperature resisting substrates like silicon or quartz and then transferring the patterned devices to a flexible substrate like polyimide followed by deposition of an insulation layer. The devices on flexible substrate are then folded into 3D form in an origami-fashion. These 3D MEMS devices have tunable mechanical properties that are achieved by selectively varying the thickness of the polymeric substrate and insulation layers at any desired location. This technology opens new possibilities by enabling microfabrication of a variety of 3D GC MEMS structures suited to applications ranging from biochemical sensing to implantable microelectrode arrays. As a demonstration of the technology, a neural signal recording microelectrode array platform that integrates both surface (cortical) and depth (intracortical) GC microelectrodes onto a single flexible thin-film device is introduced. When the device is unfurled, a pre-shaped shank of polyimide automatically comes off the substrate and forms the penetrating part of the device in a 3D fashion. With the advantage of being highly reproducible and batch-fabricated, the device introduced here allows for simultaneous recording of electrophysiological signals from both the brain surface (electrocorticography—ECoG) and depth (single neuron). Our device, therefore, has the potential to elucidate the roles of underlying neurons on the different components of µECoG signals. For in vivo validation of the design capabilities, the recording sites are coated with a poly(3,4-ethylenedioxythiophene)—polystyrene sulfonate—carbon nanotube composite, to improve the electrical conductivity of the electrodes and consequently the quality of the recorded signals. Results show that both µECoG and intracortical arrays were able to acquire neural signals with high-sensitivity that increased with depth, thereby verifying the device functionality.

Chitosan coated carbon fiber microelectrode for selective in vivo detection of neurotransmitters in live zebrafish embryos

PubMed Central

Özel, Rıfat Emrah; Wallace, Kenneth N.; Andreescu, Silvana

2011-01-01

We report the development of a chitosan modified carbon fiber microelectrode for in vivo detection of serotonin. We find that chitosan has the ability to reject physiological levels of ascorbic acid interferences and facilitate selective and sensitive detection of in vivo levels of serotonin, a common catecholamine neurotransmitter. Presence of chitosan on the microelectrode surface was investigated using scanning electron microscopy (SEM) and cyclic voltammetry (CV). The electrode was characterized using differential pulse voltammetry (DPV). A detection limit of 1.6 nM serotonin with a sensitivity of 5.12 nA/µM, a linear range from 2 to 100 nM and a reproducibility of 6.5 % for n=6 electrodes were obtained. Chitosan modified microelectrodes selectively measure serotonin in presence of physiological levels of ascorbic acid. In vivo measurements were performed to measure concentration of serotonin in the live embryonic zebrafish intestine. The sensor quantifies in vivo intestinal levels of serotonin while successfully rejecting ascorbic acid interferences. We demonstrate that chitosan can be used as an effective coating to reject ascorbic acid interferences at carbon fiber microelectrodes, as an alternative to Nafion, and that chitosan modified microelectrodes are reliable tools for in vivo monitoring of changes in neurotransmitter levels. PMID:21601035

Nanoscale laminin coating modulates cortical scarring response around implanted silicon microelectrode arrays

NASA Astrophysics Data System (ADS)

He, Wei; McConnell, George C.; Bellamkonda, Ravi V.

2006-12-01

Neural electrodes could significantly enhance the quality of life for patients with sensory and/or motor deficits as well as improve our understanding of brain functions. However, long-term electrical connectivity between neural tissue and recording sites is compromised by the development of astroglial scar around the recording probes. In this study we investigate the effect of a nanoscale laminin (LN) coating on Si-based neural probes on chronic cortical tissue reaction in a rat model. Tissue reaction was evaluated after 1 day, 1 week, and 4 weeks post-implant for coated and uncoated probes using immunohistochemical techniques to evaluate activated microglia/macrophages (ED-1), astrocytes (GFAP) and neurons (NeuN). The coating did not have an observable effect on neuronal density or proximity to the electrode surface. However, the response of microglia/macrophages and astrocytes was altered by the coating. One day post-implant, we observed an ~60% increase in ED-1 expression near LN-coated probe sites compared with control uncoated probe sites. Four weeks post-implant, we observed an ~20% reduction in ED-1 expression along with an ~50% reduction in GFAP expression at coated relative to uncoated probe sites. These results suggest that LN has a stimulatory effect on early microglia activation, accelerating the phagocytic function of these cells. This hypothesis is further supported by the increased mRNA expression of several pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) in cultured microglia on LN-bound Si substrates. LN immunostaining of coated probes immediately after insertion and retrieval demonstrates that the coating integrity is not compromised by the shear force during insertion. We speculate, based on these encouraging results, that LN coating of Si neural probes could potentially improve chronic neural recordings through dispersion of the astroglial scar.

Scanning Electrochemical Microscopy as a Novel Proximity Sensor for Atraumatic Cochlear Implant Insertion

PubMed Central

Velmurugan, J.; Mirkin, M. V.; Svirsky, M. A.; Lalwani, A. K.; Llinas, R. R.

2014-01-01

A growing number of minimally invasive surgical and diagnostic procedures require the insertion of an optical, mechanical, or electronic device in narrow spaces inside a human body. In such procedures, precise motion control is essential to avoid damage to the patient’s tissues and/or the device itself. A typical example is the insertion of a cochlear implant which should ideally be done with minimum physical contact between the moving device and the cochlear canal walls or the basilar membrane. Because optical monitoring is not possible, alternative techniques for sub millimeter-scale distance control can be very useful for such procedures. The first requirement for distance control is distance sensing. We developed a novel approach to distance sensing based on the principles of scanning electrochemical microscopy (SECM). The SECM signal, i.e., the diffusion current to a microelectrode, is very sensitive to the distance between the probe surface and any electrically insulating object present in its proximity. With several amperometric microprobes fabricated on the surface of an insertable device, one can monitor the distances between different parts of the moving implant and the surrounding tissues. Unlike typical SECM experiments, in which a disk-shaped tip approaches a relatively smooth sample, complex geometries of the mobile device and its surroundings make distance sensing challenging. Additional issues include the possibility of electrode surface contamination in biological fluids and the requirement for a biologically compatible redox mediator. PMID:24845292

An implantable wireless neural interface for recording cortical circuit dynamics in moving primates

NASA Astrophysics Data System (ADS)

Borton, David A.; Yin, Ming; Aceros, Juan; Nurmikko, Arto

2013-04-01

Objective. Neural interface technology suitable for clinical translation has the potential to significantly impact the lives of amputees, spinal cord injury victims and those living with severe neuromotor disease. Such systems must be chronically safe, durable and effective. Approach. We have designed and implemented a neural interface microsystem, housed in a compact, subcutaneous and hermetically sealed titanium enclosure. The implanted device interfaces the brain with a 510k-approved, 100-element silicon-based microelectrode array via a custom hermetic feedthrough design. Full spectrum neural signals were amplified (0.1 Hz to 7.8 kHz, 200× gain) and multiplexed by a custom application specific integrated circuit, digitized and then packaged for transmission. The neural data (24 Mbps) were transmitted by a wireless data link carried on a frequency-shift-key-modulated signal at 3.2 and 3.8 GHz to a receiver 1 m away by design as a point-to-point communication link for human clinical use. The system was powered by an embedded medical grade rechargeable Li-ion battery for 7 h continuous operation between recharge via an inductive transcutaneous wireless power link at 2 MHz. Main results. Device verification and early validation were performed in both swine and non-human primate freely-moving animal models and showed that the wireless implant was electrically stable, effective in capturing and delivering broadband neural data, and safe for over one year of testing. In addition, we have used the multichannel data from these mobile animal models to demonstrate the ability to decode neural population dynamics associated with motor activity. Significance. We have developed an implanted wireless broadband neural recording device evaluated in non-human primate and swine. The use of this new implantable neural interface technology can provide insight into how to advance human neuroprostheses beyond the present early clinical trials. Further, such tools enable mobile patient use, have the potential for wider diagnosis of neurological conditions and will advance brain research.

Microfluidic Actuation of Carbon Nanotube Fibers for Neural Recordings

NASA Astrophysics Data System (ADS)

Vercosa, Daniel G.

Implantable devices to record and stimulate neural circuits have led to breakthroughs in neuroscience; however, technologies capable of electrical recording at the cellular level typically rely on rigid metals that poorly match the mechanical properties of soft brain tissue. As a result these electrodes often cause extensive acute and chronic injury, leading to short electrode lifetime. Recently, flexible electrodes such as Carbon Nanotube fibers (CNTf) have emerged as an attractive alternative to conventional electrodes and studies have shown that these flexible electrodes reduce neuro-inflammation and increase the quality and longevity of neural recordings. Insertion of these new compliant electrodes, however, remains challenge. The stiffening agents necessary to make the electrodes rigid enough to be inserted increases device footprint, which exacerbates brain damage during implantation. To overcome this challenge we have developed a novel technology to precisely implant and actuate high-performance, flexible carbon nanotube fiber (CNTf) microelectrodes without using a stiffening agents or shuttles. Instead, our technology uses drag forces within a microfluidic device to drive electrodes into tissue while minimizing the amount of fluid that is ejected into the tissue. In vitro experiments in brain phantoms, show that microfluidic actuated CNTf can be implanted at least 4.5 mm depth with 30 microm precision, while keeping the total volume of fluid ejected below 0.1 microL. As proof of concept, we inserted CNTfs in the small cnidarian Hydra littoralis and observed compound action potentials corresponding to contractions and in agreement with the literature. Additionally, brain slices extracted from transgenic mice were used to show that our device can be used to record spontaneous and light evoked activity from the cortex and deep brain regions such as the thalamic reticular nucleus (TRN). Overall our microfluidic actuation technology provides a platform for implanting and actuating flexible electrodes that significantly reduces damage during insertion.

Controlling the Electrochemically Active Area of Carbon Fiber Microelectrodes by the Electrodeposition and Selective Removal of an Insulating Photoresist

PubMed Central

Lambie, Bradley A.; Orwar, Owe; Weber, Stephen G.

2008-01-01

A new and simple method permits control of the electrochemically active area of a carbon fiber microelectrode. An electrophoretic photoresist insulates the 10 μm diameter carbon fiber microelectrodes. Photolysis of the photoresist followed by immersion of the exposed area into a developing solution reveals electroactive carbon fiber surface. The electroactive surface area exposed can be controlled with a good degree of reproducibility. PMID:16841943

Simultaneous mixing and pumping using asymmetric microelectrodes

NASA Astrophysics Data System (ADS)

Kim, Byoung Jae; Yoon, Sang Youl; Sung, Hyung Jin; Smith, Charles G.

2007-10-01

This study proposes ideas for simultaneous mixing and pumping using asymmetric microelectrode arrays. The driving force of the mixing and pumping was based on electroosmotic flows induced by alternating current (ac) electric fields on asymmetric microelectrodes. The key idea was to bend/incline the microelectrodes like diagonal/herringbone shapes. Four patterns of the asymmetric electrode arrays were considered depending on the shape of electrode arrays. For the diagonal shape, repeated and staggered patterns of the electrode arrays were studied. For the herringbone shape, diverging and converging patterns were examined. These microelectrode patterns forced fluid flows in the lateral direction leading to mixing and in the channel direction leading to pumping. Three-dimensional numerical simulations were carried out using the linear theories of ac electro-osmosis. The performances of the mixing and pumping were assessed in terms of the mixing efficiency and the pumping flow rate. The results indicated that the helical flow motions induced by the electrode arrays play a significant role in the mixing enhancement. The pumping performance was influenced by the slip velocity at the center region of the channel compared to that near the side walls.

Interdigitated Array microelectrode-based electrochemical impedance immunosensor for detection of Escherichia coli O157:H7.

PubMed

Yang, Liju; Li, Yanbin; Erf, Gisela F

2004-02-15

A label-free electrochemical impedance immunosensor for rapid detection of Escherichia coli O157:H7 was developed by immobilizing anti-E. coli antibodies onto an indium-tin oxide interdigitated array (IDA) microelectrode. Based on the general electronic equivalent model of an electrochemical cell and the behavior of the IDA microelectrode, an equivalent circuit, consisting of an ohmic resistor of the electrolyte between two electrodes and a double layer capacitor, an electron-transfer resistor, and a Warburg impedance around each electrode, was introduced for interpretation of the impedance components of the IDA microelectrode system. The results showed that the immobilization of antibodies and the binding of E. coli cells to the IDA microelectrode surface increased the electron-transfer resistance, which was directly measured with electrochemical impedance spectroscopy in the presence of [Fe(CN)(6)](3-/4-) as a redox probe. The electron-transfer resistance was correlated with the concentration of E. coli cells in a range from 4.36 x 10(5) to 4.36 x 10(8) cfu/mL with the detection limit of 10(6) cfu/mL.

Progress towards biocompatible intracortical microelectrodes for neural interfacing applications

NASA Astrophysics Data System (ADS)

Jorfi, Mehdi; Skousen, John L.; Weder, Christoph; Capadona, Jeffrey R.

2015-02-01

To ensure long-term consistent neural recordings, next-generation intracortical microelectrodes are being developed with an increased emphasis on reducing the neuro-inflammatory response. The increased emphasis stems from the improved understanding of the multifaceted role that inflammation may play in disrupting both biologic and abiologic components of the overall neural interface circuit. To combat neuro-inflammation and improve recording quality, the field is actively progressing from traditional inorganic materials towards approaches that either minimizes the microelectrode footprint or that incorporate compliant materials, bioactive molecules, conducting polymers or nanomaterials. However, the immune-privileged cortical tissue introduces an added complexity compared to other biomedical applications that remains to be fully understood. This review provides a comprehensive reflection on the current understanding of the key failure modes that may impact intracortical microelectrode performance. In addition, a detailed overview of the current status of various materials-based approaches that have gained interest for neural interfacing applications is presented, and key challenges that remain to be overcome are discussed. Finally, we present our vision on the future directions of materials-based treatments to improve intracortical microelectrodes for neural interfacing.

Progress Towards Biocompatible Intracortical Microelectrodes for Neural Interfacing Applications

PubMed Central

Jorfi, Mehdi; Skousen, John L.; Weder, Christoph; Capadona, Jeffrey R.

2015-01-01

To ensure long-term consistent neural recordings, next-generation intracortical microelectrodes are being developed with an increased emphasis on reducing the neuro-inflammatory response. The increased emphasis stems from the improved understanding of the multifaceted role that inflammation may play in disrupting both biologic and abiologic components of the overall neural interface circuit. To combat neuro-inflammation and improve recording quality, the field is actively progressing from traditional inorganic materials towards approaches that either minimizes the microelectrode footprint or that incorporate compliant materials, bioactive molecules, conducting polymers or nanomaterials. However, the immune-privileged cortical tissue introduces an added complexity compared to other biomedical applications that remains to be fully understood. This review provides a comprehensive reflection on the current understanding of the key failure modes that may impact intracortical microelectrode performance. In addition, a detailed overview of the current status of various materials-based approaches that have gained interest for neural interfacing applications is presented, and key challenges that remain to be overcome are discussed. Finally, we present our vision on the future directions of materials-based treatments to improve intracortical microelectrodes for neural interfacing. PMID:25460808

On-Line Monitoring the Growth of E. coli or HeLa Cells Using an Annular Microelectrode Piezoelectric Biosensor.

PubMed

Tong, Feifei; Lian, Yan; Han, Junliang

2016-12-18

Biological information is obtained from the interaction between the series detection electrode and the organism or the physical field of biological cultures in the non-mass responsive piezoelectric biosensor. Therefore, electric parameter of the electrode will affect the biosensor signal. The electric field distribution of the microelectrode used in this study was simulated using the COMSOL Multiphysics analytical tool. This process showed that the electric field spatial distribution is affected by the width of the electrode finger or the space between the electrodes. In addition, the characteristic response of the piezoelectric sensor constructed serially with an annular microelectrode was tested and applied for the continuous detection of Escherichia coli culture or HeLa cell culture. Results indicated that the piezoelectric biosensor with an annular microelectrode meets the requirements for the real-time detection of E. coli or HeLa cells in culture. Moreover, this kind of piezoelectric biosensor is more sensitive than the sensor with an interdigital microelectrode. Thus, the piezoelectric biosensor acts as an effective analysis tool for acquiring online cell or microbial culture information.

Evaluating the diffusion coefficient of dopamine at the cell surface during amperometric detection: disk vs ring microelectrodes.

PubMed

Trouillon, Raphaël; Lin, Yuqing; Mellander, Lisa J; Keighron, Jacqueline D; Ewing, Andrew G

2013-07-02

During exocytosis, small quantities of neurotransmitters are released by the cell. These neurotransmitters can be detected quantitatively using electrochemical methods, principally with disk carbon fiber microelectrode amperometry. An exocytotic event then results in the recording of a current peak whose characteristic features are directly related to the mechanisms of exocytosis. We have compared two exocytotic peak populations obtained from PC12 cells with a disk carbon fiber microelectrode and with a pyrolyzed carbon ring microelectrode array, with a 500 nm ring thickness. The specific shape of the ring electrode allows for precise analysis of diffusion processes at the vicinity of the cell membrane. Peaks obtained with a ring microelectrode array show a distorted average shape, owing to increased diffusion pathways. This result has been used to evaluate the diffusion coefficient of dopamine at the surface of a cell, which is up to an order of magnitude smaller than that measured in free buffer. The lower rate of diffusion is discussed as resulting from interactions with the glycocalyx.

Influence of geometry on the electrochemical response of carbon interdigitated microelectrodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kostecki, R.; Song, X.Y.; Kinoshita, K.

2000-05-01

Microelectrodes were fabricated by carbonizing photoresist (700--1,000 C) that was patterned on a Si wafer by use of a mask and UV photolithography. Two geometric designs of interdigitated carbon microelectrodes were produced with dimensions of about 500 {micro}m length and 50 {micro}m width. The carbon structures were characterized by Raman spectroscopy, atomic force microscopy, and optical microscopy. The electrochemical response of the microelectrodes was investigated by cyclic voltammetry using the I{sub 3}{sup {minus}}/I{sup {minus}} redox couple. The collection efficiencies of carbon inderdigitated array electrodes (IDAEs) varied from 59 to 90% depending on the cell size, geometry, and generator-collector arrangement. Thesemore » collection efficiencies are comparable to those reported with multiband (n > 25 bands) IDAEs.« less

A thermal-sensitive device fabricated with diamond film and a planar microelectrode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Changzhi Gu; Zengsun Jin; Xianyi Lu

1995-12-31

Polycrystalline diamond film were deposited by means of the hot filament CVD technique (HFCVD) onto a planar interdigital Ti microelectrode arrays, and forming a thermal-sensitive device, The resistor changes of diamond film caused by temperature are shown to be sensitive, reproducible, rapid and stable thermal-sensitive device. The characteristics of thermal-sensitive for this device was study. Functionalized diamond film deposited onto planar microelectrode arrays can easily detect temperature from 20{degrees}C to 700{degrees}C.

An image-processing strategy to extract important information suitable for a low-size stimulus pattern in a retinal prosthesis.

PubMed

Chen, Yili; Fu, Jixiang; Chu, Dawei; Li, Rongmao; Xie, Yaoqin

2017-11-27

A retinal prosthesis is designed to help the blind to obtain some sight. It consists of an external part and an internal part. The external part is made up of a camera, an image processor and an RF transmitter. The internal part is made up of an RF receiver, implant chip and microelectrode. Currently, the number of microelectrodes is in the hundreds, and we do not know the mechanism for using an electrode to stimulate the optic nerve. A simple hypothesis is that the pixels in an image correspond to the electrode. The images captured by the camera should be processed by suitable strategies to correspond to stimulation from the electrode. Thus, it is a question of how to obtain the important information from the image captured in the picture. Here, we use the region of interest (ROI), a useful algorithm for extracting the ROI, to retain the important information, and to remove the redundant information. This paper explains the details of the principles and functions of the ROI. Because we are investigating a real-time system, we need a fast processing ROI as a useful algorithm to extract the ROI. Thus, we simplified the ROI algorithm and used it in an outside image-processing digital signal processing (DSP) system of the retinal prosthesis. The results show that our image-processing strategies are suitable for a real-time retinal prosthesis and can eliminate redundant information and provide useful information for expression in a low-size image.

Real-time separation of multineuron recordings with a DSP32C signal processor.

PubMed

Gädicke, R; Albus, K

1995-04-01

We have developed a hardware and software package for real-time discrimination of multiple-unit activities recorded simultaneously from multiple microelectrodes using a VME-Bus system. Compared with other systems cited in literature or commercially available, our system has the following advantages. (1) Each electrode is served by its own preprocessor (DSP32C); (2) On-line spike discrimination is performed independently for each electrode. (3) The VME-bus allows processing of data received from 16 electrodes. The digitized (62.5 kHz) spike form is itself used as the model spike; the algorithm allows for comparing and sorting complete wave forms in real time into 8 different models per electrode.

Comparison of learning preferences of Turkish children who had been applied cochlear implantation in Turkey and Germany according to theory of multiple intelligence.

PubMed

Sahli, Sanem; Laszig, Roland; Aschendorff, Antje; Kroeger, Stefanie; Wesarg, Thomas; Belgin, Erol

2011-12-01

The aim of the study is to determinate the using dominant multiple intelligence types and compare the learning preferences of Turkish cochlear implanted children aged four to ten in Turkey and Germany according to Theory of multiple intelligence. The study has been conducted on a total of 80 children and four groups in Freiburg/Germany and Ankara/Turkey. The applications have been done in University of Freiburg, Cochlear Implant Center in Germany, and University of Hacettepe, ENT Department, Audiology and Speech Pathology Section in Turkey. In this study, the data have been collected by means of General Information Form and Cochlear Implant Information Form applied to parents. To determine the dominant multiple intelligence types of children, the TIMI (Teele Inventory of Multiple Intelligences) which was developed by Sue Teele have been used. The study results exposed that there was not a statistically significant difference on dominant intelligence areas and averages of scores of multiple intelligence types in control groups (p>0.05). Although, the dominant intelligence areas were different (except for first dominant intelligence) in cochlear implanted children in Turkey and Germany, there was not a statistically significant difference on averages of scores of dominant multiple intelligence types. Every hearing impaired child who started training, should be evaluated in terms of multiple intelligence areas and identified strengths and weaknesses. Multiple intelligence activities should be used in their educational programs. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Epoxy-encapsulated ceramic superconductor microelectrodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gollmor, R.O.; McDevitt, J.T.; Murray, R.W.

1989-12-01

A procedure is outlined for fabricating well-behaved microelectrodes from ceramic pellets of YBa{sub 2}CU{sub 3}O{sub 7} and Bi{sub 2}Sr{sub 2}CaCu{sub 2}O{sub 8} which involves systematic polishing of an epoxy-encapsulated superconductror chip, under Et{sub 4}NCIO{sub 4}/acetonitrile solution, to a potentiometric end point. Voltammetry of the resulting microelectrodes in acetronitrile is illustrated and compared to that arising from alternative superconductor electrode geometries. The microelectrodes have active electrode surface areas ranging from 2 {times} 10 {sup {minus} sup 6} to 3 {times} 10 {sup {minus} sup 4}cm{sup 2}, as characterized electrochemically and microscopically. The results discussed herein are steps toward developing the methodologymore » necessary to study the electrochemical response of high temperature superconductor phases at temperatures below theirtheir superconductor critical temperature.« less

Micromachined electrical cauterizer

DOEpatents

Lee, Abraham P.; Krulevitch, Peter A.; Northrup, M. Allen

1999-01-01

A micromachined electrical cauterizer. Microstructures are combined with microelectrodes for highly localized electro cauterization. Using boron etch stops and surface micromachining, microneedles with very smooth surfaces are made. Micromachining also allows for precision placement of electrodes by photolithography with micron sized gaps to allow for concentrated electric fields. A microcauterizer is fabricated by bulk etching silicon to form knife edges, then parallelly placed microelectrodes with gaps as small as 5 .mu.m are patterned and aligned adjacent the knife edges to provide homeostasis while cutting tissue. While most of the microelectrode lines are electrically insulated from the atmosphere by depositing and patterning silicon dioxide on the electric feedthrough portions, a window is opened in the silicon dioxide to expose the parallel microelectrode portion. This helps reduce power loss and assist in focusing the power locally for more efficient and safer procedures.

Micromachined electrical cauterizer

DOEpatents

Lee, A.P.; Krulevitch, P.A.; Northrup, M.A.

1999-08-31

A micromachined electrical cauterizer is disclosed. Microstructures are combined with microelectrodes for highly localized electro cauterization. Using boron etch stops and surface micromachining, microneedles with very smooth surfaces are made. Micromachining also allows for precision placement of electrodes by photolithography with micron sized gaps to allow for concentrated electric fields. A microcauterizer is fabricated by bulk etching silicon to form knife edges, then parallelly placed microelectrodes with gaps as small as 5 {mu}m are patterned and aligned adjacent the knife edges to provide homeostasis while cutting tissue. While most of the microelectrode lines are electrically insulated from the atmosphere by depositing and patterning silicon dioxide on the electric feedthrough portions, a window is opened in the silicon dioxide to expose the parallel microelectrode portion. This helps reduce power loss and assist in focusing the power locally for more efficient and safer procedures. 7 figs.

Determination of Sediment Oxygen Demand in the Ziya River Watershed, China: Based on Laboratory Core Incubation and Microelectrode Measurements

PubMed Central

Rong, Nan; Shan, Baoqing; Wang, Chao

2016-01-01

A study coupling sedimentcore incubation and microelectrode measurementwas performed to explore the sediment oxygen demand (SOD) at 16 stations in the Ziya River Watershed, a severely polluted and anoxic river system in the north of China. Total oxygen flux values in the range 0.19–1.41 g/(m2·d) with an average of 0.62 g/(m2·d) were obtained by core incubations, and diffusive oxygen flux values in the range 0.15–1.38 g/(m2·d) with an average of 0.51 g/(m2·d) were determined by microelectrodes. Total oxygen flux obviously correlated with diffusive oxygen flux (R2 = 0.842). The microelectrode method produced smaller results than the incubation method in 15 of 16 sites, and the diffusive oxygen flux was smaller than the total oxygen flux. Although the two sets of SOD values had significant difference accepted by the two methods via the Wilcoxon signed-rank test (p < 0.05), the microelectrode method was shown to produce results that were similar to those from the core incubation method. The microelectrode method, therefore, could be used as an alternative method for traditional core incubation method, or as a method to verify SOD rates measured by other methods. We consider that high potential sediment oxygen demand would occur in the Ziya River Watershed when the dissolved oxygen (DO) recovered in the overlying water. PMID:26907307

Evaluating the in vivo glial response to miniaturized parylene cortical probes coated with an ultra-fast degrading polymer to aid insertion

NASA Astrophysics Data System (ADS)

Lo, Meng-chen; Wang, Shuwu; Singh, Sagar; Damodaran, Vinod B.; Ahmed, Ijaz; Coffey, Kevin; Barker, David; Saste, Kshitij; Kals, Karanvir; Kaplan, Hilton M.; Kohn, Joachim; Shreiber, David I.; Zahn, Jeffrey D.

2018-06-01

Objective. Despite the feasibility of short-term neural recordings using implantable microelectrodes, attaining reliable, chronic recordings remains a challenge. Most neural recording devices suffer from a long-term tissue response, including gliosis, at the device–tissue interface. It was hypothesized that smaller, more flexible intracortical probes would limit gliosis by providing a better mechanical match with surrounding tissue. Approach. This paper describes the in vivo evaluation of flexible parylene microprobes designed to improve the interface with the adjacent neural tissue to limit gliosis and thereby allow for improved recording longevity. The probes were coated with an ultrafast degrading tyrosine-derived polycarbonate (E5005(2K)) polymer that provides temporary mechanical support for device implantation, yet degrades within 2 h post-implantation. A parametric study of probes of varying dimensions and polymer coating thicknesses were implanted in rat brains. The glial tissue response and neuronal loss were assessed from 72 h to 24 weeks post-implantation via immunohistochemistry. Main results. Experimental results suggest that both probe and polymer coating sizes affect the extent of gliosis. When an appropriate sized coating dimension (100 µm  ×  100 µm) and small probe (30 µm  ×  5 µm) was implanted, a minimal post-implantation glial response was observed. No discernible gliosis was detected when compared to tissue where a sham control consisting of a solid degradable polymer shuttle of the same dimensions was inserted. A larger polymer coating (200 µm  ×  200 µm) device induced a more severe glial response at later time points, suggesting that the initial insertion trauma can affect gliosis even when the polymer shuttle degrades rapidly. A larger degree of gliosis was also observed when comparing a larger sized probe (80 µm  ×  5 µm) to a smaller probe (30 µm  ×  5 µm) using the same polymer coating size (100 µm  ×  100 µm). There was no significant neuronal loss around the implantation sites for most device candidates except the group with largest polymer coating and probe sizes. Significance. These results suggest that: (1) the degree of mechanical trauma at device implantation and mechanical mismatches at the probe-tissue interface affect long term gliosis; (2) smaller, more flexible probes may minimize the glial response to provide improved tissue biocompatibility when used for chronic neural signal recording; and (3) some degree of glial scarring did not significantly affect neuronal distribution around the probe.

OptoZIF Drive: a 3D printed implant and assembly tool package for neural recording and optical stimulation in freely moving mice

NASA Astrophysics Data System (ADS)

Freedman, David S.; Schroeder, Joseph B.; Telian, Gregory I.; Zhang, Zhengyang; Sunil, Smrithi; Ritt, Jason T.

2016-12-01

Objective. Behavioral neuroscience studies in freely moving rodents require small, light-weight implants to facilitate neural recording and stimulation. Our goal was to develop an integrated package of 3D printed parts and assembly aids for labs to rapidly fabricate, with minimal training, an implant that combines individually positionable microelectrodes, an optical fiber, zero insertion force (ZIF-clip) headstage connection, and secondary recording electrodes, e.g. for electromyography (EMG). Approach. Starting from previous implant designs that position recording electrodes using a control screw, we developed an implant where the main drive body, protective shell, and non-metal components of the microdrives are 3D printed in parallel. We compared alternative shapes and orientations of circuit boards for electrode connection to the headstage, in terms of their size, weight, and ease of wire insertion. We iteratively refined assembly methods, and integrated additional assembly aids into the 3D printed casing. Main results. We demonstrate the effectiveness of the OptoZIF Drive by performing real time optogenetic feedback in behaving mice. A novel feature of the OptoZIF Drive is its vertical circuit board, which facilities direct ZIF-clip connection. This feature requires angled insertion of an optical fiber that still can exit the drive from the center of a ring of recording electrodes. We designed an innovative 2-part protective shell that can be installed during the implant surgery to facilitate making additional connections to the circuit board. We use this feature to show that facial EMG in mice can be used as a control signal to lock stimulation to the animal’s motion, with stable EMG signal over several months. To decrease assembly time, reduce assembly errors, and improve repeatability, we fabricate assembly aids including a drive holder, a drill guide, an implant fixture for microelectode ‘pinning’, and a gold plating fixture. Significance. The expanding capability of optogenetic tools motivates continuing development of small optoelectric devices for stimulation and recording in freely moving mice. The OptoZIF Drive is the first to natively support ZIF-clip connection to recording hardware, which further supports a decrease in implant cross-section. The integrated 3D printed package of drive components and assembly tools facilities implant construction. The easy interfacing and installation of auxiliary electrodes makes the OptoZIF Drive especially attractive for real time feedback stimulation experiments.

Evaluating the in vivo glial response to miniaturized parylene cortical probes coated with an ultra-fast degrading polymer to aid insertion.

PubMed

Lo, Meng-Chen; Wang, Shuwu; Singh, Sagar; Damodaran, Vinod B; Ahmed, Ijaz; Coffey, Kevin; Barker, David; Saste, Kshitij; Kals, Karanvir; Kaplan, Hilton M; Kohn, Joachim; Shreiber, David I; Zahn, Jeffrey D

2018-06-01

Despite the feasibility of short-term neural recordings using implantable microelectrodes, attaining reliable, chronic recordings remains a challenge. Most neural recording devices suffer from a long-term tissue response, including gliosis, at the device-tissue interface. It was hypothesized that smaller, more flexible intracortical probes would limit gliosis by providing a better mechanical match with surrounding tissue. This paper describes the in vivo evaluation of flexible parylene microprobes designed to improve the interface with the adjacent neural tissue to limit gliosis and thereby allow for improved recording longevity. The probes were coated with an ultrafast degrading tyrosine-derived polycarbonate (E5005(2K)) polymer that provides temporary mechanical support for device implantation, yet degrades within 2 h post-implantation. A parametric study of probes of varying dimensions and polymer coating thicknesses were implanted in rat brains. The glial tissue response and neuronal loss were assessed from 72 h to 24 weeks post-implantation via immunohistochemistry. Experimental results suggest that both probe and polymer coating sizes affect the extent of gliosis. When an appropriate sized coating dimension (100 µm  ×  100 µm) and small probe (30 µm  ×  5 µm) was implanted, a minimal post-implantation glial response was observed. No discernible gliosis was detected when compared to tissue where a sham control consisting of a solid degradable polymer shuttle of the same dimensions was inserted. A larger polymer coating (200 µm  ×  200 µm) device induced a more severe glial response at later time points, suggesting that the initial insertion trauma can affect gliosis even when the polymer shuttle degrades rapidly. A larger degree of gliosis was also observed when comparing a larger sized probe (80 µm  ×  5 µm) to a smaller probe (30 µm  ×  5 µm) using the same polymer coating size (100 µm  ×  100 µm). There was no significant neuronal loss around the implantation sites for most device candidates except the group with largest polymer coating and probe sizes. These results suggest that: (1) the degree of mechanical trauma at device implantation and mechanical mismatches at the probe-tissue interface affect long term gliosis; (2) smaller, more flexible probes may minimize the glial response to provide improved tissue biocompatibility when used for chronic neural signal recording; and (3) some degree of glial scarring did not significantly affect neuronal distribution around the probe.

Instant loading with intraoral welding technique and PRAMA implants: a new prosthetic approach.

PubMed

Celletti, R; Fanali, S; Laici, C U; Santori, C; Pignatelli, P; Sinjari, B

2017-01-01

When splinting multiple implants passive fit of the framework should be achieved to avoid excessive force distribution on the implants. Recently, a protocol was suggested for immediate loading of multiple implants by welding a titanium bar to implant abutments directly in the oral cavity so as to create a customized, precise and passive metal-reinforced provisional restoration. The intraoral welding technique subsequently proves to be a successful option in the full-arch immediate restorations of the mandible and maxilla. The aim of this article is to present a case report in which a new prosthetic approach, using trans-mucosal implants, is described. Dental implants are instantly loaded with a provisional prosthesis supported by an intraoral welded titanium framework to obtain a precise passive fit of the immediate loaded prosthesis.

Curing the Epilepsies: The Promise of Research

MedlinePlus

... Using microelectrodes, researchers are able to better characterize high-frequency oscillations (HFOs). Abnormal HFOs have been linked to ... Using microelectrodes, researchers are able to better characterize high-frequency oscillations. Top Develop New Animal Models for Studying ...

An inexpensive frequency-modulated (FM) audio monitor of time-dependent analog parameters.

PubMed

Langdon, R B; Jacobs, R S

1980-02-01

The standard method for quantification and presentation of an experimental variable in real time is the use of visual display on the ordinate of an oscilloscope screen or chart recorder. This paper describes a relatively simple electronic circuit, using commercially available and inexpensive integrated circuits (IC), which generates an audible tone, the pitch of which varies in proportion to a running variable of interest. This device, which we call an "Audioscope," can accept as input the monitor output from any instrument that expresses an experimental parameter as a dc voltage. The Audioscope is particularly useful in implanting microelectrodes intracellularly. It may also function to mediate the first step in data recording on magnetic tape, and/or data analysis and reduction by electronic circuitary. We estimate that this device can be built, with two-channel capability, for less than $50, and in less than 10 hr by an experienced electronics technician.

Mapping brain activity with flexible graphene micro-transistors

NASA Astrophysics Data System (ADS)

Blaschke, Benno M.; Tort-Colet, Núria; Guimerà-Brunet, Anton; Weinert, Julia; Rousseau, Lionel; Heimann, Axel; Drieschner, Simon; Kempski, Oliver; Villa, Rosa; Sanchez-Vives, Maria V.; Garrido, Jose A.

2017-06-01

Establishing a reliable communication interface between the brain and electronic devices is of paramount importance for exploiting the full potential of neural prostheses. Current microelectrode technologies for recording electrical activity, however, evidence important shortcomings, e.g. challenging high density integration. Solution-gated field-effect transistors (SGFETs), on the other hand, could overcome these shortcomings if a suitable transistor material were available. Graphene is particularly attractive due to its biocompatibility, chemical stability, flexibility, low intrinsic electronic noise and high charge carrier mobilities. Here, we report on the use of an array of flexible graphene SGFETs for recording spontaneous slow waves, as well as visually evoked and also pre-epileptic activity in vivo in rats. The flexible array of graphene SGFETs allows mapping brain electrical activity with excellent signal-to-noise ratio (SNR), suggesting that this technology could lay the foundation for a future generation of in vivo recording implants.

Optima HD Imax: Molecular Implant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tieger, D. R.; Splinter, P. R.; Hsieh, T. J.

2008-11-03

Molecular implantation offers semiconductor device manufacturers multiple advantages over traditional high current ion implanters. The dose multiplication due to implanting more than one atom per molecule and the transport of beams at higher energies relative to the effective particle energies result in significant throughput enhancements without risk of energy contamination. The Optima HD Imax is introduced with molecular implant capability and the ability to reach up to 4.2 keV effective {sup 11}B from octadecaborane (B{sub 18}H{sub 22}). The ion source and beamline are optimized for molecular species ionization and transport. The beamline is coupled to the Optima HD mechanically scannedmore » endstation. The use of spot beam technology with ionized molecules maximizes the throughput potential and produces uniform implants with fast setup time and with superior angle control. The implanter architecture is designed to run multiple molecular species; for example, in addition to B{sub 18}H{sub 22} the system is capable of implanting carbon molecules for strain engineering and shallow junction engineering. Source lifetime data and typical operating conditions are described both for high dose, memory applications such as dual poly gate as well as lower energy implants for source drain extension and contact implants. Throughputs have been achieved in excess of 50 wafers per hour at doses up to 1x10{sup 16} ions/cm{sup 2} and for energies as low as 1 keV.« less

Integration of thermocouple microelectrode in the scanning electrochemical microscope at variable temperatures: simultaneous temperature and electrochemical imaging and its kinetic studies.

PubMed

Pan, He; Zhang, Hailing; Lai, Junhui; Gu, Xiaoxin; Sun, Jianjun; Tang, Jing; Jin, Tao

2017-03-24

We describe herein a method for the simultaneous measurement of temperature and electrochemical signal with a new type of thermocouple microelectrode. The thermocouple microelectrode can be used not only as a thermometer but also as a scanning electrochemical microscope (SECM) tip in the reaction between tip-generated bromine and a heated Cu sample. The influence of temperature on the SECM imaging process and the related kinetic parameters have been studied, such as kinetic constant and activation energy.

Integration of thermocouple microelectrode in the scanning electrochemical microscope at variable temperatures: simultaneous temperature and electrochemical imaging and its kinetic studies

PubMed Central

Pan, He; Zhang, Hailing; Lai, Junhui; Gu, Xiaoxin; Sun, Jianjun; Tang, Jing; Jin, Tao

2017-01-01

We describe herein a method for the simultaneous measurement of temperature and electrochemical signal with a new type of thermocouple microelectrode. The thermocouple microelectrode can be used not only as a thermometer but also as a scanning electrochemical microscope (SECM) tip in the reaction between tip-generated bromine and a heated Cu sample. The influence of temperature on the SECM imaging process and the related kinetic parameters have been studied, such as kinetic constant and activation energy. PMID:28338002

Spatially selective formation of hydrocarbon, fluorocarbon, and hydroxyl-terminated monolayers on a microelectrode array.

PubMed

Cook, Kevin M; Nissley, Daniel A; Ferguson, Gregory S

2013-06-11

A protection-deprotection strategy, using gold oxide as a passivating layer, was used to direct the self-assembly of monolayers (SAMs) selectively at individual gold microelectrodes in an array. This approach allowed the formation of hydroxyl-terminated monolayers, without side reactions, in addition to hydrocarbon and fluorocarbon SAMs. Fluorescence microscopy was used to visualize selective dewetting of hydrophobic monolayers by an aqueous dye solution, and spatially resolved X-ray photoelectron spectroscopy was used to demonstrate a lack of cross-contamination on neighboring microelectrodes in the array.

Concept and Development of an Electronic Framework Intended for Electrode and Surrounding Environment Characterization In Vivo

PubMed Central

Rieger, Stefan B.; Pfau, Jennifer; Stieglitz, Thomas; Asplund, Maria; Ordonez, Juan S.

2016-01-01

There has been substantial progress over the last decade towards miniaturizing implantable microelectrodes for use in Active Implantable Medical Devices (AIMD). Compared to the rapid development and complexity of electrode miniaturization, methods to monitor and assess functional integrity and electrical functionality of these electrodes, particularly during long term stimulation, have not progressed to the same extent. Evaluation methods that form the gold standard, such as stimulus pulse testing, cyclic voltammetry and electrochemical impedance spectroscopy, are either still bound to laboratory infrastructure (impractical for long term in vivo experiments) or deliver no comprehensive insight into the material’s behaviour. As there is a lack of cost effective and practical predictive measures to understand long term electrode behaviour in vivo, material investigations need to be performed after explantation of the electrodes. We propose the analysis of the electrode and its environment in situ, to better understand and correlate the effects leading to electrode failure. The derived knowledge shall eventually lead to improved electrode designs, increased electrode functionality and safety in clinical applications. In this paper, the concept, design and prototyping of a sensor framework used to analyse the electrode’s behaviour and to monitor diverse electrode failure mechanisms, even during stimulation pulses, is presented. We focused on the electronic circuitry and data acquisition techniques required for a conceptual multi-sensor system. Functionality of single modules and a prototype framework have been demonstrated, but further work is needed to convert the prototype system into an implantable device. In vitro studies will be conducted first to verify sensor performance and reliability. PMID:28042815

Mechanical stresses and amorphization of ion-implanted diamond

NASA Astrophysics Data System (ADS)

Khmelnitsky, R. A.; Dravin, V. A.; Tal, A. A.; Latushko, M. I.; Khomich, A. A.; Khomich, A. V.; Trushin, A. S.; Alekseev, A. A.; Terentiev, S. A.

2013-06-01

Scanning white light interferometry and Raman spectroscopy were used to investigate the mechanical stresses and structural changes in ion-implanted natural diamonds with different impurity content. The uniform distribution of radiation defects in implanted area was obtained by the regime of multiple-energy implantation of keV He+ ions. A modification of Bosia's et al. (Nucl. Instrum. Meth. B 268 (2010) 2991) method for determining the internal stresses and the density variation in an ion-implanted diamond layer was proposed that suggests measuring, in addition to the surface swelling of a diamond plate, the radius of curvature of the plate. It is shown that, under multiple-energy implantation of He+, mechanical stresses in the implanted layer may be as high as 12 GPa. It is shown that radiation damage reaches saturation for the implantation fluence characteristic of amorphization of diamond but is appreciably lower than the graphitization threshold.

DNA-barcode directed capture and electrochemical metabolic analysis of single mammalian cells on a microelectrode array.

PubMed

Douglas, Erik S; Hsiao, Sonny C; Onoe, Hiroaki; Bertozzi, Carolyn R; Francis, Matthew B; Mathies, Richard A

2009-07-21

A microdevice is developed for DNA-barcode directed capture of single cells on an array of pH-sensitive microelectrodes for metabolic analysis. Cells are modified with membrane-bound single-stranded DNA, and specific single-cell capture is directed by the complementary strand bound in the sensor area of the iridium oxide pH microelectrodes within a microfluidic channel. This bifunctional microelectrode array is demonstrated for the pH monitoring and differentiation of primary T cells and Jurkat T lymphoma cells. Single Jurkat cells exhibited an extracellular acidification rate of 11 milli-pH min(-1), while primary T cells exhibited only 2 milli-pH min(-1). This system can be used to capture non-adherent cells specifically and to discriminate between visually similar healthy and cancerous cells in a heterogeneous ensemble based on their altered metabolic properties.

DNA-barcode directed capture and electrochemical metabolic analysis of single mammalian cells on a microelectrode array

PubMed Central

Douglas, Erik S.; Hsiao, Sonny C.; Onoe, Hiroaki; Bertozzi, Carolyn R.; Francis, Matthew B.; Mathies, Richard A.

2010-01-01

A microdevice is developed for DNA-barcode directed capture of single cells on an array of pH-sensitive microelectrodes for metabolic analysis. Cells are modified with membrane-bound single-stranded DNA, and specific single-cell capture is directed by the complementary strand bound in the sensor area of the iridium oxide pH microelectrodes within a microfluidic channel. This bifunctional microelectrode array is demonstrated for the pH monitoring and differentiation of primary T cells and Jurkat T lymphoma cells. Single Jurkat cells exhibited an extracellular acidification rate of 11 milli-pH min−1, while primary T cells exhibited only 2 milli-pH min−1. This system can be used to capture non-adherent cells specifically and to discriminate between visually similar healthy and cancerous cells in a heterogeneous ensemble based on their altered metabolic properties. PMID:19568668

Multi-electrode array technologies for neuroscience and cardiology

NASA Astrophysics Data System (ADS)

Spira, Micha E.; Hai, Aviad

2013-02-01

At present, the prime methodology for studying neuronal circuit-connectivity, physiology and pathology under in vitro or in vivo conditions is by using substrate-integrated microelectrode arrays. Although this methodology permits simultaneous, cell-non-invasive, long-term recordings of extracellular field potentials generated by action potentials, it is 'blind' to subthreshold synaptic potentials generated by single cells. On the other hand, intracellular recordings of the full electrophysiological repertoire (subthreshold synaptic potentials, membrane oscillations and action potentials) are, at present, obtained only by sharp or patch microelectrodes. These, however, are limited to single cells at a time and for short durations. Recently a number of laboratories began to merge the advantages of extracellular microelectrode arrays and intracellular microelectrodes. This Review describes the novel approaches, identifying their strengths and limitations from the point of view of the end users -- with the intention to help steer the bioengineering efforts towards the needs of brain-circuit research.

Multi-electrode array technologies for neuroscience and cardiology.

PubMed

Spira, Micha E; Hai, Aviad

2013-02-01

At present, the prime methodology for studying neuronal circuit-connectivity, physiology and pathology under in vitro or in vivo conditions is by using substrate-integrated microelectrode arrays. Although this methodology permits simultaneous, cell-non-invasive, long-term recordings of extracellular field potentials generated by action potentials, it is 'blind' to subthreshold synaptic potentials generated by single cells. On the other hand, intracellular recordings of the full electrophysiological repertoire (subthreshold synaptic potentials, membrane oscillations and action potentials) are, at present, obtained only by sharp or patch microelectrodes. These, however, are limited to single cells at a time and for short durations. Recently a number of laboratories began to merge the advantages of extracellular microelectrode arrays and intracellular microelectrodes. This Review describes the novel approaches, identifying their strengths and limitations from the point of view of the end users--with the intention to help steer the bioengineering efforts towards the needs of brain-circuit research.

Kron-Branin modelling of ultra-short pulsed signal microelectrode

NASA Astrophysics Data System (ADS)

Xu, Zhifei; Ravelo, Blaise; Liu, Yang; Zhao, Lu; Delaroche, Fabien; Vurpillot, Francois

2018-06-01

An uncommon circuit modelling of microelectrode for ultra-short signal propagation is developed. The proposed model is based on the Tensorial Analysis of Network (TAN) using the Kron-Branin (KB) formalism. The systemic graph topology equivalent to the considered structure problem is established by assuming as unknown variables the branch currents. The TAN mathematical solution is determined after the KB characteristic matrix identification. The TAN can integrate various structure physical parameters. As proof of concept, via hole ended microelectrodes implemented on Kapton substrate were designed, fabricated and tested. The 0.1-MHz-to-6-GHz S-parameter KB model, simulation and measurement are in good agreement. In addition, time-domain analyses with nanosecond duration pulse signals were carried out to predict the microelectrode signal integrity. The modelled microstrip electrode is usually integrated in the atom probe tomography. The proposed unfamiliar KB method is particularly beneficial with respect to the computation speed and adaptability to various structures.

Detachable glass microelectrodes for recording action potentials in active moving organs.

PubMed

Barbic, Mladen; Moreno, Angel; Harris, Tim D; Kay, Matthew W

2017-06-01

Here, we describe new detachable floating glass micropipette electrode devices that provide targeted action potential recordings in active moving organs without requiring constant mechanical constraint or pharmacological inhibition of tissue motion. The technology is based on the concept of a glass micropipette electrode that is held firmly during cell targeting and intracellular insertion, after which a 100-µg glass microelectrode, a "microdevice," is gently released to remain within the moving organ. The microdevices provide long-term recordings of action potentials, even during millimeter-scale movement of tissue in which the device is embedded. We demonstrate two different glass micropipette electrode holding and detachment designs appropriate for the heart (sharp glass microdevices for cardiac myocytes in rats, guinea pigs, and humans) and the brain (patch glass microdevices for neurons in rats). We explain how microdevices enable measurements of multiple cells within a moving organ that are typically difficult with other technologies. Using sharp microdevices, action potential duration was monitored continuously for 15 min in unconstrained perfused hearts during global ischemia-reperfusion, providing beat-to-beat measurements of changes in action potential duration. Action potentials from neurons in the hippocampus of anesthetized rats were measured with patch microdevices, which provided stable base potentials during long-term recordings. Our results demonstrate that detachable microdevices are an elegant and robust tool to record electrical activity with high temporal resolution and cellular level localization without disturbing the physiological working conditions of the organ. NEW & NOTEWORTHY Cellular action potential measurements within tissue using glass micropipette electrodes usually require tissue immobilization, potentially influencing the physiological relevance of the measurement. Here, we addressed this limitation with novel 100-µg detachable glass microelectrodes that can be precisely positioned to provide long-term measurements of action potential duration during unconstrained tissue movement. Copyright © 2017 the American Physiological Society.

Microfabricated injectable drug delivery system

DOEpatents

Krulevitch, Peter A.; Wang, Amy W.

2002-01-01

A microfabricated, fully integrated drug delivery system capable of secreting controlled dosages of multiple drugs over long periods of time (up to a year). The device includes a long and narrow shaped implant with a sharp leading edge for implantation under the skin of a human in a manner analogous to a sliver. The implant includes: 1) one or more micromachined, integrated, zero power, high and constant pressure generating osmotic engine; 2) low power addressable one-shot shape memory polymer (SMP) valves for switching on the osmotic engine, and for opening drug outlet ports; 3) microfabricated polymer pistons for isolating the pressure source from drug-filled microchannels; 4) multiple drug/multiple dosage capacity, and 5) anisotropically-etched, atomically-sharp silicon leading edge for penetrating the skin during implantation. The device includes an externally mounted controller for controlling on-board electronics which activates the SMP microvalves, etc. of the implant.

Dynamic, electronically switchable surfaces for membrane protein microarrays.

PubMed

Tang, C S; Dusseiller, M; Makohliso, S; Heuschkel, M; Sharma, S; Keller, B; Vörös, J

2006-02-01

Microarray technology is a powerful tool that provides a high throughput of bioanalytical information within a single experiment. These miniaturized and parallelized binding assays are highly sensitive and have found widespread popularity especially during the genomic era. However, as drug diagnostics studies are often targeted at membrane proteins, the current arraying technologies are ill-equipped to handle the fragile nature of the protein molecules. In addition, to understand the complex structure and functions of proteins, different strategies to immobilize the probe molecules selectively onto a platform for protein microarray are required. We propose a novel approach to create a (membrane) protein microarray by using an indium tin oxide (ITO) microelectrode array with an electronic multiplexing capability. A polycationic, protein- and vesicle-resistant copolymer, poly(l-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG), is exposed to and adsorbed uniformly onto the microelectrode array, as a passivating adlayer. An electronic stimulation is then applied onto the individual ITO microelectrodes resulting in the localized release of the polymer thus revealing a bare ITO surface. Different polymer and biological moieties are specifically immobilized onto the activated ITO microelectrodes while the other regions remain protein-resistant as they are unaffected by the induced electrical potential. The desorption process of the PLL-g-PEG is observed to be highly selective, rapid, and reversible without compromising on the integrity and performance of the conductive ITO microelectrodes. As such, we have successfully created a stable and heterogeneous microarray of biomolecules by using selective electronic addressing on ITO microelectrodes. Both pharmaceutical diagnostics and biomedical technology are expected to benefit directly from this unique method.

[Construction of a multiple-scale implant surface with super-hydrophilicity].

PubMed

Luo, Qiao-jie; Li, Xiao-dong; Huang, Ying; Zhao, Shi-fang

2012-05-01

To construct a multiple-scale organized implant surface with super-hydrophilicity. The SiC paper polished titanium disc was sandblasted and treated with HF/HNO₃ and HCl/H₂SO₄, then acid-etched with H₂SO₄/H₂O₂. The physicochemical properties of the surfaces were characterized by scanning electron microscope, static state contact angle and X-ray diffraction. MC3T3-E1 cells were used to evaluate the effects of the surface on the cell adhesion, proliferation and differentiation. The acid-etching process with a mixture of H₂SO₄/H₂O₂ superimposed the nano-scale structure on the micro-scale texture. The multiple-scale implant surface promoted its hydrophilicity and was more favorable to the responses of osteoprogenitor cells, characterized by increased DNA content, enhanced ALP activity and promoted OC production. A multiple-scale implant surface with super-hydrophilicity has been constructed in this study, which facilitates cell proliferation and adhesion.

Impression of multiple implants using photogrammetry: description of technique and case presentation.

PubMed

Peñarrocha-Oltra, David; Agustín-Panadero, Rubén; Bagán, Leticia; Giménez, Beatriz; Peñarrocha, María

2014-07-01

To describe a technique for registering the positions of multiple dental implants using a system based on photogrammetry. A case is presented in which a prosthetic treatment was performed using this technique. Three Euroteknika® dental implants were placed to rehabilitate a 55-year-old male patient with right posterior maxillary edentulism. Three months later, the positions of the implants were registered using a photogrammetry-based stereo-camera (PICcamera®). After processing patient and implant data, special abutments (PICabutment®) were screwed onto each implant. The PICcamera® was then used to capture images of the implant positions, automatically taking 150 images in less than 60 seconds. From this information a file was obtained describing the relative positions - angles and distances - of each implant in vector form. Information regarding the soft tissues was obtained from an alginate impression that was cast in plaster and scanned. A Cr-Co structure was obtained using CAD/CAM, and its passive fit was verified in the patient's mouth using the Sheffield test and the screw resistance test. Twelve months after loading, peri-implant tissues were healthy and no marginal bone loss was observed. The clinical application of this new system using photogrammetry to record the position of multiple dental implants facilitated the rehabilitation of a patient with posterior maxillary edentulism by means of a prosthesis with optimal fit. The prosthetic process was accurate, fast, simple to apply and comfortable for the patient.

Electrical properties of titanium dioxide nanoparticle on microelectrode: Gap size effect

NASA Astrophysics Data System (ADS)

Nadzirah, Sh.; Hashim, U.; Zakaria, M. R.; Rusop, M.

2018-05-01

TiO2 nanoparticle based interdigitated microelectrode was fabricated by spin-coating and conventional photolithography approaches. Aluminum metal was deposited by thermal evaporator on silicon dioxide substrate. The effect of aluminum microelectrode gap sizes (4, 5 and 6 µm) on the electrical performance was investigated using picoammeter. Extremely small output current values of three different gap sizes were acquired. A characteristic electrical behavior was observed for the studied geometry. The configuration demonstrated a reduction in the output current from 2.28E-10, 1.32E-9 and 2.38E-9 A with increasing gap size.

Microelectrode for energy and current control of nanotip field electron emitters

NASA Astrophysics Data System (ADS)

Lüneburg, S.; Müller, M.; Paarmann, A.; Ernstorfer, R.

2013-11-01

Emerging experiments and applications in electron microscopy, holography, and diffraction benefit from miniaturized electron guns for compact experimental setups. We present a highly compact microelectrode integrated field emitter that consists of a tungsten nanotip coated with a few micrometers thick polyimide film followed by a several nanometers thick gold film, both positioned behind the exposed emitter apex by approximately 10-30 μm. The control of the electric field strength at the nanometer scale tip apex allows suppression, extraction, and energy tuning of field-emitted electrons. The performance of the microelectrode is demonstrated experimentally and supported by numerical simulations.

Toward on-chip, in-cell recordings from cultured cardiomyocytes by arrays of gold mushroom-shaped microelectrodes

PubMed Central

Fendyur, Anna; Spira, Micha E.

2012-01-01

Cardiological research greatly rely on the use of cultured primary cardiomyocytes (CMs). The prime methodology to assess CM network electrophysiology is based on the use of extracellular recordings by substrate-integrated planar Micro-Electrode Arrays (MEAs). Whereas this methodology permits simultaneous, long-term monitoring of the CM electrical activity, it limits the information to extracellular field potentials (FPs). The alternative method of intracellular action potentials (APs) recordings by sharp- or patch-microelectrodes is limited to a single cell at a time. Here, we began to merge the advantages of planar MEA and intracellular microelectrodes. To that end we cultured rat CM on micrometer size protruding gold mushroom-shaped microelectrode (gMμEs) arrays. Cultured CMs engulf the gMμE permitting FPs recordings from individual cells. Local electroporation of a CM converts the extracellular recording configuration to attenuated intracellular APs with shape and duration similar to those recorded intracellularly. The procedure enables to simultaneously record APs from an unlimited number of CMs. The electroporated membrane spontaneously recovers. This allows for repeated recordings from the same CM a number of times (>8) for over 10 days. The further development of CM-gMμE configuration opens up new venues for basic and applied biomedical research. PMID:22936913

Impression of multiple implants using photogrammetry: Description of technique and case presentation

PubMed Central

Peñarrocha-Oltra, David; Agustín-Panadero, Rubén; Bagán, Leticia; Giménez, Beatriz

2014-01-01

Aim: To describe a technique for registering the positions of multiple dental implants using a system based on photogrammetry. A case is presented in which a prosthetic treatment was performed using this technique. Study Design: Three Euroteknika® dental implants were placed to rehabilitate a 55-year-old male patient with right posterior maxillary edentulism. Three months later, the positions of the implants were registered using a photogrammetry-based stereo-camera (PICcamera®). After processing patient and implant data, special abutments (PICabutment®) were screwed onto each implant. The PICcamera® was then used to capture images of the implant positions, automatically taking 150 images in less than 60 seconds. From this information a file was obtained describing the relative positions – angles and distances – of each implant in vector form. Information regarding the soft tissues was obtained from an alginate impression that was cast in plaster and scanned. A Cr-Co structure was obtained using CAD/CAM, and its passive fit was verified in the patient’s mouth using the Sheffield test and the screw resistance test. Results and Conclusions: Twelve months after loading, peri-implant tissues were healthy and no marginal bone loss was observed. The clinical application of this new system using photogrammetry to record the position of multiple dental implants facilitated the rehabilitation of a patient with posterior maxillary edentulism by means of a prosthesis with optimal fit. The prosthetic process was accurate, fast, simple to apply and comfortable for the patient. Key words:Dental implants, photogrammetry, dental impression technique, CAD/CAM. PMID:24608216

Evaluation of a Microelectrode Arrays for Neurotoxicity Testing Using a Chemical Training Set

EPA Science Inventory

Microelectrode array (MEA) approaches have been proposed as a tool for detecting functional changes in electrically active cells, including neurons, exposed to drugs, chemicals, or particles. However, conventional single well MEA systems lack the throughput necessary for screenin...

Quantitative Analysis of Rat Dorsal Root Ganglion Neurons Cultured on Microelectrode Arrays Based on Fluorescence Microscopy Image Processing.

PubMed

Mari, João Fernando; Saito, José Hiroki; Neves, Amanda Ferreira; Lotufo, Celina Monteiro da Cruz; Destro-Filho, João-Batista; Nicoletti, Maria do Carmo

2015-12-01

Microelectrode Arrays (MEA) are devices for long term electrophysiological recording of extracellular spontaneous or evocated activities on in vitro neuron culture. This work proposes and develops a framework for quantitative and morphological analysis of neuron cultures on MEAs, by processing their corresponding images, acquired by fluorescence microscopy. The neurons are segmented from the fluorescence channel images using a combination of segmentation by thresholding, watershed transform, and object classification. The positioning of microelectrodes is obtained from the transmitted light channel images using the circular Hough transform. The proposed method was applied to images of dissociated culture of rat dorsal root ganglion (DRG) neuronal cells. The morphological and topological quantitative analysis carried out produced information regarding the state of culture, such as population count, neuron-to-neuron and neuron-to-microelectrode distances, soma morphologies, neuron sizes, neuron and microelectrode spatial distributions. Most of the analysis of microscopy images taken from neuronal cultures on MEA only consider simple qualitative analysis. Also, the proposed framework aims to standardize the image processing and to compute quantitative useful measures for integrated image-signal studies and further computational simulations. As results show, the implemented microelectrode identification method is robust and so are the implemented neuron segmentation and classification one (with a correct segmentation rate up to 84%). The quantitative information retrieved by the method is highly relevant to assist the integrated signal-image study of recorded electrophysiological signals as well as the physical aspects of the neuron culture on MEA. Although the experiments deal with DRG cell images, cortical and hippocampal cell images could also be processed with small adjustments in the image processing parameter estimation.

Evaluation of adsorption capacities of humic acids extracted from Algerian soil on polyaniline for application to remove pollutants such as Cd(II), Zn(II) and Ni(II) and characterization with cavity microelectrode.

PubMed

Terbouche, Achour; Ramdane-Terbouche, Chafia Ait; Hauchard, Didier; Djebbar, Safia

2011-01-01

The adsorption capacities of new humic acids isolated from Yakouren forest (YHA) and Sahara (Tamenrasset: THA) soils (Algeria) and commercial humic acid (PFHA) on polyaniline emeraldine base (PEB) were studied at pH 6.6. Also the adsorption of heavy metals such as Cd2+, Zn2+ and Ni2+ on humic acid-polyaniline systems (HA-PEB) was investigated at the same conditions. HA-PEB compounds were characterized by scanning electron microscopy (SEM), infrared spectrometry and cavity microelectrode. In addition, batch adsorption and cavity microelectrode were used in the adsorption study of Cd2+, Zn2+ and Ni2+ on HA-PEB. To develop biocaptors of polluting metals using a cavity microelectrode modified by HA-PEB systems, the adsorption kinetic and adsorption capacity were investigated. The SEM analysis showed that the presence of humic acid affected the PEB surface and caused the formation of a granular morphology. The maximum adsorption capacities (q(max)) of PFHA, THA and YHA determined by adsorption isotherms were 91.31, 132.1 and 151.0 mg/g, respectively. Batch adsorption results showed that q(max) of Cd2+, Zn2+ and Ni2+ on HA-PEB followed the order: THA-PEB > YHA-PEB > PFHA-PEB. The voltammograms obtained with HA-PEB modified cavity microelectrode showed the appearance of new redox couples reflecting the adsorption of HA on PEB. Metal-humic acid-polyaniline voltammograms were characterized by appearance of oxidation-reduction couples or reduction wave corresponding to metal. Finally, the result may be exploited to develop a biocaptor based on the cavity microelectrode amended by THA-PEB and YHA-PEB.

PEDOT-CNT coated electrodes stimulate retinal neurons at low voltage amplitudes and low charge densities

NASA Astrophysics Data System (ADS)

Samba, R.; Herrmann, T.; Zeck, G.

2015-02-01

Objective. The aim of this study was to compare two different microelectrode materials—the conductive polymer composite poly-3,4-ethylenedioxythiophene (PEDOT)-carbon nanotube(CNT) and titanium nitride (TiN)—at activating spikes in retinal ganglion cells in whole mount rat retina through stimulation of the local retinal network. Stimulation efficacy of the microelectrodes was analyzed by comparing voltage, current and transferred charge at stimulation threshold. Approach. Retinal ganglion cell spikes were recorded by a central electrode (30 μm diameter) in the planar grid of an electrode array. Extracellular stimulation (monophasic, cathodic, 0.1-1.0 ms) of the retinal network was performed using constant voltage pulses applied to the eight surrounding electrodes. The stimulation electrodes were equally spaced on the four sides of a square (400 × 400 μm). Threshold voltage was determined as the pulse amplitude required to evoke network-mediated ganglion cell spiking in a defined post stimulus time window in 50% of identical stimulus repetitions. For the two electrode materials threshold voltage, transferred charge at threshold, maximum current and the residual current at the end of the pulse were compared. Main results. Stimulation of retinal interneurons using PEDOT-CNT electrodes is achieved with lower stimulation voltage and requires lower charge transfer as compared to TiN. The key parameter for effective stimulation is a constant current over at least 0.5 ms, which is obtained by PEDOT-CNT electrodes at lower stimulation voltage due to its faradaic charge transfer mechanism. Significance. In neuroprosthetic implants, PEDOT-CNT may allow for smaller electrodes, effective stimulation in a safe voltage regime and lower energy-consumption. Our study also indicates, that the charge transferred at threshold or the charge injection capacity per se does not determine stimulation efficacy.

In Vivo Comparison of Norepinephrine and Dopamine Release in Rat Brain by Simultaneous Measurements with Fast-Scan Cyclic Voltammetry

PubMed Central

Park, Jinwoo; Takmakov, Pavel; Wightman, R. Mark

2011-01-01

Brain norepinephrine and dopamine regulate a variety of critical behaviors such as stress, learning, memory, and drug addiction. Here, we demonstrate differences in the regulation of in vivo neurotransmission for dopamine in the anterior nucleus accumbens (NAc) and norepinephrine in the ventral bed nucleus of the stria terminalis (vBNST) of the anesthetized rat. Release of the two catecholamines was measured simultaneously using fast-scan cyclic voltammetry (FSCV) at two different carbon-fiber microelectrodes, each implanted in the brain region of interest. Simultaneous dopamine and norepinephrine release was evoked by electrical stimulation of a region where the ventral noradrenergic bundle (VNB), the pathway of noradrenergic neurons, courses through the ventral tegmental area/substantia nigra (VTA/SN), the origin of dopaminergic cell bodies. The release and uptake of norepinephrine in the vBNST were both significantly slower than for dopamine in the NAc. Pharmacological manipulations in the same animal demonstrated that the two catecholamines are differently regulated. The combination of a dopamine autoreceptor antagonist and amphetamine significantly increased basal extracellular dopamine whereas a norepinephrine autoreceptor antagonist and amphetamine did not change basal norepinephrine concentration. α-Methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, decreased electrically evoked dopamine release faster than norepinephrine. The dual-microelectrode FSCV technique along with anatomical and pharmacological evidence confirms that dopamine in the NAc and norepinephrine in the vBNST can be monitored selectively and simultaneously in the same animal. The high temporal and spatial resolution of the technique enabled us to examine differences in the dynamics of extracellular norepinephrine and dopamine concurrently in two different limbic structures. PMID:21933188

Task-Dependent Changes in Cross-Level Coupling between Single Neurons and Oscillatory Activity in Multiscale Networks

PubMed Central

Canolty, Ryan T.; Ganguly, Karunesh; Carmena, Jose M.

2012-01-01

Understanding the principles governing the dynamic coordination of functional brain networks remains an important unmet goal within neuroscience. How do distributed ensembles of neurons transiently coordinate their activity across a variety of spatial and temporal scales? While a complete mechanistic account of this process remains elusive, evidence suggests that neuronal oscillations may play a key role in this process, with different rhythms influencing both local computation and long-range communication. To investigate this question, we recorded multiple single unit and local field potential (LFP) activity from microelectrode arrays implanted bilaterally in macaque motor areas. Monkeys performed a delayed center-out reach task either manually using their natural arm (Manual Control, MC) or under direct neural control through a brain-machine interface (Brain Control, BC). In accord with prior work, we found that the spiking activity of individual neurons is coupled to multiple aspects of the ongoing motor beta rhythm (10–45 Hz) during both MC and BC, with neurons exhibiting a diversity of coupling preferences. However, here we show that for identified single neurons, this beta-to-rate mapping can change in a reversible and task-dependent way. For example, as beta power increases, a given neuron may increase spiking during MC but decrease spiking during BC, or exhibit a reversible shift in the preferred phase of firing. The within-task stability of coupling, combined with the reversible cross-task changes in coupling, suggest that task-dependent changes in the beta-to-rate mapping play a role in the transient functional reorganization of neural ensembles. We characterize the range of task-dependent changes in the mapping from beta amplitude, phase, and inter-hemispheric phase differences to the spike rates of an ensemble of simultaneously-recorded neurons, and discuss the potential implications that dynamic remapping from oscillatory activity to spike rate and timing may hold for models of computation and communication in distributed functional brain networks. PMID:23284276

A comparison of two surgical approaches in functional neurosurgery: individualized versus conventional stereotactic frames.

PubMed

Matzke, Cornelia; Lindner, Dirk; Schwarz, Johannes; Classen, Joseph; Hammer, Niels; Weise, David; Rumpf, Jost-Julian; Fritzsch, Dominik; Meixensberger, Jürgen; Winkler, Dirk

2015-01-01

The individualized Starfix® miniframe belongs to a new generation of stereotactic systems enabling high-precision electrode placement with considerably better time-efficiency in deep brain stimulation (DBS). We evaluated the usability and reliability of this novel technique in patients with idiopathic Parkinson's disease (IPD) and compared surgical and clinical results with those obtained in a historical group in which a conventional stereotactic frame was employed. Sixty patients underwent surgery for implantation of DBS electrodes in the subthalamic nucleus. In 31 of them (group I) a conventional Zamorano-Dujovny frame was used and in 29 of them (group II) a Starfix® miniframe was used. Image fusion of preoperatively acquired 3D T1w and T2w 1.5 T MR-image series was used for the targeting procedure. Placement of the test electrodes and permanent electrodes corresponded to standard functional neurosurgery and included microelectrode recording and macrostimulation. Clinical (L-Dopa equivalent dose, United Parkinson's disease rating scale part III) and time for surgical electrode implantation were evaluated postoperatively in a 3-, 6- and 12-month follow-up. Twelve months postoperatively, L-Dopa dose was significantly reduced from 685.19 to 205.88 mg/day and from 757.92 to 314.42 mg/day in groups I and II, respectively. A comparable reduction of the LED could be observed 1 year after surgery. Motor function has improved in a significant and identical manner with 59% (group I) and 61% (group II). Besides clinical effects by stimulation therapy there was a significantly reduced surgery time required for electrode implantation using the Starfix® miniframe (group I: 234.1 min, group II: 173.6 min; p < 0.001). Individualized miniframes such as the Starfix® miniframe allow implantation of DBS electrodes in IPD that is equally effective as conventional systems. The time efficiency achieved in surgery using of the Starfix® system helps to minimize patients' discomfort during DBS surgery.

Evaluation of Multi-Well Microelectrode Arrays for Neurotoxicity Screening Using a Chemical Training Set

EPA Science Inventory

Microelectrode array (MEA) approaches have been proposed as a tool for detecting functional changes in electrically-excitable cells, including neurons, exposed to drugs, chemical or particles. However, conventional single well-MEA systems lack the throughput necessary for screen...

Simultaneous/Selective Detection of Dopamine and Ascorbic Acid at Synthetic Zeolite-Modified/Graphite-Epoxy Composite Macro/Quasi-Microelectrodes

PubMed Central

Ilinoiu, Elida Cristina; Manea, Florica; Serra, Pier Andrea; Pode, Rodica

2013-01-01

The present paper aims to miniaturize a graphite-epoxy and synthetic zeolite-modified graphite-epoxy composite macroelectrode as a quasi-microelectrode aiming in vitro and also, envisaging in vivo simultaneous electrochemical detection of dopamine (DA) and ascorbic acid (AA) neurotransmitters, or DA detection in the presence of AA. The electrochemical behavior and the response of the designed materials to the presence of dopamine and ascorbic acid without any protective membranes were studied by cyclic voltammetry and constant-potential amperometry techniques. The catalytic effect towards dopamine detection was proved for the synthetic zeolite-modified graphite-epoxy composite quasi-microelectrode, allowing increasing the sensitivity and selectivity for this analyte detection, besides a possible electrostatic attraction between dopamine cation and the negative surface of the synthetic zeolite and electrostatic repulsion with ascorbic acid anion. Also, the synthetic zeolite-modified graphite-epoxy composite quasi-microelectrode gave the best electroanalytical parameters for dopamine detection using constant-potential amperometry, the most useful technique for practical applications. PMID:23736851

A Microchip-based Endothelium Mimic Utilizing Open Reservoirs for Cell Immobilization and Integrated Carbon Ink Microelectrodes for Detection

PubMed Central

Hulvey, Matthew K; Martin, R. Scott

2010-01-01

This paper describes the fabrication and characterization of a microfluidic device that utilizes a reservoir-based approach for endothelial cell immobilization and integrated embedded carbon ink microelectrodes for the amperometric detection of extracellular nitric oxide (NO) release. The design utilizes a buffer channel to continuously introduce buffer or a plug of stimulant to the reservoir as well as a separate sampling channel that constantly withdraws buffer from the reservoir and over the microelectrode. A steel pin is used for both the fluidic connection to the sampling channel and to provide a quasi-reference electrode for the carbon ink microelectrode. Characterization of the device was performed using NO standards produced from a NONOate salt. Finally, NO release from a layer of immobilized endothelial cells was monitored and quantified using the system. This system holds promise as a means to electrochemically detect extracellular NO release from endothelial cells in either an array of reservoirs or concurrently with fluorescence-based intracellular NO measurements. PMID:18989663

Microelectrode Array Microscopy: Investigation of Dynamic Behavior of Localized Corrosion at Type 304 Stainless Steel Surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tedd E. Lister; Patrick J. Pinhero

2005-03-01

Scanning electrochemical microscopy (SECM) and a recently developed microelectrode array microscope have been used to study localized corrosion and electron-transfer characteristics of native oxide layers of type 304 stainless steels. The I-/I3- redox couple was employed as a mediator and allowed sensitive detection of oxide breakdown events. In solutions containing I-, a signal at the microelectrode was observed on type 304 stainless steel surfaces at active pitting corrosion sites. Under conditions where pitting corrosion occurs, SECM was used to track the temporal characteristics of the reaction in a spatial manner. However, because of the time required to create an image,more » much of the temporal information was not obtained. To improve the temporal resolution of the measurement, microelectrode array microscopy (MEAM) was developed as a parallel method of performing SECM. The demonstration shown reveals the potential of MEAM for analysis of surface chemistry on temporal and spatial domains.« less

Simultaneous/selective detection of dopamine and ascorbic acid at synthetic zeolite-modified/graphite-epoxy composite macro/quasi-microelectrodes.

PubMed

Ilinoiu, Elida Cristina; Manea, Florica; Serra, Pier Andrea; Pode, Rodica

2013-06-03

The present paper aims to miniaturize a graphite-epoxy and synthetic zeolite-modified graphite-epoxy composite macroelectrode as a quasi-microelectrode aiming in vitro and also, envisaging in vivo simultaneous electrochemical detection of dopamine (DA) and ascorbic acid (AA) neurotransmitters, or DA detection in the presence of AA. The electrochemical behavior and the response of the designed materials to the presence of dopamine and ascorbic acid without any protective membranes were studied by cyclic voltammetry and constant-potential amperometry techniques. The catalytic effect towards dopamine detection was proved for the synthetic zeolite-modified graphite-epoxy composite quasi-microelectrode, allowing increasing the sensitivity and selectivity for this analyte detection, besides a possible electrostatic attraction between dopamine cation and the negative surface of the synthetic zeolite and electrostatic repulsion with ascorbic acid anion. Also, the synthetic zeolite-modified graphite-epoxy composite quasi-microelectrode gave the best electroanalytical parameters for dopamine detection using constant-potential amperometry, the most useful technique for practical applications.

Chronic, percutaneous connector for electrical recording and stimulation with microelectrode arrays.

PubMed

Shah, Kedar G; Lee, Kye Young; Tolosa, Vanessa; Tooker, Angela; Felix, Sarah; Benett, William; Pannu, Satinderpall

2014-01-01

The translation of advances in neural stimulation and recording research into clinical practice hinges on the ability to perform chronic experiments in awake and behaving animal models. Advances in microelectrode array technology, most notably flexible polymer arrays, have significantly improved reliability of the neural interface. However, electrical connector technology has lagged and is prone to failure from non-biocompatibility, large size, contamination, corrosion, and difficulty of use. We present a novel chronic, percutaneous electrical connector system that is suitable for neural stimulation and recording. This system features biocompatible materials, low connect and disconnect forces, passive alignment, and a protective cap during non-use. We have successfully designed, assembled, and tested in vitro both a 16-channel system and a high density 64-channel system. Custom, polyimide, 16-channel, microelectrode arrays were electrically assembled with the connector system and tested using cyclic voltammetry and electrochemical impedance spectroscopy. This connector system is versatile and can be used with a variety of microelectrode array technologies for chronic studies.

A comparison of electrochemically pre-treated and spark-platinized carbon fiber microelectrode. Measurement of 8-oxo-7,8-dihydro-2'-deoxyguanosine in human urine and plasma.

PubMed

Bartosova, Z; Riman, D; Halouzka, V; Vostalova, J; Simanek, V; Hrbac, J; Jirovsky, D

2016-09-07

A novel method of carbon fiber microelectrode activation using spark discharge was demonstrated and compared to conventional electrochemical pretreatment by potential cycling. The spark discharge was performed at 800 V between the microelectrode connected to positive pole of the power supply and platinum counter electrode. Spark discharge led both to trimming of the fiber tip into conical shape and to the modification of carbon fiber microelectrode with platinum, as proven by scanning electron microscopy and electron dispersive X-ray spectroscopy. After the characterization of electrochemical properties using ferricyanide voltammetry, the activated electrodes were used for electrochemical analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidative stress marker. Subnanomolar detection limits (0.55 nmol L(-1)) in high-performance liquid chromatography were achieved for spark platinized electrodes incorporated into the flow detection cell. Copyright © 2016 Elsevier B.V. All rights reserved.

Measurement of intracellular chloride in guinea-pig vas deferens by ion analysis, 36chloride and micro-electrodes

PubMed Central

Aickin, C. Claire; Brading, Alison F.

1982-01-01

1. Cl-sensitive micro-electrodes were used to measure the intracellular Cl activity (aCli) in smooth muscle cells of the guinea-pig vas deferens. The values obtained were compared with those of intracellular Cl (Cli) found by both ion analysis and 36Cl efflux. 2. Various combinations of filling solution for recording membrane potential (Em), and type of micro-electrode were tested. The most successful, which allowed continuous recording of aCli for several hours, was a double-barrelled electrode using the reference liquid ion exchanger (RLIE; Thomas & Cohen, 1981). However, aCli measured both by simultaneous impalements of separate cells with Cl-sensitive and conventional micro-electrodes, and by double-barrelled micro-electrodes, was about 42 mM in normal Krebs solution. This is five times higher than the value from a passive distribution. ECl was about -24 mV, more than 40 mV positive to Em. 3. On complete removal of extracellular Cl (Clo), aCli fell to an apparent level of about 3 mM. If this represents interference from other anions, the maximum error in ECl measured in normal Krebs solution is 2·5 mV. Replacement of Clo caused a rapid increase in aCli. This must be caused by an active transport of Cl- ions into the cell against their electrochemical gradient. 4. The stabilized values of aCli measured at different levels of Clo agree surprisingly well with aCli estimated from ion analysis and 36Cl efflux, assuming that the intracellular activity coefficient was the same as measured in the normal Krebs solution. The relationship of aCli to Clo was hyperbolic. 5. It is concluded that Cl-sensitive micro-electrodes accurately measure aCli in smooth muscle cells. The remarkable agreement between the direct and indirect methods of measuring Cli suggests that Cl- ions are not bound to a significant extent and that the compartment seen by the micro-electrodes is probably representative of the whole cell. PMID:7108787

Microelectrode for energy and current control of nanotip field electron emitters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lüneburg, S.; Müller, M., E-mail: m.mueller@fhi-berlin.mpg.de; Paarmann, A., E-mail: alexander.paarmann@fhi-berlin.mpg.de

2013-11-18

Emerging experiments and applications in electron microscopy, holography, and diffraction benefit from miniaturized electron guns for compact experimental setups. We present a highly compact microelectrode integrated field emitter that consists of a tungsten nanotip coated with a few micrometers thick polyimide film followed by a several nanometers thick gold film, both positioned behind the exposed emitter apex by approximately 10–30 μm. The control of the electric field strength at the nanometer scale tip apex allows suppression, extraction, and energy tuning of field-emitted electrons. The performance of the microelectrode is demonstrated experimentally and supported by numerical simulations.

In Situ Identification and Stratification of Monochloramine Inhibition Effects on Nitrifying Biofilms as Determined by the Use of Microelectrodes

EPA Science Inventory

The nitrifying biofilm grown in an annular biofilm reactor and the microbial deactivation achieved after monochloramine treatment were investigated using microelectrodes. The nitrifying biofilm ammonium microprofile was measured and the effect of monochloramine on nitrifying bio...

Direct-write assembly of microperiodic planar and spanning ITO microelectrodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahn, Bok Y; Lorang, David J; Duoss, Eric B.

2010-01-01

Printed Sn-doped In{sub 2}O{sub 3} (ITO) microelectrodes are fabricated by direct-write assembly of sol–gel inks with varying concentration. This maskless, non-lithographic approach provides a facile route to patterning transparent conductive features in planar arrays and spanning architectures.

Characterization of Early Cortical Neural Network Development in Multiwell Microelectrode Array Plates

EPA Science Inventory

We examined the development of neural network activity using microelectrode array (MEA) recordings made in multi-well MEA plates (mwMEAs) over the first 12 days in vitro (DIV). In primary cortical cultures made from postnatal rats, action potential spiking activity was essentiall...

Multiple Ion Implantation Effects on Wear and Wet Ability of Polyethylene Based Polymers

NASA Astrophysics Data System (ADS)

Torrisi, L.; Visco, A. M.; Campo, N.

2004-10-01

Polyethylene based polymers were ion implanted with multiple irradiations of different ions (N+, Ar+ and Kr+) at energies between 30 keV and 300 keV and doses ranging between 1013 and 1016 ions/cm2. The ion implantation dehydrogenises the polyethylene inducing cross-link effects in the residual polymer carbons. At high doses the irradiated surface show properties similar to graphite surfaces. The depth of the modified layers depends on the ion range in polyethylene at the incident ion energy. The chemical modification depends on the implanted doses and on the specie of the incident ions. A "pin-on-disc" machine was employed to measure the polymer wear against AISI-316 L stainless steel. A "contact-angle-test" machine was employed to measure the wet ability of the polymer surface for 1 μl pure water drop. Measurements demonstrate that the multiple ion implantation treatments decrease the surface wear and the surface wetting and produce a more resistant polymer surface. The properties of the treated surfaces improves the polymer functionality for many bio-medical applications, such as those relative to the polyethylene friction discs employed in knee and hip prosthesis joints. The possibility to use multiply ion implantations of polymers with traditional ion implanters and with laser ion sources producing plasmas is investigated.

An implantable myoelectric sensor based prosthesis control system.

PubMed

DeMichele, Glenn A; Troyk, Philip R; Kerns, Douglas A; Weir, Richard

2006-01-01

We present progress on the design and testing of an upper-extremity prosthesis control system based on implantable myoelectric sensors. The implant consists of a single silicon chip packaged with transmit and receive coils. Forward control telemetry to, and reverse EMG data telemetry from multiple implants has been demonstrated.

Highly Stable Glassy Carbon Interfaces for Long-Term Neural Stimulation and Low-Noise Recording of Brain Activity

PubMed Central

Vomero, Maria; Castagnola, Elisa; Ciarpella, Francesca; Maggiolini, Emma; Goshi, Noah; Zucchini, Elena; Carli, Stefano; Fadiga, Luciano; Kassegne, Sam; Ricci, Davide

2017-01-01

We report on the superior electrochemical properties, in-vivo performance and long term stability under electrical stimulation of a new electrode material fabricated from lithographically patterned glassy carbon. For a direct comparison with conventional metal electrodes, similar ultra-flexible, micro-electrocorticography (μ-ECoG) arrays with platinum (Pt) or glassy carbon (GC) electrodes were manufactured. The GC microelectrodes have more than 70% wider electrochemical window and 70% higher CTC (charge transfer capacity) than Pt microelectrodes of similar geometry. Moreover, we demonstrate that the GC microelectrodes can withstand at least 5 million pulses at 0.45 mC/cm2 charge density with less than 7.5% impedance change, while the Pt microelectrodes delaminated after 1 million pulses. Additionally, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) was selectively electrodeposited on both sets of devices to specifically reduce their impedances for smaller diameters (<60 μm). We observed that PEDOT-PSS adhered significantly better to GC than Pt, and allowed drastic reduction of electrode size while maintaining same amount of delivered current. The electrode arrays biocompatibility was demonstrated through in-vitro cell viability experiments, while acute in vivo characterization was performed in rats and showed that GC microelectrode arrays recorded somatosensory evoked potentials (SEP) with an almost twice SNR (signal-to-noise ratio) when compared to the Pt ones. PMID:28084398

Carbon Nanospikes Grown on Metal Wires as Microelectrode Sensors for Dopamine

PubMed Central

Zestos, Alexander G.; Yang, Cheng; Jacobs, Christopher B.; Hensley, Dale; Venton, B. Jill

2015-01-01

Carbon nanomaterials are advantageous as electrodes for neurotransmitter detection, but the difficulty of nanomaterials deposition on electrode substrates limits the reproducibility and future applications. In this study, we used plasma enhanced chemical vapor deposition (PECVD) to directly grow a thin layer of carbon nanospikes (CNS) on cylindrical metal substrates. No catalyst is required and the CNS surface coverage is uniform over the cylindrical metal substrate. The CNS growth was characterized on several metallic substrates including tantalum, niobium, palladium, and nickel wires. Using fast-scan cyclic voltammetry (FSCV), bare metal wires could not detect 1 μM dopamine while carbon nanospike coated wires could. The highest sensitivity and optimized S/N ratio was recorded from carbon nanospike-tantalum (CNS-Ta) microwires grown for 7.5 minutes, which had a LOD of 8 ± 2 nM for dopamine with FSCV. CNS-Ta microelectrodes were more reversible and had a smaller ΔEp for dopamine than carbon-fiber microelectrodes, suggesting faster electron transfer kinetics. The kinetics of dopamine redox were adsorption controlled at CNS-Ta microelectrodes and repeated electrochemical measurements displayed stability for up to ten hours in vitro and over a ten day period as well. The oxidation potential was significantly different for ascorbic acid and uric acid compared to dopamine. Growing carbon nanospikes on metal wires is a promising method to produce uniformly-coated, carbon nanostructured cylindrical microelectrodes for sensitive dopamine detection. PMID:26389138

Acute changes associated with electrode insertion measured with optical coherence microscopy

NASA Astrophysics Data System (ADS)

Hammer, Daniel X.; Lozzi, Andrea; Boretsky, Adam; Agrawal, Anant; Welle, Cristin G.

2016-03-01

Despite advances in functional neural imaging, penetrating microelectrodes provide the most direct interface for the extraction of neural signals from the nervous system and are a critical component of many high degree-of-freedom braincomputer interface devices. Electrode insertion is a traumatic event that elicits a complex neuroinflammatory response. In this investigation we applied optical coherence microscopy (OCM), particularly optical coherence angiography (OCA), to characterize the immediate tissue response during microelectrode insertion. Microelectrodes of varying dimension and footprint (one-, two-, and four-shank) were inserted into mouse motor cortex beneath a window after craniotomy surgery. The microelectrodes were inserted in 3-4 steps at 15-20°, with approximately 250 μm linear insertion distance for each step. Before insertion and between each step, OCM datasets were collected, including for quantitative capillary velocimetry. A cohort of control animals without microelectrode insertion was also imaged over a similar time period (2-3 hours). Mechanical tissue deformation was observed in all the experimental animals. The quantitative angiography results varied across animals, and were not correlated with device dimensions. In some cases, localized flow drop-out was observed in a small region surrounding the electrode, while in other instances a global disruption in flow occurred, perhaps as a result of large vessel compression caused by mechanical pressure. OCM is a tool that can be used in various neurophotonics applications, including quantification of the neuroinflammatory response to penetrating electrode insertion.

Guiding pancreatic beta cells to target electrodes in a whole-cell biosensor for diabetes.

PubMed

Pedraza, Eileen; Karajić, Aleksandar; Raoux, Matthieu; Perrier, Romain; Pirog, Antoine; Lebreton, Fanny; Arbault, Stéphane; Gaitan, Julien; Renaud, Sylvie; Kuhn, Alexander; Lang, Jochen

2015-10-07

We are developing a cell-based bioelectronic glucose sensor that exploits the multi-parametric sensing ability of pancreatic islet cells for the treatment of diabetes. These cells sense changes in the concentration of glucose and physiological hormones and immediately react by generating electrical signals. In our sensor, signals from multiple cells are recorded as field potentials by a micro-electrode array (MEA). Thus, cell response to various factors can be assessed rapidly and with high throughput. However, signal quality and consequently overall sensor performance rely critically on close cell-electrode proximity. Therefore, we present here a non-invasive method of further exploiting the electrical properties of these cells to guide them towards multiple micro-electrodes via electrophoresis. Parameters were optimized by measuring the cell's zeta potential and modeling the electric field distribution. Clonal and primary mouse or human β-cells migrated directly to target electrodes during the application of a 1 V potential between MEA electrodes for 3 minutes. The morphology, insulin secretion, and electrophysiological characteristics were not altered compared to controls. Thus, cell manipulation on standard MEAs was achieved without introducing any external components and while maintaining the performance of the biosensor. Since the analysis of the cells' electrical activity was performed in real time via on-chip recording and processing, this work demonstrates that our biosensor is operational from the first step of electrically guiding cells to the final step of automatic recognition. Our favorable results with pancreatic islets, which are highly sensitive and fragile cells, are encouraging for the extension of this technique to other cell types and microarray devices.

A Multiplexed Assay for Determination of Neurotoxicant Effects on Spontaneous Network Activity and Viability from Microelectrode Arrays.

EPA Science Inventory

Microelectrode array (MEA) recordings are increasingly being used as an in vitro method to detect and characterize the ability of drugs, chemicals and particles to cause neurotoxicity. While effects of compounds on spontaneous network activity is easily determined by MEA recordin...

Neurotoxicity testing using Microelectrode Arrays (MEAs): a growing trend

EPA Science Inventory

Microelectrode arrays (MEAs) are groups of extracellular electrodes that are 10-30 microns in diameter and can be utilized in vivo or in vitro. For in vitro uses, an MEA typically contains up to 64 electrodes and can be utilized to measure the activity of cells and tissues that a...

Low Frequency Activity of Cortical Networks on Microelectrode Arrays is Differentially Altered by Bicuculline and Carbaryl

EPA Science Inventory

Thousands of chemicals need to be characterized for their neurotoxicity potential. Neurons grown on microelectrode arrays (MEAs) are an in vitro model used to screen chemicals for functional effects on neuronal networks. Typically, after removal of low frequency components, effec...

Effects of Organophosphorus Flame Retardants on Spontaneous Activity in Neuronal Networks Grown on Microelectrode Arrays

EPA Science Inventory

EFFECTS OF ORGANOPHOSPHORUS FLAME RETARDANTS ON SPONTANEOUS ACTIVITY IN NEURONAL NETWORKS GROWN ON MICROELECTRODE ARRAYS TJ Shafer1, K Wallace1, WR Mundy1, M Behl2,. 1Integrated Systems Toxicology Division, NHEERL, USEPA, RTP, NC, USA, 2National Toxicology Program, NIEHS, RTP, NC...

In–situ Spatiotemporal Chemical Reactions at Water-Solid Interfacial Processes using Microelectrode Techniques: from Biofilm to Metal Corrosion

EPA Science Inventory

Recent developments in microscale sensors allows the non-destructive and in–situ measurement of both the absolute and changes in chemical concentrations in engineered and natural aquatic systems. Microelectrodes represent a unique tool for studying in–situ chemical reactions in b...

Wide-bore 1.5 T MRI-guided deep brain stimulation surgery: initial experience and technique comparison.

PubMed

Sillay, Karl A; Rusy, Deborah; Buyan-Dent, Laura; Ninman, Nancy L; Vigen, Karl K

2014-12-01

We report results of the initial experience with magnetic resonance image (MRI)-guided implantation of subthalamic nucleus (STN) deep brain stimulating (DBS) electrodes at the University of Wisconsin after having employed frame-based stereotaxy with previously available MR imaging techniques and microelectrode recording for STN DBS surgeries. Ten patients underwent MRI-guided DBS implantation of 20 electrodes between April 2011 and March 2013. The procedure was performed in a purpose-built intraoperative MRI suite configured specifically to allow MRI-guided DBS, using a wide-bore (70 cm) MRI system. Trajectory guidance was accomplished with commercially available system consisting of an MR-visible skull-mounted aiming device and a software guidance system processing intraoperatively acquired iterative MRI scans. A total of 10 patients (5 male, 5 female)-representative of the Parkinson Disease (PD) population-were operated on with standard technique and underwent 20 electrode placements under MRI-guided bilateral STN-targeted DBS placement. All patients completed the procedure with electrodes successfully placed in the STN. Procedure time improved with experience. Our initial experience confirms the safety of MRI-guided DBS, setting the stage for future investigations combining physiology and MRI guidance. Further follow-up is required to compare the efficacy of the MRI-guided surgery cohort to that of traditional frame-based stereotaxy. Copyright © 2014 Elsevier B.V. All rights reserved.

Using stereophotogrammetric technology for obtaining intraoral digital impressions of implants.

PubMed

Pradíes, Guillermo; Ferreiroa, Alberto; Özcan, Mutlu; Giménez, Beatriz; Martínez-Rus, Francisco

2014-04-01

The procedure for making impressions of multiple implants continues to be a challenge, despite the various techniques proposed to date. The authors' objective in this case report is to describe a novel digital impression method for multiple implants involving the use of stereophotogrammetric technology. The authors present three cases of patients who had multiple implants in which the impressions were obtained with this technology. Initially, a stereo camera with an infrared flash detects the position of special flag abutments screwed into the implants. This process is based on registering the x, y and z coordinates of each implant and the distances between them. This information is converted into a stereolithographic (STL) file. To add the soft-tissue information, the user must obtain another STL file by using an intraoral or extraoral scanner. In the first case presented, this information was acquired from the plaster model with an extraoral scanner; in the second case, from a Digital Imaging and Communication in Medicine (DICOM) file of the plaster model obtained with cone-beam computed tomography; and in the third case, through an intraoral digital impression with a confocal scanner. In the three cases, the frameworks manufactured from this technique showed a correct clinical passive fit. At follow-up appointments held six, 12 and 24 months after insertion of the prosthesis, no complications were reported. Stereophotogrammetric technology is a viable, accurate and easy technique for making multiple implant impressions. Clinicians can use stereophotogrammetric technology to acquire reliable digital master models as a first step in producing frameworks with a correct passive fit.

Linguine sign at MR imaging: does it represent the collapsed silicone implant shell?

PubMed

Gorczyca, D P; DeBruhl, N D; Mund, D F; Bassett, L W

1994-05-01

One intact and one ruptured single-lumen implant were surgically placed in a rabbit. Magnetic resonance (MR) imaging was performed before and after surgical removal, and the ruptured implant was imaged after removal of the implant shell. Multiple curvilinear hypointense lines (linguine sign) were present in the MR images of the ruptured implant and of the implant shell alone immersed in saline solution but not in the image of the free silicone. The collapsed implant shell in a ruptured silicone implant does cause the linguine sign.

BrachyView: multiple seed position reconstruction and comparison with CT post-implant dosimetry

NASA Astrophysics Data System (ADS)

Alnaghy, S.; Loo, K. J.; Cutajar, D. L.; Jalayer, M.; Tenconi, C.; Favoino, M.; Rietti, R.; Tartaglia, M.; Carriero, F.; Safavi-Naeini, M.; Bucci, J.; Jakubek, J.; Pospisil, S.; Zaider, M.; Lerch, M. L. F.; Rosenfeld, A. B.; Petasecca, M.

2016-05-01

BrachyView is a novel in-body imaging system utilising high-resolution pixelated silicon detectors (Timepix) and a pinhole collimator for brachytherapy source localisation. Recent studies have investigated various options for real-time intraoperative dynamic dose treatment planning to increase the quality of implants. In a previous proof-of-concept study, the justification of the pinhole concept was shown, allowing for the next step whereby multiple active seeds are implanted into a PMMA phantom to simulate a more realistic clinical scenario. In this study, 20 seeds were implanted and imaged using a lead pinhole of 400 μ m diameter. BrachyView was able to resolve the seed positions within 1-2 mm of expected positions, which was verified by co-registering with a full clinical post-implant CT scan.

Microelectrode-based technology for the detection of low levels of bacteria

NASA Technical Reports Server (NTRS)

Rogers, Tom D.; Hitchens, G. D.; Mishra, S. K.; Pierson, D. L.

1992-01-01

A microelectrode-based electrochemical detection method was used for quantitation of bacteria in water samples. The redox mediator, benzoquinone, was used to accept electrons from the bacterial metabolic pathway to create a flow of electrons by reducing the mediator. Electrochemical monitoring electrodes detected the reduced mediator as it diffused out of the cells and produced a small electrical current. By using a combination of microelectrodes and monitoring instrumentation, the cumulative current generated by a particular bacterial population could be monitored. Using commercially available components, an electrochemical detection system was assembled and tested to evaluate its potential as an emerging technology for rapid detection and quantitation of bacteria in water samples.

The study and application of four kinds of organic ion-selective microsensors

NASA Astrophysics Data System (ADS)

Yu, Bi; Zheng, Xiao; Feng, Chu; Hong, Wen-Bing; Liu, Jun-Tao; Wang, Ru-Jiang

1991-09-01

Four kinds of organic ion-selective microelectrodes (two barrels, tip diameter 0.1-0.5 micron) have been developed for the measurement of acetylcholine, histamine, serotonin, and bile acid. Physiological and pathological models on the cellular or sub-cellular level have been established for the purpose of basic and clinical pharmacological research, treatment or diagnosis of certain diseases. The acetylcholine sensitive microelectrode has been applied to the study of acetylcholine activity in single erythrocytes of normal human subjects and patients suffering from manic depressive disorders. The bile acid selective microelectrode has been used for the direct measurement of intracellular bile acid activities both in colorectal cancer and colorectal mucosa in living condition.

A Simple and Low-Cost Ultramicroelectrode Fabrication and Characterization Method for Undergraduate Students

ERIC Educational Resources Information Center

Sur, Ujjal Kumar; Dhason, A.; Lakshminarayanan, V.

2012-01-01

A laboratory experiment is described in which students fabricate disk-shaped gold and platinum microelectrodes with diameters of 10-50 [mu]m by sealing sodalime glass with metal microwires. The electrodes are characterized by performing cyclic voltammetry in aqueous and acetonitrile solution. Commercial microelectrodes are expensive (cost depends…

Selective wetting-induced micro-electrode patterning for flexible micro-supercapacitors.

PubMed

Kim, Sung-Kon; Koo, Hyung-Jun; Lee, Aeri; Braun, Paul V

2014-08-13

Selective wetting-induced micro-electrode patterning is used to fabricate flexible micro-supercapacitors (mSCs). The resulting mSCs exhibit high performance, mechanical stability, stable cycle life, and hold great promise for facile integration into flexible devices requiring on-chip energy storage. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Further Evaluation of DNT Hazard Screening using Neural Networks from Rat Cortical Neurons on Multi-well Microelectrode Arrays

EPA Science Inventory

Thousands of chemicals have not been characterized for their DNT potential. Due to the need for DNT hazard identification, efforts to develop screening assays for DNT potential is a high priority. Multi-well microelectrode arrays (MEA) measure the spontaneous activity of electr...

Boron-doped diamond nano/microelectrodes for biosensing and in vitro measurements.

PubMed

Dong, Hua; Wang, Shihua; Galligan, James J; Swain, Greg M

2011-01-01

Since the fabrication of the first diamond electrode in the mid 1980s, repid progress has been made on the development and application of this new type of electrode material. Boron-doped diamond (BDD) electrodes exhibit outstanding properties compared to oxygen-containing sp2 carbon electrodes. These properties make BDD electrodes an ideal choice for use in complex samples. In recent years, BDD microelectrodes have been applied to in vitro measurements of biological molecules in tissues and cells. This review will summarize recent progress in the development and applications of BDD electrodes in bio-sensing and in vitro measurements of biomolecules. In the first section, the methods for BDD diamond film deposition and BDD microelectrodes preparation are described. This is followed by a description and discussion of several approaches for characterization of the BDD electrode surface structure, morphology, and electrochemical activity. Further, application of BDD microelectrodes for use in the in vitro analysis of norepinephrine (NE), serotonin (5-HT), nitric oxide (NO), histamine, and adenosine from tissues are summarized and finally some of the remaining challenges are discussed.

Boron-doped diamond nano/microelectrodes for bio-sensing and in vitro measurements

PubMed Central

Dong, Hua; Wang, Shihua; Galligan, James J.; Swain, Greg M.

2015-01-01

Since the fabrication of the first diamond electrode in the mid 1980s, repid progress has been made on the development and application of this new type of electrode material. Boron-doped diamond (BDD) electrodes exhibit outstanding properties compared to oxygen-containing sp2 carbon electrodes. These properties make BDD electrodes an ideal choice for use in complex samples. In recent years, BDD microelectrodes have been applied to in vitro and in vivo measurements of biological molecules in animals, tissues and cells. This review will summarize recent progress in the development and applications of BDD electrodes in bio-sensing and in vitro measurements of biomolecules. In the first section, the methods for BDD nanocrystalline diamond film deposition and BDD microelectrodes preparation are described. This is followed by a description and discussion of several approaches for characterization of the BDD electrode surface structure, morphology, and electrochemical activity. Further, application of BDD microelectrodes for use in the in vitro analysis of norepinephrine (NE), serotonin (5-HT), nitric oxide (NO), histamine, and adenosine from tissues are summarized and finally some of the remaining challenges are discussed. PMID:21196394

Electrochemical Evaluations of Fractal Microelectrodes for Energy Efficient Neurostimulation.

PubMed

Park, Hyunsu; Takmakov, Pavel; Lee, Hyowon

2018-03-12

Advancements in microfabrication has enabled manufacturing of microscopic neurostimulation electrodes with smaller footprint than ever possible. The smaller electrodes can potentially reduce tissue damage and allow better spatial resolution for neural stimulation. Although electrodes of any shape can easily be fabricated, substantial effort have been focused on identification and characterization of new materials and surface morphology for efficient charge injection, while maintaining simple circular or rectangular Euclidean electrode geometries. In this work we provide a systematic electrochemical evaluation of charge injection capacities of serpentine and fractal-shaped platinum microelectrodes and compare their performance with traditional circular microelectrodes. Our findings indicate that the increase in electrode perimeter leads to an increase in maximum charge injection capacity. Furthermore, we found that the electrode geometry can have even more significant impact on electrode performance than having a larger perimeter for a given surface area. The fractal-shaped microelectrodes, despite having smaller perimeter than other designs, demonstrated superior charge injection capacity. Our results suggest that electrode design can significantly affect both Faradaic and non-Faradaic electrochemical processes, which may be optimized to enable a more energy efficient design for neurostimulation.

Nanostructured gold microelectrodes for SERS and EIS measurements by incorporating ZnO nanorod growth with electroplating

PubMed Central

Zong, Xianli; Zhu, Rong; Guo, Xiaoliang

2015-01-01

In this paper, a fine gold nanostructure synthesized on selective planar microelectrodes in micro-chip is realized by using an advanced hybrid fabrication approach incorporating growth of nanorods (NRs) with gold electroplating. By this developed nanostructure, integration of in-situ surface-enhanced Raman spectroscopy (SERS) detection with electrochemical impedance spectroscopy (EIS) measurement for label-free, nondestructive, real-time and rapid monitoring on a single cell has been achieved. Moreover, parameters of Au nanostructures such as size of nanoholes/nanogaps can be controllably adjusted in the fabrication. We have demonstrated a SERS enhancement factor of up to ~2.24 × 106 and double-layer impedance decrease ratio of 90% ~ 95% at low frequency range below 200 kHz by using nanostructured microelectrodes. SERS detection and in-situ EIS measurement of a trapped single cell by using planar microelectrodes are realized to demonstrate the compatibility, multi-functions, high-sensitivity and simplicity of the micro-chip system. This dual function platform integrating SERS and EIS is of great significance in biological, biochemical and biomedical applications. PMID:26558325

Droplet electric separator microfluidic device for cell sorting

NASA Astrophysics Data System (ADS)

Guo, Feng; Ji, Xing-Hu; Liu, Kan; He, Rong-Xiang; Zhao, Li-Bo; Guo, Zhi-Xiao; Liu, Wei; Guo, Shi-Shang; Zhao, Xing-Zhong

2010-05-01

A simple and effective droplet electric separator microfluidic device was developed for cell sorting. The aqueous droplet without precharging operation was influenced to move a distance in the channel along the electric field direction by applying dc voltage on the electrodes beside the channel, which made the target droplet flowing to the collector. Single droplet can be isolated in a sorting rate of ˜100 Hz with microelectrodes under a required pulse. Single or multiple mammalian cell (HePG2) encapsulated in the surfactant free alginate droplet could be sorted out respectively. This method may be used for single cell operation or analysis.

Disseminated Pleural Siliconoma Mimicking Malignant Pleural Mesothelioma.

PubMed

Tanaka, Toshiki; Tao, Hiroyuki; Hayashi, Tatsuro; Yoshiyama, Koichi; Furukawa, Masashi; Yoshida, Kumiko; Okabe, Kazunori

2015-12-01

A 48-year-old woman with a 3-month history of back pain was admitted for further examination of multiple left pleural nodules. She had undergone bilateral breast augmentation with silicone implants 10 years previously. Nine years after the operation, both ruptured implants were removed, and autologous fat was injected. Computed tomography revealed multiple pleural nodules suggestive of malignant pleural mesothelioma. Thoracoscopic exploration revealed multiple pleural nodules with massive pleural adhesions. The nodules were filled with viscous liquid and were histologically determined to be siliconomas. Disseminated pleural siliconoma should be recognized as a late adverse event of silicone breast implantation. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Is The Real In Vivo Nitric Oxide Concentration Pico or Nano Molar? Influence of Electrode Size on Unstirred Layers and NO Consumption

PubMed Central

Bohlen, H. Glenn

2012-01-01

Objective There is a debate if the nitric oxide concentration ([NO]) required to influence vascular smooth muscle is below 50 nM or much higher. 30 μm and larger diameter electrodes report [NO] below 50 nM, whereas diameters of < 10–12 μm report hundreds of nM. This study examined how size of electrodes influenced [NO] measurement due to NO consumption and unstirred layer issues. Methods Electrodes were 2 mm disk, 30μm X 2 mm carbon fiber, and single 7μm diameter carbon fiber within open tip microelectrode, and exposed 7 μm carbon fiber of ~15 μm to 2 mm length. Results All electrodes demonstrated linear calibrations with sufficient stirring. As stirring slowed, 30 μm and 2 mm electrodes reported much lower [NO] due to unstirred layers and high NO consumption. The three 7 μm microelectrodes had minor stirring issues. With limited stirring with NO present, 7 μm open tip microelectrodes advanced toward 30 μm and 2 mm electrodes experienced dramatically decreased current within 10–50μm of the larger electrodes due to high NO consumption. None of the 7 μm microelectrodes interacted. Conclusions The data indicate large electrodes underestimate [NO] due to excessive NO consumption under conditions where unstirred layers are unavoidable and true microelectrodes are required for valid measurements. PMID:22925222

Electrochemical layer-by-layer approach to fabricate mechanically stable platinum black microelectrodes using a mussel-inspired polydopamine adhesive.

PubMed

Kim, Raeyoung; Nam, Yoonkey

2015-04-01

Platinum black (PtBK) has long been used for microelectrode fabrication owing to its high recording performance of neural signals. The porous structure of PtBK enlarges the surface area and lowers the impedance, which results in background noise reduction. However, the brittleness of PtBK has been a problem in practice. In this work, we report mechanically stable PtBK microelectrodes using a bioinspired adhesive film, polydopamine (pDA), while maintaining the low impedance of PtBK. The pDA layer was incorporated into the PtBK structure through electrochemical layer-by-layer deposition. Varying the number of layers and the order of materials, multi-layered pDA-PtBK hybrids were fabricated and the electrical properties, both impedance and charge injection limit, were evaluated. Multilayered pDA-PtBK hybrids had electrical impedances as low as PtBK controls and charge injection limit twice larger than controls. For the 30 min-ultrasonication agitation test, impedance levels rarely changed for some of the pDA-PtBK hybrids indicating that the pDA improved the mechanical property of the PtBK structures. The pDA-PtBK hybrid microelectrodes readily recorded neural signals of cultured hippocampal neurons, where background noise levels and signal-to-noise were 2.43 ∼ 3.23 μVrms and 28.4 ∼ 69.1, respectively. The developed pDA-PtBK hybrid microelectrodes are expected to be applicable to neural sensors for neural prosthetic studies.

Fully integrated three-dimensional electrodes for electrochemical detection in microchips: fabrication, characterization, and applications.

PubMed

Pai, Rekha S; Walsh, Kevin M; Crain, Mark M; Roussel, Thomas J; Jackson, Douglas J; Baldwin, Richard P; Keynton, Robert S; Naber, John F

2009-06-15

A scalable and rather inexpensive solution to producing microanalytical systems with "on-chip" three-dimensional (3D) microelectrodes is presented in this study, along with applicability to practical electrochemical (EC) detection scenarios such as preconcentration and interferant removal. This technique to create high-aspect-ratio (as much as 4:1) gold microstructures in constrained areas involved the modification of stud bump geometry with microfabricated silicon molds via an optimized combination of temperature, pressure, and time. The microelectrodes that resulted consisted of an array of square pillars approximately 18 microm tall and 20 microm wide on each side, placed at the end of a microfabricated electrophoresis channel. This technique increased the active surface area of the microelectrodes by as much as a factor of 50, while mass transfer and, consequently, preconcentration collection efficiencies were increased to approximately 100%, compared to approximately 30% efficiency for planar nonmodified microelectrodes (samples that were used included the neurotransmitters dopamine and catechol). The 3D microelectrodes were used both in a stand-alone configuration, for direct EC detection of model catecholamine analytes, and, more interestingly, in dual electrode configurations for EC sample processing prior to detection downstream at a second planar electrode. In particular, the 3D electrodes were shown to be capable of performing coulometry or complete (100%) redox conversion of analyte species over a wide range of concentrations, from 4.3 microM to 4.4 mM, in either plug-flow or continuous-flow formats.

Carbon nanospikes grown on metal wires as microelectrode sensors for dopamine

DOE PAGES

Zestos, Alexander G.; Yang, Cheng; Jacobs, Christopher B.; ...

2015-09-14

Carbon nanomaterials are advantageous as electrodes for neurotransmitter detection, but the difficulty of nanomaterials deposition on electrode substrates limits the reproducibility and future applications. In our study, we used plasma enhanced chemical vapor deposition (PECVD) to directly grow a thin layer of carbon nanospikes (CNS) on cylindrical metal substrates. No catalyst is required and the CNS surface coverage is uniform over the cylindrical metal substrate. We characterized the CNS growth on several metallic substrates including tantalum, niobium, palladium, and nickel wires. Using fast-scan cyclic voltammetry (FSCV), bare metal wires could not detect 1 mu M dopamine while carbon nanospike coatedmore » wires could. Moreover, the highest sensitivity and optimized S/N ratio was recorded from carbon nanospike-tantalum (CNS-Ta) microwires grown for 7.5 minutes, which had a LOD of 8 +/- 2 nM for dopamine with FSCV. CNS-Ta microelectrodes were more reversible and had a smaller Delta E-p for dopamine than carbon-fiber microelectrodes, suggesting faster electron transfer kinetics. The kinetics of dopamine redox were adsorption controlled at CNS-Ta microelectrodes and repeated electrochemical measurements displayed stability for up to ten hours in vitro and over a ten day period as well. The oxidation potential was significantly different for ascorbic acid and uric acid compared to dopamine. Finally, growing carbon nanospikes on metal wires is a promising method to produce uniformly-coated, carbon nanostructured cylindrical microelectrodes for sensitive dopamine detection.« less

Biomimetic Sensors for the Senses: Towards Better Understanding of Taste and Odor Sensation.

PubMed

Wu, Chunsheng; Du, Ya-Wen; Huang, Liquan; Ben-Shoshan Galeczki, Yaron; Dagan-Wiener, Ayana; Naim, Michael; Niv, Masha Y; Wang, Ping

2017-12-11

Taste and smell are very important chemical senses that provide indispensable information on food quality, potential mates and potential danger. In recent decades, much progress has been achieved regarding the underlying molecular and cellular mechanisms of taste and odor senses. Recently, biosensors have been developed for detecting odorants and tastants as well as for studying ligand-receptor interactions. This review summarizes the currently available biosensing approaches, which can be classified into two main categories: in vitro and in vivo approaches. The former is based on utilizing biological components such as taste and olfactory tissues, cells and receptors, as sensitive elements. The latter is dependent on signals recorded from animals' signaling pathways using implanted microelectrodes into living animals. Advantages and disadvantages of these two approaches, as well as differences in terms of sensing principles and applications are highlighted. The main current challenges, future trends and prospects of research in biomimetic taste and odor sensors are discussed.

Biomimetic Sensors for the Senses: Towards Better Understanding of Taste and Odor Sensation

PubMed Central

Wu, Chunsheng; Du, Ya-Wen; Huang, Liquan; Ben-Shoshan Galeczki, Yaron; Dagan-Wiener, Ayana; Naim, Michael; Wang, Ping

2017-01-01

Taste and smell are very important chemical senses that provide indispensable information on food quality, potential mates and potential danger. In recent decades, much progress has been achieved regarding the underlying molecular and cellular mechanisms of taste and odor senses. Recently, biosensors have been developed for detecting odorants and tastants as well as for studying ligand-receptor interactions. This review summarizes the currently available biosensing approaches, which can be classified into two main categories: in vitro and in vivo approaches. The former is based on utilizing biological components such as taste and olfactory tissues, cells and receptors, as sensitive elements. The latter is dependent on signals recorded from animals’ signaling pathways using implanted microelectrodes into living animals. Advantages and disadvantages of these two approaches, as well as differences in terms of sensing principles and applications are highlighted. The main current challenges, future trends and prospects of research in biomimetic taste and odor sensors are discussed. PMID:29232897

Development of closed-loop neural interface technology in a rat model: combining motor cortex operant conditioning with visual cortex microstimulation.

PubMed

Marzullo, Timothy Charles; Lehmkuhle, Mark J; Gage, Gregory J; Kipke, Daryl R

2010-04-01

Closed-loop neural interface technology that combines neural ensemble decoding with simultaneous electrical microstimulation feedback is hypothesized to improve deep brain stimulation techniques, neuromotor prosthetic applications, and epilepsy treatment. Here we describe our iterative results in a rat model of a sensory and motor neurophysiological feedback control system. Three rats were chronically implanted with microelectrode arrays in both the motor and visual cortices. The rats were subsequently trained over a period of weeks to modulate their motor cortex ensemble unit activity upon delivery of intra-cortical microstimulation (ICMS) of the visual cortex in order to receive a food reward. Rats were given continuous feedback via visual cortex ICMS during the response periods that was representative of the motor cortex ensemble dynamics. Analysis revealed that the feedback provided the animals with indicators of the behavioral trials. At the hardware level, this preparation provides a tractable test model for improving the technology of closed-loop neural devices.

A soft, transparent, freely accessible cranial window for chronic imaging and electrophysiology

PubMed Central

Heo, Chaejeong; Park, Hyejin; Kim, Yong-Tae; Baeg, Eunha; Kim, Yong Ho; Kim, Seong-Gi; Suh, Minah

2016-01-01

Chronic in vivo imaging and electrophysiology are important for better understanding of neural functions and circuits. We introduce the new cranial window using soft, penetrable, elastic, and transparent, silicone-based polydimethylsiloxane (PDMS) as a substitute for the skull and dura in both rats and mice. The PDMS can be readily tailored to any size and shape to cover large brain area. Clear and healthy cortical vasculatures were observed up to 15 weeks post-implantation. Real-time hemodynamic responses were successfully monitored during sensory stimulation. Furthermore, the PDMS window allowed for easy insertion of microelectrodes and micropipettes into the cortical tissue for electrophysiological recording and chemical injection at any location without causing any fluid leakage. Longitudinal two-photon microscopic imaging of Cx3Cr1+/− GFP transgenic mice was comparable with imaging via a conventional glass-type cranial window, even immediately following direct intracortical injection. This cranial window will facilitate direct probing and mapping for long-term brain studies. PMID:27283875

Neuroprosthetic limb control with electrocorticography: approaches and challenges.

PubMed

Thakor, Nitish V; Fifer, Matthew S; Hotson, Guy; Benz, Heather L; Newman, Geoffrey I; Milsap, Griffin W; Crone, Nathan E

2014-01-01

Advanced upper limb prosthetics, such as the Johns Hopkins Applied Physics Lab Modular Prosthetic Limb (MPL), are now available for research and preliminary clinical applications. Research attention has shifted to developing means of controlling these prostheses. Penetrating microelectrode arrays are often used in animal and human models to decode action potentials for cortical control. These arrays may suffer signal loss over the long-term and therefore should not be the only implant type investigated for chronic BMI use. Electrocorticographic (ECoG) signals from electrodes on the cortical surface may provide more stable long-term recordings. Several studies have demonstrated ECoG's potential for decoding cortical activity. As a result, clinical studies are investigating ECoG encoding of limb movement, as well as its use for interfacing with and controlling advanced prosthetic arms. This overview presents the technical state of the art in the use of ECoG in controlling prostheses. Technical limitations of the current approach and future directions are also presented.

Characterization of ToxCast Phase II compounds disruption of spontaneous network activity in cortical networks grown on multi-well microelectrode array (mwMEA) plates.

EPA Science Inventory

The development of multi-well microelectrode array (mwMEA) systems has increased in vitro screening throughput making them an effective method to screen and prioritize large sets of compounds for potential neurotoxicity. In the present experiments, a multiplexed approach was used...

Fabrication of small complex-shaped optics by plasma chemical vaporization machining with a microelectrode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takino, Hideo; Shibata, Norio; Itoh, Hiroshi

2006-08-10

We have developed plasma chemical vaporization machining by using a microelectrode for the fabrication of small complex-shaped optical surfaces. In this method, a0.5 mm diameter pipe microelectrode, from which processing gas is drawn in, generates a small localized plasma that is scanned over a work piece under numerical computer control to shape a desired surface. A12 mmx12 mm nonaxisymmetric mirror with a maximum depth of approximately 3 {mu}m was successfully fabricated with a peak-to-valley shape accuracy of 0.04 {mu}m in an area excluding the edges of the mirror. The average surface roughness was 0.58 nm, which is smooth enough formore » optical use.« less

[Flexible print circuit technology application in biomedical engineering].

PubMed

Jiang, Lihua; Cao, Yi; Zheng, Xiaolin

2013-06-01

Flexible print circuit (FPC) technology has been widely applied in variety of electric circuits with high precision due to its advantages, such as low-cost, high specific fabrication ability, and good flexibility, etc. Recently, this technology has also been used in biomedical engineering, especially in the development of microfluidic chip and microelectrode array. The high specific fabrication can help making microelectrode and other micro-structure equipment. And good flexibility allows the micro devices based on FPC technique to be easily packaged with other parts. In addition, it also reduces the damage of microelectrodes to the tissue. In this paper, the application of FPC technology in biomedical engineering is introduced. Moreover, the important parameters of FPC technique and the development trend of prosperous applications is also discussed.

Rigid spine reinforced polymer microelectrode array probe and method of fabrication

DOEpatents

Tabada, Phillipe; Pannu, Satinderpall S

2014-05-27

A rigid spine-reinforced microelectrode array probe and fabrication method. The probe includes a flexible elongated probe body with conductive lines enclosed within a polymeric material. The conductive lines connect microelectrodes found near an insertion end of the probe to respective leads at a connector end of the probe. The probe also includes a rigid spine, such as made from titanium, fixedly attached to the probe body to structurally reinforce the probe body and enable the typically flexible probe body to penetrate and be inserted into tissue, such as neural tissue. By attaching or otherwise fabricating the rigid spine to connect to only an insertion section of the probe body, an integrally connected cable section of the probe body may remain flexible.

Mathematical evaluation of the influence of multiple factors on implant stability quotient values in clinical practice: a retrospective study

PubMed Central

Huang, Hairong; Wismeijer, Daniel; Shao, Xianhong; Wu, Gang

2016-01-01

Objectives The objective of this study is to mathematically evaluate the influence of multiple factors on implant stability quotient values in clinical practice. Patients and methods Resonance frequency analysis was performed at T1 (measured immediately at the time of implant placement) and at T2 (measured before dental restoration) in 177 patients (329 implants). Using a multivariate linear regression model, we analyzed the influence of the following eleven candidate factors: sex, age, maxillary/mandibular location, bone type, immediate/delayed implantation, bone grafting (presence or absence), insertion torque, I-/II-stage healing pattern, implant diameter, implant length, and T1–T2 time interval. Results The following factors were identified to significantly influence the implant stability quotient (ISQ) values at T1: insertion torque, bone grafting, I-/II-stage healing pattern, immediate/delayed implantation, maxillary/mandibular location, implant diameter, and sex. In contrast, the ISQ values at T2 were significantly influenced only by three factors: implant diameter, T1–T2 time interval, and insertion torque. Conclusion Among the eleven candidate factors, seven key factors were found to influence the T1-ISQ values, while only three key factors influenced the T2-ISQ values. Both T1 and T2-ISQ values were found to be influenced by implant diameter and insertion torque. T1 was influenced specifically by the sex of the patient, the location (maxillary or mandibular), the implantation mode (immediate/delayed implantation), the healing stage, and the absence or presence of bone graft materials. PMID:27785040

Electrochemical layer-by-layer approach to fabricate mechanically stable platinum black microelectrodes using a mussel-inspired polydopamine adhesive

NASA Astrophysics Data System (ADS)

Kim, Raeyoung; Nam, Yoonkey

2015-04-01

Objective. Platinum black (PtBK) has long been used for microelectrode fabrication owing to its high recording performance of neural signals. The porous structure of PtBK enlarges the surface area and lowers the impedance, which results in background noise reduction. However, the brittleness of PtBK has been a problem in practice. In this work, we report mechanically stable PtBK microelectrodes using a bioinspired adhesive film, polydopamine (pDA), while maintaining the low impedance of PtBK. Approach. The pDA layer was incorporated into the PtBK structure through electrochemical layer-by-layer deposition. Varying the number of layers and the order of materials, multi-layered pDA-PtBK hybrids were fabricated and the electrical properties, both impedance and charge injection limit, were evaluated. Main results. Multilayered pDA-PtBK hybrids had electrical impedances as low as PtBK controls and charge injection limit twice larger than controls. For the 30 min-ultrasonication agitation test, impedance levels rarely changed for some of the pDA-PtBK hybrids indicating that the pDA improved the mechanical property of the PtBK structures. The pDA-PtBK hybrid microelectrodes readily recorded neural signals of cultured hippocampal neurons, where background noise levels and signal-to-noise were 2.43 ∼ 3.23 μVrms and 28.4 ∼ 69.1, respectively. Significance. The developed pDA-PtBK hybrid microelectrodes are expected to be applicable to neural sensors for neural prosthetic studies.

Double-barreled and Concentric Microelectrodes for Measurement of Extracellular Ion Signals in Brain Tissue

PubMed Central

Haack, Nicole; Durry, Simone; Kafitz, Karl W.; Chesler, Mitchell; Rose, Christine R.

2015-01-01

Electrical activity in the brain is accompanied by significant ion fluxes across membranes, resulting in complex changes in the extracellular concentration of all major ions. As these ion shifts bear significant functional consequences, their quantitative determination is often required to understand the function and dysfunction of neural networks under physiological and pathophysiological conditions. In the present study, we demonstrate the fabrication and calibration of double-barreled ion-selective microelectrodes, which have proven to be excellent tools for such measurements in brain tissue. Moreover, so-called “concentric” ion-selective microelectrodes are also described, which, based on their different design, offer a far better temporal resolution of fast ion changes. We then show how these electrodes can be employed in acute brain slice preparations of the mouse hippocampus. Using double-barreled, potassium-selective microelectrodes, changes in the extracellular potassium concentration ([K+]o) in response to exogenous application of glutamate receptor agonists or during epileptiform activity are demonstrated. Furthermore, we illustrate the response characteristics of sodium-sensitive, double-barreled and concentric electrodes and compare their detection of changes in the extracellular sodium concentration ([Na+]o) evoked by bath or pressure application of drugs. These measurements show that while response amplitudes are similar, the concentric sodium microelectrodes display a superior signal-to-noise ratio and response time as compared to the double-barreled design. Generally, the demonstrated procedures will be easily transferable to measurement of other ions species, including pH or calcium, and will also be applicable to other preparations. PMID:26381747

Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex

PubMed Central

Romanski, L. M.; Tian, B.; Fritz, J.; Mishkin, M.; Goldman-Rakic, P. S.; Rauschecker, J. P.

2009-01-01

‘What’ and ‘where’ visual streams define ventrolateral object and dorsolateral spatial processing domains in the prefrontal cortex of nonhuman primates. We looked for similar streams for auditory–prefrontal connections in rhesus macaques by combining microelectrode recording with anatomical tract-tracing. Injection of multiple tracers into physiologically mapped regions AL, ML and CL of the auditory belt cortex revealed that anterior belt cortex was reciprocally connected with the frontal pole (area 10), rostral principal sulcus (area 46) and ventral prefrontal regions (areas 12 and 45), whereas the caudal belt was mainly connected with the caudal principal sulcus (area 46) and frontal eye fields (area 8a). Thus separate auditory streams originate in caudal and rostral auditory cortex and target spatial and non-spatial domains of the frontal lobe, respectively. PMID:10570492

Screening the ToxCast Phase II library for acute neurotoxicity using cortical neurons grown on multi-well microelectrode array (mwMEA) plates

EPA Science Inventory

We have used primary cortical neurons grown in multi-well microelectrode array (mwMEA) plates to screen the ToxCast Phase II library of 1055 unique compounds for the ability to cause acute neurotoxicity. Each compound was screened at a single high concentration of 40 µM...

Robust Functionalization of Large Microelectrode Arrays by Using Pulsed Potentiostatic Deposition

PubMed Central

Rothe, Joerg; Frey, Olivier; Madangopal, Rajtarun; Rickus, Jenna; Hierlemann, Andreas

2016-01-01

Surface modification of microelectrodes is a central step in the development of microsensors and microsensor arrays. Here, we present an electrodeposition scheme based on voltage pulses. Key features of this method are uniformity in the deposited electrode coatings, flexibility in the overall deposition area, i.e., the sizes and number of the electrodes to be coated, and precise control of the surface texture. Deposition and characterization of four different materials are demonstrated, including layers of high-surface-area platinum, gold, conducting polymer poly(ethylenedioxythiophene), also known as PEDOT, and the non-conducting polymer poly(phenylenediamine), also known as PPD. The depositions were conducted using a fully integrated complementary metal-oxide-semiconductor (CMOS) chip with an array of 1024 microelectrodes. The pulsed potentiostatic deposition scheme is particularly suitable for functionalization of individual electrodes or electrode subsets of large integrated microelectrode arrays: the required deposition waveforms are readily available in an integrated system, the same deposition parameters can be used to functionalize the surface of either single electrodes or large arrays of thousands of electrodes, and the deposition method proved to be robust and reproducible for all materials tested. PMID:28025569

Carbon-Fiber Microelectrodes for In Vivo Applications

PubMed Central

Huffman, Megan L.; Venton, B. Jill

2009-01-01

Carbon-fiber microelectrodes (CFMEs) have been a useful tool for measuring rapid changes in neurotransmitters because of their small size, sensitivity, and good electrochemical properties. In this article, we highlight recent advances using CFMEs for measuring neurotransmitters in vivo. Dopamine has been a primary neurotransmitter of interest but direct electrochemical detection of other neurochemicals including nitric oxide and adenosine has also been investigated. Surface treatments have been studied to enhance electrode sensitivity, such as covalent modification or the addition of a layer of carbon nanotubes. Enzyme-modified microelectrodes that detect non-electroactive compounds further extend the usefulness of CFMEs beyond the traditional monoamines. CFMEs continue to be used in vivo to understand basic neurobiological mechanisms and the actions of pharmacological agents, including drugs of abuse. Advances in sensitivity and instrumentation now allow CFMEs to be used for measurements of natural dopamine release that occur during behavioral experiments. A new technique combining electrochemistry with electrophysiology at a single microelectrode facilitates a better understanding of neurotransmitter concentrations and their effects on cell firing. Future research in this field will likely concentrate on fabricating smaller electrodes and electrode arrays, as well as expanding the use of CFMEs in neuroscience beyond dopamine. PMID:19082168

Effects of osmolarity on human epithelial conjunctival cells using an electrical technique.

PubMed

Bellotti, Mariela; Bast, Walter; Berra, Alejandro; Bonetto, Fabian J

2011-12-01

The purpose of this study is to report the effect of different media osmolarity on a cell line monolayer of normal human conjunctival epithelia (IOBA-NHC) using Electric Cell-substrate Impedance Sensing (ECIS). We built our own ECIS system. We fabricated biocompatible microelectrodes. We used a monolayer of IOBA-NHC cells with media at different osmolarities (315, 360, 446, and 617 mOsm/l). When there is an increase in hyperosmolarity, there is a slight decrease in the measured resistance of the naked microelectrode (without cells), whereas its capacitance remained practically unchanged. The evaluation of resistance and capacitance of a microelectrode covered by a monolayer of IOBA-NHC in relation to a naked microelectrode showed no difference in the standard media (315 mOsm/l), a small difference with 360 mOsm/l, and significant differences with hyperosmolarities of 446 mOsm/l and 610 mOsm/l. The resistance with a confluent cell monolayer is up to three times greater compared to the value of the resistance of the naked electrode with standard media. Both resistance and capacitance measurements for the cell monolayer were sensitive to changes in osmolarity.

Influence of droplet coverage on the electrochemical response of planar microelectrodes and potential solving strategies based on nesting concept

PubMed Central

Yu, Yue

2016-01-01

Recently, biosensors have been widely used for the detection of bacteria, viruses and other toxins. Electrodes, as commonly used transducers, are a vital part of electrochemical biosensors. The coverage of the droplets can change significantly based on the hydrophobicity of the microelectrode surface materials. In the present research, screen-printed interdigitated microelectrodes (SPIMs), as one type of planar microelectrode, were applied to investigate the influence of droplet coverage on electrochemical response. Furthermore, three dimensional (3D) printing technology was employed to print smart devices with different diameters based on the nesting concept. Theoretical explanations were proposed to elucidate the influence of the droplet coverage on the electrochemical response. 3D-printed ring devices were used to incubate the SPIMs and the analytical performances of the SPIMs were tested. According to the results obtained, our device successfully improved the stability of the signal responses and eliminated irregular signal changes to a large extent. Our proposed method based on the nesting concept provides a promising method for the fabrication of stable electrochemical biosensors. We also introduced two types of electrode bases to improve the signal stability. PMID:27635356

Exploiting spatial degrees of freedom for high data rate ultrasound communication with implantable devices

NASA Astrophysics Data System (ADS)

Wang, Max L.; Arbabian, Amin

2017-09-01

We propose and demonstrate an ultrasonic communication link using spatial degrees of freedom to increase data rates for deeply implantable medical devices. Low attenuation and millimeter wavelengths make ultrasound an ideal communication medium for miniaturized low-power implants. While a small spectral bandwidth has drastically limited achievable data rates in conventional ultrasonic implants, a large spatial bandwidth can be exploited by using multiple transducers in a multiple-input/multiple-output system to provide spatial multiplexing gain without additional power, larger bandwidth, or complicated packaging. We experimentally verify the communication link in mineral oil with a transmitter and a receiver 5 cm apart, each housing two custom-designed mm-sized piezoelectric transducers operating at the same frequency. Two streams of data modulated with quadrature phase-shift keying at 125 kbps are simultaneously transmitted and received on both channels, effectively doubling the data rate to 250 kbps with a measured bit error rate below 10-4. We also evaluate the performance and robustness of the channel separation network by testing the communication link after introducing position offsets. These results demonstrate the potential of spatial multiplexing to enable more complex implant applications requiring higher data rates.

High-density CMOS Microelectrode Array System for Impedance Spectroscopy and Imaging of Biological Cells.

PubMed

Vijay, Viswam; Raziyeh, Bounik; Amir, Shadmani; Jelena, Dragas; Alicia, Boos Julia; Axel, Birchler; Jan, Müller; Yihui, Chen; Andreas, Hierlemann

2017-01-26

A monolithic measurement platform was implemented to enable label-free in-vitro electrical impedance spectroscopy measurements of cells on multi-functional CMOS microelectrode array. The array includes 59,760 platinum microelectrodes, densely packed within a 4.5 mm × 2.5 mm sensing region at a pitch of 13.5 μm. The 32 on-chip lock-in amplifiers can be used to measure the impedance of any arbitrarily chosen electrodes on the array by applying a sinusoidal voltage, generated by an on-chip waveform generator with a frequency range from 1 Hz to 1 MHz, and measuring the respective current. Proof-of-concept measurements of impedance sensing and imaging are shown in this paper. Correlations between cell detection through optical microscopy and electrochemical impedance scanning were established.

Electrochemical measurements on a droplet using gold microelectrodes

NASA Astrophysics Data System (ADS)

Jenabi, Amin; Souri, Asma; Rastkhadiv, Ali

2016-03-01

Facile methods of ion recognition are important for the fabrication of electronic tongue systems. In this work, we demonstrate performing pulsed conductometry on microliter electrolyte droplets dropped on gold microelectrodes vapor deposited on soda lime glass slides. A droplet is dropped between two microelectrodes when a voltage waveform from a preprogramed power supply is applied on them. The temporal variation of the electric current passing through the droplet is recorded, digitized and stored. The obtained data are compared with the database formed out of the previous experiences for the classification of the sample electrolytes. It is shown that the shape of the voltage waveform is the important parameter of the process. We devised a method for the optimization of the voltage waveform profile for obtaining the maximum of discriminating information from the recorded current variations.

Boron-doped diamond microdisc arrays: electrochemical characterisation and their use as a substrate for the production of microelectrode arrays of diverse metals (Ag, Au, Cu)via electrodeposition.

PubMed

Simm, Andrew O; Banks, Craig E; Ward-Jones, Sarah; Davies, Trevor J; Lawrence, Nathan S; Jones, Timothy G J; Jiang, Li; Compton, Richard G

2005-09-01

A novel boron-doped diamond (BDD) microelectrode array is characterised with electrochemical and atomic force microscopic techniques. The array consists of 40 micron-diameter sized BDD discs which are separated by 250 microns from their nearest neighbour in a hexagonal arrangement. The conducting discs can be electroplated to produce arrays of copper, silver or gold for analytical purposes in addition to operating as an array of BDD-microelectrodes. Proof-of-concept is shown for four separate examples; a gold plated array for arsenic detection, a copper plated array for nitrate analysis, a silver plated array for hydrogen peroxide monitoring and last, cathodic stripping voltammetry for lead at the bare BDD-array.

All-Electronic Quantification of Neuropeptide-Receptor Interaction Using a Bias-Free Functionalized Graphene Microelectrode.

PubMed

Ping, Jinglei; Vishnubhotla, Ramya; Xi, Jin; Ducos, Pedro; Saven, Jeffery G; Liu, Renyu; Johnson, Alan T Charlie

2018-05-22

Opioid neuropeptides play a significant role in pain perception, appetite regulation, sleep, memory, and learning. Advances in understanding of opioid peptide physiology are held back by the lack of methodologies for real-time quantification of affinities and kinetics of the opioid neuropeptide-receptor interaction at levels typical of endogenous secretion (<50 pM) in biosolutions with physiological ionic strength. To address this challenge, we developed all-electronic opioid-neuropeptide biosensors based on graphene microelectrodes functionalized with a computationally redesigned water-soluble μ-opioid receptor. We used the functionalized microelectrode in a bias-free charge measurement configuration to measure the binding kinetics and equilibrium binding properties of the engineered receptor with [d-Ala 2 , N-MePhe 4 , Gly-ol]-enkephalin and β-endorphin at picomolar levels in real time.

Towards real-time communication between in vivo neurophysiological data sources and simulator-based brain biomimetic models.

PubMed

Lee, Giljae; Matsunaga, Andréa; Dura-Bernal, Salvador; Zhang, Wenjie; Lytton, William W; Francis, Joseph T; Fortes, José Ab

2014-11-01

Development of more sophisticated implantable brain-machine interface (BMI) will require both interpretation of the neurophysiological data being measured and subsequent determination of signals to be delivered back to the brain. Computational models are the heart of the machine of BMI and therefore an essential tool in both of these processes. One approach is to utilize brain biomimetic models (BMMs) to develop and instantiate these algorithms. These then must be connected as hybrid systems in order to interface the BMM with in vivo data acquisition devices and prosthetic devices. The combined system then provides a test bed for neuroprosthetic rehabilitative solutions and medical devices for the repair and enhancement of damaged brain. We propose here a computer network-based design for this purpose, detailing its internal modules and data flows. We describe a prototype implementation of the design, enabling interaction between the Plexon Multichannel Acquisition Processor (MAP) server, a commercial tool to collect signals from microelectrodes implanted in a live subject and a BMM, a NEURON-based model of sensorimotor cortex capable of controlling a virtual arm. The prototype implementation supports an online mode for real-time simulations, as well as an offline mode for data analysis and simulations without real-time constraints, and provides binning operations to discretize continuous input to the BMM and filtering operations for dealing with noise. Evaluation demonstrated that the implementation successfully delivered monkey spiking activity to the BMM through LAN environments, respecting real-time constraints.

Neural correlates of behavioral amplitude modulation sensitivity in the budgerigar midbrain

PubMed Central

Neilans, Erikson G.; Abrams, Kristina S.; Idrobo, Fabio; Carney, Laurel H.

2016-01-01

Amplitude modulation (AM) is a crucial feature of many communication signals, including speech. Whereas average discharge rates in the auditory midbrain correlate with behavioral AM sensitivity in rabbits, the neural bases of AM sensitivity in species with human-like behavioral acuity are unexplored. Here, we used parallel behavioral and neurophysiological experiments to explore the neural (midbrain) bases of AM perception in an avian speech mimic, the budgerigar (Melopsittacus undulatus). Behavioral AM sensitivity was quantified using operant conditioning procedures. Neural AM sensitivity was studied using chronically implanted microelectrodes in awake, unrestrained birds. Average discharge rates of multiunit recording sites in the budgerigar midbrain were insufficient to explain behavioral sensitivity to modulation frequencies <100 Hz for both tone- and noise-carrier stimuli, even with optimal pooling of information across recording sites. Neural envelope synchrony, in contrast, could explain behavioral performance for both carrier types across the full range of modulation frequencies studied (16–512 Hz). The results suggest that envelope synchrony in the budgerigar midbrain may underlie behavioral sensitivity to AM. Behavioral AM sensitivity based on synchrony in the budgerigar, which contrasts with rate-correlated behavioral performance in rabbits, raises the possibility that envelope synchrony, rather than average discharge rate, might also underlie AM perception in other species with sensitive AM detection abilities, including humans. These results highlight the importance of synchrony coding of envelope structure in the inferior colliculus. Furthermore, they underscore potential benefits of devices (e.g., midbrain implants) that evoke robust neural synchrony. PMID:26843608

Bidirectional Telemetry Controller for Neuroprosthetic Devices

PubMed Central

Sharma, Vishnu; McCreery, Douglas B.; Han, Martin; Pikov, Victor

2010-01-01

We present versatile multifunctional programmable controller with bidirectional data telemetry, implemented using existing commercial microchips and standard Bluetooth protocol, which adds convenience, reliability, and ease-of-use to neuroprosthetic devices. Controller, weighing 190 g, is placed on animal's back and provides bidirectional sustained telemetry rate of 500 kb/s, allowing real-time control of stimulation parameters and viewing of acquired data. In continuously-active state, controller consumes ∼420 mW and operates without recharge for 8 h. It features independent 16-channel current-controlled stimulation, allowing current steering; customizable stimulus current waveforms; recording of stimulus voltage waveforms and evoked neuronal responses with stimulus artifact blanking circuitry. Flexibility, scalability, cost-efficiency, and a user-friendly computer interface of this device allow use in animal testing for variety of neuroprosthetic applications. Initial testing of the controller has been done in a feline model of brainstem auditory prosthesis. In this model, the electrical stimulation is applied to the array of microelectrodes implanted in the ventral cochlear nucleus, while the evoked neuronal activity was recorded with the electrode implanted in the contralateral inferior colliculus. Stimulus voltage waveforms to monitor the access impedance of the electrodes were acquired at the rate of 312 kilosamples/s. Evoked neuronal activity in the inferior colliculus was recorded after the blanking (transient silencing) of the recording amplifier during the stimulus pulse, allowing the detection of neuronal responses within 100 μs after the end of the stimulus pulse applied in the cochlear nucleus. PMID:19933010

Pyrrole-hyaluronic acid conjugates for decreasing cell binding to metals and conducting polymers

PubMed Central

Lee, Jae Young; Schmidt, Christine E.

2010-01-01

Surface modification of electrically conductive biomaterials has been studied to improve biocompatibility for a number of applications, such as implantable sensors and microelectrode arrays. In this study, we electrochemically coated electrodes with biocompatible and non-cell adhesive hyaluronic acid (HA) to reduce cellular adhesion for potential use in neural prostheses. To this end, pyrrole-conjugated hyaluronic acid (PyHA) was synthesized and employed for electrochemical coating of platinum, indium-tin-oxide, and polystyrene sulfonate-doped polypyrrole electrodes. This PyHA conjugate consists of (1) a pyrrole moiety that allows the compound to be electrochemically deposited onto a conductive substrate and (2) non-adhesive HA to minimize cell adhesion and to potentially decrease inflammatory tissue responses. Our characterization results showed the presence of a hydrophilic p(PyHA) layer on the modified electrode, and impedance measurements revealed impedance that was statistically the same as the unmodified electrode. We found that the p(PyHA)-coated electrodes minimized adhesion and migration of fibroblasts and astrocytes for a minimum of up to 3 months. Also, the coating was stable in physiological solution for 3 months and also stable against enzymatic degradation by hyaluronidase. These studies suggest that this p(PyHA)-coating has the potential to be used to mask conducting electrodes from adverse glial responses that occur upon implantation. In addition, electrochemical coating with PyHA can be potentially extended for the surface modification of other metallic and conducting substances such as stents and biosensors. PMID:20558330

Rodent model for assessing the long term safety and performance of peripheral nerve recording electrodes

NASA Astrophysics Data System (ADS)

Vasudevan, Srikanth; Patel, Kunal; Welle, Cristin

2017-02-01

Objective. In the US alone, there are approximately 185 000 cases of limb amputation annually, which can reduce the quality of life for those individuals. Current prosthesis technology could be improved by access to signals from the nervous system for intuitive prosthesis control. After amputation, residual peripheral nerves continue to convey motor signals and electrical stimulation of these nerves can elicit sensory percepts. However, current technology for extracting information directly from peripheral nerves has limited chronic reliability, and novel approaches must be vetted to ensure safe long-term use. The present study aims to optimize methods to establish a test platform using rodent model to assess the long term safety and performance of electrode interfaces implanted in the peripheral nerves. Approach. Floating Microelectrode Arrays (FMA, Microprobes for Life Sciences) were implanted into the rodent sciatic nerve. Weekly in vivo recordings and impedance measurements were performed in animals to assess performance and physical integrity of electrodes. Motor (walking track analysis) and sensory (Von Frey) function tests were used to assess change in nerve function due to the implant. Following the terminal recording session, the nerve was explanted and the health of axons, myelin and surrounding tissues were assessed using immunohistochemistry (IHC). The explanted electrodes were visualized under high magnification using scanning electrode microscopy (SEM) to observe any physical damage. Main results. Recordings of axonal action potentials demonstrated notable session-to-session variability. Impedance of the electrodes increased upon implantation and displayed relative stability until electrode failure. Initial deficits in motor function recovered by 2 weeks, while sensory deficits persisted through 6 weeks of assessment. The primary cause of failure was identified as lead wire breakage in all of animals. IHC indicated myelinated and unmyelinated axons near the implanted electrode shanks, along with dense cellular accumulations near the implant site. Scanning electron microscopy (SEM) showed alterations of the electrode insulation and deformation of electrode shanks. Significance. We describe a comprehensive testing platform with applicability to electrodes that record from the peripheral nerves. This study assesses the long term safety and performance of electrodes in the peripheral nerves using a rodent model. Under this animal test platform, FMA electrodes record single unit action potentials but have limited chronic reliability due to structural weaknesses. Future work will apply these methods to other commercially-available and novel peripheral electrode technologies. This research was carried out in the Division of Biomedical Physics, Office of Science and Engineering Laboratory, Center for Devices and Radiological Health, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.

Evaluation of the Neuroactivity of ToxCast Compounds Using Multi-well Microelectrode Array Recordings in Primary Cortical Neurons

EPA Science Inventory

Evaluation of the Neuroactivity of ToxCast Compounds Using Multi-well Microelectrode Array Recordings in Primary Cortical Neurons P Valdivia1, M Martin2, WR LeFew3, D Hall3, J Ross1, K Houck2 and TJ Shafer3 1Axion Biosystems, Atlanta GA and 2NCCT, 3ISTD, NHEERL, ORD, US EPA, RT...

Electrochemical sensor/detector system and method

DOEpatents

Glass, Robert S.; Perone, Sam P.; Ciarlo, Dino R.; Kimmons, James F.

1992-01-01

An electrochemical detection system is described comprising in combination: (a) a multielement, microelectrode array detector containing means for acquiring a plurality of signals; (b) electronic means for receiving said signals and converting said signals into a readout or display providing information with respect to the nature and concentration of elements present in a solution being tested. Also described is the means of making the above described microelectrode detector.

Electrochemical sensor/detector system and method

DOEpatents

Glass, Robert S.; Perone, Sam P.; Ciarlo, Dino R.; Kimmons, James F.

1994-01-01

An electrochemical detection system is described comprising in combination: (a) a multielement, microelectrode array detector containing means for acquiring a plurality of signals; (b) electronic means for receiving said signals and converting said signals into a readout or display providing information with respect to the nature and concentration of elements present in a solution being tested. Also described is the means of making the above described microelectrode detector.

Carbon Nanotube-based microelectrodes for enhanced detection of neurotransmitters

NASA Astrophysics Data System (ADS)

Jacobs, Christopher B.

Fast-scan cyclic voltammetry (FSCV) is one of the common techniques used for rapid measurement of neurotransmitters in vivo. Carbon-fiber microelectrodes (CFMEs) are typically used for neurotransmitter detection because of sub-second measurement capabilities, ability to measure changes in neurotransmitter concentration during neurotransmission, and the small size electrode diameter, which limits the amount of damage caused to tissue. Cylinder CFMEs, typically 50 -- 100 microm long, are commonly used for in vivo experiments because the electrode sensitivity is directly related to the electrode surface area. However the length of the electrode can limit the spatial resolution of neurotransmitter detection, which can restrict experiments in Drosophila and other small model systems. In addition, the electrode sensitivity toward dopamine and serotonin detection drops significantly for measurements at rates faster than 10 Hz, limiting the temporal resolution of CFMEs. While the use of FSCV at carbon-fiber microelectrodes has led to substantial strides in our understanding of neurotransmission, techniques that expand the capabilities of CFMEs are crucial to fully maximize the potential uses of FSCV. This dissertation introduces new methods to integrate carbon nanotubes (CNT) into microelectrodes and discusses the electrochemical enhancements of these CNT-microelectrodes. The electrodes are specifically designed with simple fabrication procedures so that highly specialized equipment is not necessary, and they utilize commercially available materials so that the electrodes could be easily integrated into existing systems. The electrochemical properties of CNT modified CFMEs are characterized using FSCV and the effect of CNT functionalization on these properties is explored in Chapter 2. For example, CFME modification using carboxylic acid functionalized CNTs yield about a 6-fold increase in dopamine oxidation current, but modification with octadecylamine CNTs results in a negligible change to the signal. Chapter 3 is devoted to the development and characterization of new CNT-Yarn Microelectrodes (CNTYME) which display a beneficial enhancement in sensitivity and reduction in both electron transfer kinetics and overpotential. Chapter 4 introduces the high-speed dopamine detection capabilities of CNTYMEs, almost two orders of magnitude faster than at CFMEs without any compromise in electrochemical sensitivity, and discusses how adsorption and desorption relate to this phenomenon.

Functionalization and characterization of pyrolyzed polymer based carbon microstructures for bionanoelectronics platforms

NASA Astrophysics Data System (ADS)

Hirabayashi, Mieko; Mehta, Beejal; Vahidi, Nasim W.; Khosla, Ajit; Kassegne, Sam

2013-11-01

In this study, the investigation of surface-treatment of chemically inert graphitic carbon microelectrodes (derived from pyrolyzed photoresist polymer) for improving their attachment chemistry with DNA molecular wires and ropes as part of a bionanoelectronics platform is reported. Polymer microelectrodes were fabricated on a silicon wafer using standard negative lithography procedures with negative-tone photoresist. These microelectrode structures were then pyrolyzed and converted to a form of conductive carbon that is referred to as PP (pyrolyzed polymer) carbon throughout this paper. Functionalization of the resulting pyrolyzed structures was done using nitric, sulfuric, 4-amino benzoic acids (4-ABA), and oxygen plasma etching and the surface modifications confirmed with Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, and electron dispersion x-ray spectroscopy (EDS). Post surface-treatment analysis of microelectrodes with FTIR and Raman spectroscopy showed signature peaks characteristics of carboxyl functional groups while EDS showed an increase in oxygen content in the surface-treatment procedures (except 4-ABA) indicating an increase in carboxyl functional group. These functional groups form the basis for peptide bond with aminated oligonucleotides that in turn could be used as molecular wires and interconnects in a bionanoelectronics platform. Post-pyrolysis analysis using EDS showed relatively higher oxygen concentrations at the edges and location of defects compared to other locations on these microelectrodes. In addition, electrochemical impedance measurements showed metal-like behavior of PP carbon with high conductivity (|Z| <1 KΩ) and no detectable detrimental effect of oxygen plasma surface-treatment on electrical characteristic. In general, characterization results—taken together—indicated that oxygen plasma surface-treatment produced more reliable, less damaging, and consistently repeatable generation of carboxyl functional groups than diazonium salt and strong acid treatments.

Enhanced electroanalysis in lithium potassium eutectic (LKE) using microfabricated square microelectrodes.

PubMed

Corrigan, Damion K; Blair, Ewen O; Terry, Jonathan G; Walton, Anthony J; Mount, Andrew R

2014-11-18

Molten salts (MSs) are an attractive medium for chemical and electrochemical processing and as a result there is demand for MS-compatible analysis technologies. However, MSs containing redox species present a challenging environment in which to perform analytical measurements because of their corrosive nature, significant thermal convection and the high temperatures involved. This paper outlines the fabrication and characterization of microfabricated square microelectrodes (MSMs) designed for electrochemical analysis in MS systems. Their design enables precise control over electrode dimension, the minimization of stress because of differential thermal expansion through design for high temperature operation, and the minimization of corrosive attack through effective insulation. The exemplar MS system used for characterization was lithium chloride/potassium chloride eutectic (LKE), which has potential applications in pyrochemical nuclear fuel reprocessing, metal refining, molten salt batteries and electric power cells. The observed responses for a range of redox ions between 400 and 500 °C (673 and 773 K) were quantitative and typical of microelectrodes. MSMs also showed the reduced iR drop, steady-state diffusion-limited response, and reduced sensitivity to convection seen for microelectrodes under ambient conditions and expected for these electrodes in comparison to macroelectrodes. Diffusion coefficients were obtained in close agreement with literature values, more readily and at greater precision and accuracy than both macroelectrode and previous microelectrode measurements. The feasibility of extracting individual physical parameters from mixtures of redox species (as required in reprocessing) and of the prolonged measurement required for online monitoring was also demonstrated. Together, this demonstrates that MSMs provide enhanced electrode devices widely applicable to the characterization of redox species in a range of MS systems.

A study of the dynamics of seizure propagation across micro domains in the vicinity of the seizure onset zone.

PubMed

Basu, Ishita; Kudela, Pawel; Korzeniewska, Anna; Franaszczuk, Piotr J; Anderson, William S

2015-08-01

The use of micro-electrode arrays to measure electrical activity from the surface of the brain is increasingly being investigated as a means to improve seizure onset zone (SOZ) localization. In this work, we used a multivariate autoregressive model to determine the evolution of seizure dynamics in the [Formula: see text] Hz high frequency band across micro-domains sampled by such micro-electrode arrays. We showed that a directed transfer function (DTF) can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with known propagation pattern. We used seven complex partial seizures recorded from four patients undergoing intracranial monitoring for surgical evaluation to reconstruct the seizure propagation pattern over sliding windows using a DTF measure. We showed that a DTF can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with a known propagation pattern. In general, depending on the location of the micro-electrode grid with respect to the clinical SOZ and the time from seizure onset, ictal propagation changed in directional characteristics over a 2-10 s time scale, with gross directionality limited to spatial dimensions of approximately [Formula: see text]. It was also seen that the strongest seizure patterns in the high frequency band and their sources over such micro-domains are more stable over time and across seizures bordering the clinically determined SOZ than inside. This type of propagation analysis might in future provide an additional tool to epileptologists for characterizing epileptogenic tissue. This will potentially help narrowing down resection zones without compromising essential brain functions as well as provide important information about targeting anti-epileptic stimulation devices.

A study of the dynamics of seizure propagation across micro domains in the vicinity of the seizure onset zone

NASA Astrophysics Data System (ADS)

Basu, Ishita; Kudela, Pawel; Korzeniewska, Anna; Franaszczuk, Piotr J.; Anderson, William S.

2015-08-01

Objective. The use of micro-electrode arrays to measure electrical activity from the surface of the brain is increasingly being investigated as a means to improve seizure onset zone (SOZ) localization. In this work, we used a multivariate autoregressive model to determine the evolution of seizure dynamics in the 70-110 Hz high frequency band across micro-domains sampled by such micro-electrode arrays. We showed that a directed transfer function (DTF) can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with known propagation pattern. Approach. We used seven complex partial seizures recorded from four patients undergoing intracranial monitoring for surgical evaluation to reconstruct the seizure propagation pattern over sliding windows using a DTF measure. Main results. We showed that a DTF can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with a known propagation pattern. In general, depending on the location of the micro-electrode grid with respect to the clinical SOZ and the time from seizure onset, ictal propagation changed in directional characteristics over a 2-10 s time scale, with gross directionality limited to spatial dimensions of approximately 9 m{{m}2}. It was also seen that the strongest seizure patterns in the high frequency band and their sources over such micro-domains are more stable over time and across seizures bordering the clinically determined SOZ than inside. Significance. This type of propagation analysis might in future provide an additional tool to epileptologists for characterizing epileptogenic tissue. This will potentially help narrowing down resection zones without compromising essential brain functions as well as provide important information about targeting anti-epileptic stimulation devices.

Covalent Immobilization of Enoxacin onto Titanium Implant Surfaces for Inhibiting Multiple Bacterial Species Infection and In Vivo Methicillin-Resistant Staphylococcus aureus Infection Prophylaxis

PubMed Central

Nie, Bin'en; Long, Teng; Ao, Haiyong; Zhou, Jianliang; Tang, Tingting

2016-01-01

ABSTRACT Infection is one of the most important causes of titanium implant failure in vivo. A developing prophylactic method involves the immobilization of antibiotics, especially vancomycin, onto the surface of the titanium implant. However, these methods have a limited effect in curbing multiple bacterial infections due to antibiotic specificity. In the current study, enoxacin was covalently bound to an amine-functionalized Ti surface by use of a polyethylene glycol (PEG) spacer, and the bactericidal effectiveness was investigated in vitro and in vivo. The titanium surface was amine functionalized with 3-aminopropyltriethoxysilane (APTES), through which PEG spacer molecules were covalently immobilized onto the titanium, and then the enoxacin was covalently bound to the PEG, which was confirmed by X-ray photoelectron spectrometry (XPS). A spread plate assay, confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM) were used to characterize the antimicrobial activity. For the in vivo study, Ti implants were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and implanted into the femoral medullary cavity of rats. The degree of infection was assessed by radiography, micro-computed tomography, and determination of the counts of adherent bacteria 3 weeks after surgery. Our data demonstrate that the enoxacin-modified PEGylated Ti surface effectively prevented bacterial colonization without compromising cell viability, adhesion, or proliferation in vitro. Furthermore, it prevented MRSA infection of the Ti implants in vivo. Taken together, our results demonstrate that the use of enoxacin-modified Ti is a potential approach to the alleviation of infections of Ti implants by multiple bacterial species. PMID:27799220

REVIEW OF SIGNAL DISTORTION THROUGH METAL MICROELECTRODE RECORDING CIRCUITS AND FILTERS

PubMed Central

NELSON, Matthew J.; POUGET, Pierre; NILSEN, Erik A.; PATTEN, Craig D.; SCHALL, Jeffrey D.

2008-01-01

Interest in local field potentials (LFPs) and action potential shape has increased markedly. The present work describes distortions of these signals that occur for two reasons. First, the microelectrode recording circuit operates as a voltage divider producing frequency-dependent attenuation and phase-shifts when electrode impedance is not negligible relative to amplifier input impedance. Because of the much higher electrode impedance at low frequencies, this occurred over frequency ranges of LFPs measured by neurophysiologists for one head-stage tested. Second, frequency-dependent phase shifts are induced by subsequent filters. Thus, we report these effects and the resulting amplitude envelope delays and distortion of waveforms recorded through a commercial data acquisition system and a range of tungsten microelectrodes. These distortions can be corrected, but must be accounted for when interpreting field potential and spike shape data. PMID:18242715

Solid-contact potentiometric polymer membrane microelectrodes for the detection of silver ions at the femtomole level

PubMed Central

Rubinova, Nastassia; Chumbimuni-Torres, Karin; Bakker, Eric

2010-01-01

In recent years, ion-selective electrodes based on polymer membranes have been shown to exhibit detection limits that are often in the nanomolar concentration range, and thus drastically lower than traditionally accepted. Since potentiometry is less dependent on scaling laws that other established analytical techniques, their performance in confined sample volumes is explored here. Solid-contact silver-selective microelectrodes, with a sodium-selective microelectrode as a reference, were inserted into a micropipette tip used as a 50-μl sample. The observed potential stabilities, reproducibilities and detection limits were attractive and largely matched that for large 100-ml samples. This should pave the way for further experiments to detecting ultra-small total ion concentrations by potentiometry, especially when used as a transducer after an amplification step in bioanalysis. PMID:20543910

Review of signal distortion through metal microelectrode recording circuits and filters.

PubMed

Nelson, Matthew J; Pouget, Pierre; Nilsen, Erik A; Patten, Craig D; Schall, Jeffrey D

2008-03-30

Interest in local field potentials (LFPs) and action potential shape has increased markedly. The present work describes distortions of these signals that occur for two reasons. First, the microelectrode recording circuit operates as a voltage divider producing frequency-dependent attenuation and phase shifts when electrode impedance is not negligible relative to amplifier input impedance. Because of the much higher electrode impedance at low frequencies, this occurred over frequency ranges of LFPs measured by neurophysiologists for one head-stage tested. Second, frequency-dependent phase shifts are induced by subsequent filters. Thus, we report these effects and the resulting amplitude envelope delays and distortion of waveforms recorded through a commercial data acquisition system and a range of tungsten microelectrodes. These distortions can be corrected, but must be accounted for when interpreting field potential and spike shape data.

Wireless Instantaneous Neurotransmitter Concentration System–based amperometric detection of dopamine, adenosine, and glutamate for intraoperative neurochemical monitoring

PubMed Central

Agnesi, Filippo; Tye, Susannah J.; Bledsoe, Jonathan M.; Griessenauer, Christoph J.; Kimble, Christopher J.; Sieck, Gary C.; Bennet, Kevin E.; Garris, Paul A.; Blaha, Charles D.; Lee, Kendall H.

2009-01-01

Object In a companion study, the authors describe the development of a new instrument named the Wireless Instantaneous Neurotransmitter Concentration System (WINCS), which couples digital telemetry with fast-scan cyclic voltammetry (FSCV) to measure extracellular concentrations of dopamine. In the present study, the authors describe the extended capability of the WINCS to use fixed potential amperometry (FPA) to measure extracellular concentrations of dopamine, as well as glutamate and adenosine. Compared with other electrochemical techniques such as FSCV or high-speed chronoamperometry, FPA offers superior temporal resolution and, in combination with enzyme-linked biosensors, the potential to monitor nonelectroactive analytes in real time. Methods The WINCS design incorporated a transimpedance amplifier with associated analog circuitry for FPA; a microprocessor; a Bluetooth transceiver; and a single, battery-powered, multilayer, printed circuit board. The WINCS was tested with 3 distinct recording electrodes: 1) a carbon-fiber microelectrode (CFM) to measure dopamine; 2) a glutamate oxidase enzyme-linked electrode to measure glutamate; and 3) a multiple enzyme-linked electrode (adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase) to measure adenosine. Proof-of-principle analyses included noise assessments and in vitro and in vivo measurements that were compared with similar analyses by using a commercial hardwired electrochemical system (EA161 Picostat, eDAQ; Pty Ltd). In urethane-anesthetized rats, dopamine release was monitored in the striatum following deep brain stimulation (DBS) of ascending dopaminergic fibers in the medial forebrain bundle (MFB). In separate rat experiments, DBS-evoked adenosine release was monitored in the ventrolateral thalamus. To test the WINCS in an operating room setting resembling human neurosurgery, cortical glutamate release in response to motor cortex stimulation (MCS) was monitored using a large-mammal animal model, the pig. Results The WINCS, which is designed in compliance with FDA-recognized consensus standards for medical electrical device safety, successfully measured dopamine, glutamate, and adenosine, both in vitro and in vivo. The WINCS detected striatal dopamine release at the implanted CFM during DBS of the MFB. The DBS-evoked adenosine release in the rat thalamus and MCS-evoked glutamate release in the pig cortex were also successfully measured. Overall, in vitro and in vivo testing demonstrated signals comparable to a commercial hardwired electrochemical system for FPA. Conclusions By incorporating FPA, the chemical repertoire of WINCS-measurable neurotransmitters is expanded to include glutamate and other nonelectroactive species for which the evolving field of enzyme-linked biosensors exists. Because many neurotransmitters are not electrochemically active, FPA in combination with enzyme-linked microelectrodes represents a powerful intraoperative tool for rapid and selective neurochemical sampling in important anatomical targets during functional neurosurgery. PMID:19425899

Wireless Instantaneous Neurotransmitter Concentration System-based amperometric detection of dopamine, adenosine, and glutamate for intraoperative neurochemical monitoring.

PubMed

Agnesi, Filippo; Tye, Susannah J; Bledsoe, Jonathan M; Griessenauer, Christoph J; Kimble, Christopher J; Sieck, Gary C; Bennet, Kevin E; Garris, Paul A; Blaha, Charles D; Lee, Kendall H

2009-10-01

In a companion study, the authors describe the development of a new instrument named the Wireless Instantaneous Neurotransmitter Concentration System (WINCS), which couples digital telemetry with fast-scan cyclic voltammetry (FSCV) to measure extracellular concentrations of dopamine. In the present study, the authors describe the extended capability of the WINCS to use fixed potential amperometry (FPA) to measure extracellular concentrations of dopamine, as well as glutamate and adenosine. Compared with other electrochemical techniques such as FSCV or high-speed chronoamperometry, FPA offers superior temporal resolution and, in combination with enzyme-linked biosensors, the potential to monitor nonelectroactive analytes in real time. The WINCS design incorporated a transimpedance amplifier with associated analog circuitry for FPA; a microprocessor; a Bluetooth transceiver; and a single, battery-powered, multilayer, printed circuit board. The WINCS was tested with 3 distinct recording electrodes: 1) a carbon-fiber microelectrode (CFM) to measure dopamine; 2) a glutamate oxidase enzyme-linked electrode to measure glutamate; and 3) a multiple enzyme-linked electrode (adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase) to measure adenosine. Proof-of-principle analyses included noise assessments and in vitro and in vivo measurements that were compared with similar analyses by using a commercial hardwired electrochemical system (EA161 Picostat, eDAQ; Pty Ltd). In urethane-anesthetized rats, dopamine release was monitored in the striatum following deep brain stimulation (DBS) of ascending dopaminergic fibers in the medial forebrain bundle (MFB). In separate rat experiments, DBS-evoked adenosine release was monitored in the ventrolateral thalamus. To test the WINCS in an operating room setting resembling human neurosurgery, cortical glutamate release in response to motor cortex stimulation (MCS) was monitored using a large-mammal animal model, the pig. The WINCS, which is designed in compliance with FDA-recognized consensus standards for medical electrical device safety, successfully measured dopamine, glutamate, and adenosine, both in vitro and in vivo. The WINCS detected striatal dopamine release at the implanted CFM during DBS of the MFB. The DBS-evoked adenosine release in the rat thalamus and MCS-evoked glutamate release in the pig cortex were also successfully measured. Overall, in vitro and in vivo testing demonstrated signals comparable to a commercial hardwired electrochemical system for FPA. By incorporating FPA, the chemical repertoire of WINCS-measurable neurotransmitters is expanded to include glutamate and other nonelectroactive species for which the evolving field of enzyme-linked biosensors exists. Because many neurotransmitters are not electrochemically active, FPA in combination with enzyme-linked microelectrodes represents a powerful intraoperative tool for rapid and selective neurochemical sampling in important anatomical targets during functional neurosurgery.

Predictive Modeling of Implantation Outcome in an In Vitro Fertilization Setting: An Application of Machine Learning Methods.

PubMed

Uyar, Asli; Bener, Ayse; Ciray, H Nadir

2015-08-01

Multiple embryo transfers in in vitro fertilization (IVF) treatment increase the number of successful pregnancies while elevating the risk of multiple gestations. IVF-associated multiple pregnancies exhibit significant financial, social, and medical implications. Clinicians need to decide the number of embryos to be transferred considering the tradeoff between successful outcomes and multiple pregnancies. To predict implantation outcome of individual embryos in an IVF cycle with the aim of providing decision support on the number of embryos transferred. Retrospective cohort study. Electronic health records of one of the largest IVF clinics in Turkey. The study data set included 2453 embryos transferred at day 2 or day 3 after intracytoplasmic sperm injection (ICSI). Each embryo was represented with 18 clinical features and a class label, +1 or -1, indicating positive and negative implantation outcomes, respectively. For each classifier tested, a model was developed using two-thirds of the data set, and prediction performance was evaluated on the remaining one-third of the samples using receiver operating characteristic (ROC) analysis. The training-testing procedure was repeated 10 times on randomly split (two-thirds to one-third) data. The relative predictive values of clinical input characteristics were assessed using information gain feature weighting and forward feature selection methods. The naïve Bayes model provided 80.4% accuracy, 63.7% sensitivity, and 17.6% false alarm rate in embryo-based implantation prediction. Multiple embryo implantations were predicted at a 63.8% sensitivity level. Predictions using the proposed model resulted in higher accuracy compared with expert judgment alone (on average, 75.7% and 60.1%, respectively). A machine learning-based decision support system would be useful in improving the success rates of IVF treatment. © The Author(s) 2014.

Direct Measurement of Intracellular Pressure

PubMed Central

Petrie, Ryan J.; Koo, Hyun

2014-01-01

A method to directly measure the intracellular pressure of adherent, migrating cells is described in the Basic Protocol. This approach is based on the servo-null method where a microelectrode is introduced into the cell to directly measure the physical pressure of the cytoplasm. We also describe the initial calibration of the microelectrode as well as the application of the method to cells migrating inside three-dimensional (3D) extracellular matrix (ECM). PMID:24894836

Static and Dynamic Measurement of Dopamine Adsorption in Carbon Fiber Microelectrodes Using Electrochemical Impedance Spectroscopy.

PubMed

Rivera-Serrano, Nilka; Pagan, Miraida; Colón-Rodríguez, Joanisse; Fuster, Christian; Vélez, Román; Almodovar-Faria, Jose; Jiménez-Rivera, Carlos; Cunci, Lisandro

2018-02-06

In this study, electrochemical impedance spectroscopy was used for the first time to study the adsorption of dopamine in carbon fiber microelectrodes. In order to show a proof-of-concept, static and dynamic measurements were taken at potentials ranging from -0.4 to 0.8 V versus Ag|AgCl to demonstrate the versatility of this technique to study dopamine without the need of its oxidation. We used electrochemical impedance spectroscopy and single frequency electrochemical impedance to measure different concentrations of dopamine as low as 1 nM. Moreover, the capacitance of the microelectrodes surface was found to decrease due to dopamine adsorption, which is dependent on its concentration. The effect of dissolved oxygen and electrochemical oxidation of the surface in the detection of dopamine was also studied. Nonoxidized and oxidized carbon fiber microelectrodes were prepared and characterized by optical microscopy, scanning electron microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. Optimum working parameters of the electrodes, such as frequency and voltage, were obtained for better measurement. Electrochemical impedance of dopamine was determined at different concentration, voltages, and frequencies. Finally, dynamic experiments were conducted using a flow cell and single frequency impedance in order to study continuous and real-time measurements of dopamine.

Field-programmable lab-on-a-chip based on microelectrode dot array architecture.

PubMed

Wang, Gary; Teng, Daniel; Lai, Yi-Tse; Lu, Yi-Wen; Ho, Yingchieh; Lee, Chen-Yi

2014-09-01

The fundamentals of electrowetting-on-dielectric (EWOD) digital microfluidics are very strong: advantageous capability in the manipulation of fluids, small test volumes, precise dynamic control and detection, and microscale systems. These advantages are very important for future biochip developments, but the development of EWOD microfluidics has been hindered by the absence of: integrated detector technology, standard commercial components, on-chip sample preparation, standard manufacturing technology and end-to-end system integration. A field-programmable lab-on-a-chip (FPLOC) system based on microelectrode dot array (MEDA) architecture is presented in this research. The MEDA architecture proposes a standard EWOD microfluidic component called 'microelectrode cell', which can be dynamically configured into microfluidic components to perform microfluidic operations of the biochip. A proof-of-concept prototype FPLOC, containing a 30 × 30 MEDA, was developed by using generic integrated circuits computer aided design tools, and it was manufactured with standard low-voltage complementary metal-oxide-semiconductor technology, which allows smooth on-chip integration of microfluidics and microelectronics. By integrating 900 droplet detection circuits into microelectrode cells, the FPLOC has achieved large-scale integration of microfluidics and microelectronics. Compared to the full-custom and bottom-up design methods, the FPLOC provides hierarchical top-down design approach, field-programmability and dynamic manipulations of droplets for advanced microfluidic operations.

Feasibility Study of Extended-Gate-Type Silicon Nanowire Field-Effect Transistors for Neural Recording

PubMed Central

Kang, Hongki; Kim, Jee-Yeon; Choi, Yang-Kyu; Nam, Yoonkey

2017-01-01

In this research, a high performance silicon nanowire field-effect transistor (transconductance as high as 34 µS and sensitivity as 84 nS/mV) is extensively studied and directly compared with planar passive microelectrode arrays for neural recording application. Electrical and electrochemical characteristics are carefully characterized in a very well-controlled manner. We especially focused on the signal amplification capability and intrinsic noise of the transistors. A neural recording system using both silicon nanowire field-effect transistor-based active-type microelectrode array and platinum black microelectrode-based passive-type microelectrode array are implemented and compared. An artificial neural spike signal is supplied as input to both arrays through a buffer solution and recorded simultaneously. Recorded signal intensity by the silicon nanowire transistor was precisely determined by an electrical characteristic of the transistor, transconductance. Signal-to-noise ratio was found to be strongly dependent upon the intrinsic 1/f noise of the silicon nanowire transistor. We found how signal strength is determined and how intrinsic noise of the transistor determines signal-to-noise ratio of the recorded neural signals. This study provides in-depth understanding of the overall neural recording mechanism using silicon nanowire transistors and solid design guideline for further improvement and development. PMID:28350370

Feasibility Study of Extended-Gate-Type Silicon Nanowire Field-Effect Transistors for Neural Recording.

PubMed

Kang, Hongki; Kim, Jee-Yeon; Choi, Yang-Kyu; Nam, Yoonkey

2017-03-28

In this research, a high performance silicon nanowire field-effect transistor (transconductance as high as 34 µS and sensitivity as 84 nS/mV) is extensively studied and directly compared with planar passive microelectrode arrays for neural recording application. Electrical and electrochemical characteristics are carefully characterized in a very well-controlled manner. We especially focused on the signal amplification capability and intrinsic noise of the transistors. A neural recording system using both silicon nanowire field-effect transistor-based active-type microelectrode array and platinum black microelectrode-based passive-type microelectrode array are implemented and compared. An artificial neural spike signal is supplied as input to both arrays through a buffer solution and recorded simultaneously. Recorded signal intensity by the silicon nanowire transistor was precisely determined by an electrical characteristic of the transistor, transconductance. Signal-to-noise ratio was found to be strongly dependent upon the intrinsic 1/f noise of the silicon nanowire transistor. We found how signal strength is determined and how intrinsic noise of the transistor determines signal-to-noise ratio of the recorded neural signals. This study provides in-depth understanding of the overall neural recording mechanism using silicon nanowire transistors and solid design guideline for further improvement and development.

Multiple ion beam irradiation for the study of radiation damage in materials

NASA Astrophysics Data System (ADS)

Taller, Stephen; Woodley, David; Getto, Elizabeth; Monterrosa, Anthony M.; Jiao, Zhijie; Toader, Ovidiu; Naab, Fabian; Kubley, Thomas; Dwaraknath, Shyam; Was, Gary S.

2017-12-01

The effects of transmutation produced helium and hydrogen must be included in ion irradiation experiments to emulate the microstructure of reactor irradiated materials. Descriptions of the criteria and systems necessary for multiple ion beam irradiation are presented and validated experimentally. A calculation methodology was developed to quantify the spatial distribution, implantation depth and amount of energy-degraded and implanted light ions when using a thin foil rotating energy degrader during multi-ion beam irradiation. A dual ion implantation using 1.34 MeV Fe+ ions and energy-degraded D+ ions was conducted on single crystal silicon to benchmark the dosimetry used for multi-ion beam irradiations. Secondary Ion Mass Spectroscopy (SIMS) analysis showed good agreement with calculations of the peak implantation depth and the total amount of iron and deuterium implanted. The results establish the capability to quantify the ion fluence from both heavy ion beams and energy-degraded light ion beams for the purpose of using multi-ion beam irradiations to emulate reactor irradiated microstructures.

Multivariate Autoregressive Modeling and Granger Causality Analysis of Multiple Spike Trains

PubMed Central

Krumin, Michael; Shoham, Shy

2010-01-01

Recent years have seen the emergence of microelectrode arrays and optical methods allowing simultaneous recording of spiking activity from populations of neurons in various parts of the nervous system. The analysis of multiple neural spike train data could benefit significantly from existing methods for multivariate time-series analysis which have proven to be very powerful in the modeling and analysis of continuous neural signals like EEG signals. However, those methods have not generally been well adapted to point processes. Here, we use our recent results on correlation distortions in multivariate Linear-Nonlinear-Poisson spiking neuron models to derive generalized Yule-Walker-type equations for fitting ‘‘hidden” Multivariate Autoregressive models. We use this new framework to perform Granger causality analysis in order to extract the directed information flow pattern in networks of simulated spiking neurons. We discuss the relative merits and limitations of the new method. PMID:20454705

A Multi-Functional Microelectrode Array Featuring 59760 Electrodes, 2048 Electrophysiology Channels, Stimulation, Impedance Measurement and Neurotransmitter Detection Channels.

PubMed

Dragas, Jelena; Viswam, Vijay; Shadmani, Amir; Chen, Yihui; Bounik, Raziyeh; Stettler, Alexander; Radivojevic, Milos; Geissler, Sydney; Obien, Marie; Müller, Jan; Hierlemann, Andreas

2017-06-01

Biological cells are characterized by highly complex phenomena and processes that are, to a great extent, interdependent. To gain detailed insights, devices designed to study cellular phenomena need to enable tracking and manipulation of multiple cell parameters in parallel; they have to provide high signal quality and high spatiotemporal resolution. To this end, we have developed a CMOS-based microelectrode array system that integrates six measurement and stimulation functions, the largest number to date. Moreover, the system features the largest active electrode array area to date (4.48×2.43 mm 2 ) to accommodate 59,760 electrodes, while its power consumption, noise characteristics, and spatial resolution (13.5 μm electrode pitch) are comparable to the best state-of-the-art devices. The system includes: 2,048 action-potential (AP, bandwidth: 300 Hz to 10 kHz) recording units, 32 local-field-potential (LFP, bandwidth: 1 Hz to 300 Hz) recording units, 32 current recording units, 32 impedance measurement units, and 28 neurotransmitter detection units, in addition to the 16 dual-mode voltage-only or current/voltage-controlled stimulation units. The electrode array architecture is based on a switch matrix, which allows for connecting any measurement/stimulation unit to any electrode in the array and for performing different measurement/stimulation functions in parallel.

To establish a pharmacological experimental platform for the study of cardiac hypoxia using the microelectrode array.

PubMed

Yeung, Chi-Kong; Sommerhage, Frank; Wrobel, Günter; Law, Jessica Ka-Yan; Offenhäusser, Andreas; Rudd, John Anthony; Ingebrandt, Sven; Chan, Mansun

2009-01-01

Simultaneous recording of electrical potentials from multiple cells may be useful for physiological and pharmacological research. The present study aimed to establish an in vitro cardiac hypoxia experimental platform on the microelectrode array (MEA). Embryonic rat cardiac myocytes were cultured on the MEAs. Following >or=90 min of hypoxia, changes in lactate production (mM), pH, beat frequency (beats per min, bpm), extracellular action potential (exAP) amplitude, and propagation velocity between the normoxic and hypoxic cells were compared. Under hypoxia, the beat frequency of cells increased and peaked at around 42.5 min (08.1+/-3.2 bpm). The exAP amplitude reduced as soon as the cells were exposed to the hypoxic medium, and this reduction increased significantly after approximately 20 min of hypoxia. The propagation velocity of the hypoxic cells was significantly lower than that of the control throughout the entire 90+ min of hypoxia. The rate of depolarisation and Na(+) signal gradually reduced over time, and these changes had a direct effect on the exAP duration. The extracellular electrophysiological measurements allow a partial reconstruction of the signal shape and time course of the underlying hypoxia-associated physiological changes. The present study showed that the cardiac myocyte-integrated MEA may be used as an experimental platform for the pharmacological studies of cardiovascular diseases in the future.

Cochlear Implantation for Children with Hearing Loss and Multiple Disabilities: An Evaluation from an Educator's Perspective

ERIC Educational Resources Information Center

Bertram, Bodo

2004-01-01

In recent years, parents of children with hearing loss and various additional disabilities have shown increasing interest in cochlear implants. This article describes how the program in Hanover, Germany is attempting to respond to this interest. It discusses the selection process for children who receive cochlear implants who have multiple…

Implants for orthodontic anchorage

PubMed Central

Zheng, Xiaowen; Sun, Yannan; Zhang, Yimei; Cai, Ting; Sun, Feng; Lin, Jiuxiang

2018-01-01

Abstract Implantanchorage continues to receive much attention as an important orthodontic anchorage. Since the development of orthodontic implants, the scope of applications has continued to increase. Although multiple reviews detailing implants have been published, no comprehensive evaluations have been performed. Thus, the purpose of this study was to comprehensively evaluate the effects of implants based on data published in review articles. An electronic search of the Cochrane Library, Medline, Embase, Ebsco and Sicencedirect for reviews with “orthodontic” and “systematic review or meta analysis” in the title, abstract, keywords, or full text was performed. A subsequent manual search was then performed to identify reviews concerning orthodontic implants. A manual search of the orthodontic journals American Journal of Orthodontics and Dentofacial Orthopedics (AJODO), European Journal of Orthodontics (EJO), and Angle Othodontist was also performed. Such systematic reviews that evaluated the efficacy and safety of orthodontic implants were used to indicate success rates and molar movements. A total of 23 reviews were included in the analysis. The quality of each review was assessed using a measurement tool for Assessment of Multiple Systematic Reviews (AMSTAR), and the review chosen to summarize outcomes had a quality score of >6. Most reviews were less than moderate quality. Success rates of implants ranged in a broad scope, and movement of the maxillary first molar was superior with implants compared with traditional anchorage. PMID:29595673

Microelectrode Geochemical Observatory for In Situ Monitoring of Metals Concentration and Mobility in Contaminated Sediments

DTIC Science & Technology

2013-09-01

SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON a. REPORT b. ABSTRACT c . THIS PAGE 19b. TELEPHONE...Report Microelectrode Geochemcial Observatory for In Situ Monitoring of Metals Concentration and Mobility in Contaminated Sediments N62583-11- C -0524...Representative Poor Electrochemical Scans APPENDIX B: Standard Solution Test Data APPENDIX C : Bremerton Porewater Test Data APPENDIX D: Porewater

Single and Multiple Microphone Noise Reduction Strategies in Cochlear Implants

PubMed Central

Azimi, Behnam; Hu, Yi; Friedland, David R.

2012-01-01

To restore hearing sensation, cochlear implants deliver electrical pulses to the auditory nerve by relying on sophisticated signal processing algorithms that convert acoustic inputs to electrical stimuli. Although individuals fitted with cochlear implants perform well in quiet, in the presence of background noise, the speech intelligibility of cochlear implant listeners is more susceptible to background noise than that of normal hearing listeners. Traditionally, to increase performance in noise, single-microphone noise reduction strategies have been used. More recently, a number of approaches have suggested that speech intelligibility in noise can be improved further by making use of two or more microphones, instead. Processing strategies based on multiple microphones can better exploit the spatial diversity of speech and noise because such strategies rely mostly on spatial information about the relative position of competing sound sources. In this article, we identify and elucidate the most significant theoretical aspects that underpin single- and multi-microphone noise reduction strategies for cochlear implants. More analytically, we focus on strategies of both types that have been shown to be promising for use in current-generation implant devices. We present data from past and more recent studies, and furthermore we outline the direction that future research in the area of noise reduction for cochlear implants could follow. PMID:22923425

New Methods for the Site-Selective Placement of Peptides on a Microelectrode Array: Probing VEGF-v107 Binding as Proof of Concept.

PubMed

Graaf, Matthew D; Marquez, Bernadette V; Yeh, Nai-Hua; Lapi, Suzanne E; Moeller, Kevin D

2016-10-21

Cu(I)-catalyzed "click" reactions cannot be performed on a borate ester derived polymer coating on a microelectrode array because the Cu(II) precursor for the catalyst triggers background reactions between both acetylene and azide groups with the polymer surface. Fortunately, the Cu(II)-background reaction can itself be used to site-selectively add the acetylene and azide nucleophiles to the surface of the array. In this way, molecules previously functionalized for use in "click" reactions can be added directly to the array. In a similar fashion, activated esters can be added site-selectively to a borate ester coated array. The new chemistry can be used to explore new biological interactions on the arrays. Specifically, the binding of a v107 derived peptide with both human and murine VEGF was probed using a functionalized microelectrode array.

Non-perturbative Quantification of Ionic Charge Transfer through Nm-Scale Protein Pores Using Graphene Microelectrodes

NASA Astrophysics Data System (ADS)

Ping, Jinglei; Johnson, A. T. Charlie; A. T. Charlie Johnson Team

Conventional electrical methods for detecting charge transfer through protein pores perturb the electrostatic condition of the solution and chemical reactivity of the pore, and are not suitable to be used for complex biofluids. We developed a non-perturbative methodology ( fW input power) for quantifying trans-pore electrical current and detecting the pore status (i.e., open vs. closes) via graphene microelectrodes. Ferritin was used as a model protein featuring a large interior compartment, well-separated from the exterior solution with discrete pores as charge commuting channels. The charge flowing through the ferritin pores transfers into the graphene microelectrode and is recorded by an electrometer. In this example, our methodology enables the quantification of an inorganic nanoparticle-protein nanopore interaction in complex biofluids. The authors acknowledge the support from the Defense Advanced Research Projects Agency (DARPA) and the U.S. Army Research Office under Grant Number W911NF1010093.

Electrochemical Visualization of Intracellular Hydrogen Peroxide at Single Cells.

PubMed

He, Ruiqin; Tang, Huifen; Jiang, Dechen; Chen, Hong-yuan

2016-02-16

In this Letter, the electrochemical visualization of hydrogen peroxide inside one cell was achieved first using a comprehensive Au-luminol-microelectrode and electrochemiluminescence. The capillary with a tip opening of 1-2 μm was filled with the mixture of chitosan and luminol, which was coated with the thin layers of polyvinyl chloride/nitrophenyloctyl ether (PVC/NPOE) and gold as the microelectrode. Upon contact with the aqueous hydrogen peroxide, hydrogen peroxide and luminol in contact with the gold layer were oxidized under the positive potential resulting in luminescence for the imaging. Due to the small diameter of the electrode, the microelectrode tip was inserted into one cell and the bright luminescence observed at the tip confirmed the visualization of intracellular hydrogen peroxide. The further coupling of oxidase on the electrode surface could open the field in the electrochemical imaging of intracellular biomolecules at single cells, which benefited the single cell electrochemical detection.

Impedance Characterization of the Degradation of Insulating Layer Patterned on Interdigitated Microelectrode.

PubMed

Lee, Gihyun; Kim, Sohee; Cho, Sungbo

2015-10-01

Life-time and functionality of planar microelectrode-based devices are determined by not only the corrosion-resistance of the electrode, but also the durability of the insulation layer coated on the transmission lines. Degradation of the insulating layer exposed to a humid environment or solution may cause leakage current or signal loss, and a decrease in measurement sensitivity. In this study, degradation of SU-8, an epoxy-based negative photoresist and insulating material, patterned on Au interdigitated microelectrode (IDE) for long-term (>30 days) immersion in an electrolyte at 37 °C was investigated by electrical impedance spectroscopy and theoretical equivalent circuit modeling. From the experiment and simulation results, it was found that the degradation level of the insulating layer of the IDE electrode can be characterized by monitoring the resistance of the insulating layer among the circuit parameters of the designed equivalent circuit modeling.

Monitoring Ion Activities In and Around Cells Using Ion-Selective Liquid-Membrane Microelectrodes

PubMed Central

Lee, Seong-Ki; Boron, Walter F.; Parker, Mark D.

2013-01-01

Determining the effective concentration (i.e., activity) of ions in and around living cells is important to our understanding of the contribution of those ions to cellular function. Moreover, monitoring changes in ion activities in and around cells is informative about the actions of the transporters and/or channels operating in the cell membrane. The activity of an ion can be measured using a glass microelectrode that includes in its tip a liquid-membrane doped with an ion-selective ionophore. Because these electrodes can be fabricated with tip diameters that are less than 1 μm, they can be used to impale single cells in order to monitor the activities of intracellular ions. This review summarizes the history, theory, and practice of ion-selective microelectrode use and brings together a number of classic and recent examples of their usefulness in the realm of physiological study. PMID:23322102

Performance sustaining intracortical neural prostheses

NASA Astrophysics Data System (ADS)

Nuyujukian, Paul; Kao, Jonathan C.; Fan, Joline M.; Stavisky, Sergey D.; Ryu, Stephen I.; Shenoy, Krishna V.

2014-12-01

Objective. Neural prostheses, or brain-machine interfaces, aim to restore efficient communication and movement ability to those suffering from paralysis. A major challenge these systems face is robust performance, particularly with aging signal sources. The aim in this study was to develop a neural prosthesis that could sustain high performance in spite of signal instability while still minimizing retraining time. Approach. We trained two rhesus macaques implanted with intracortical microelectrode arrays 1-4 years prior to this study to acquire targets with a neurally-controlled cursor. We measured their performance via achieved bitrate (bits per second, bps). This task was repeated over contiguous days to evaluate the sustained performance across time. Main results. We found that in the monkey with a younger (i.e., two year old) implant and better signal quality, a fixed decoder could sustain performance for a month at a rate of 4 bps, the highest achieved communication rate reported to date. This fixed decoder was evaluated across 22 months and experienced a performance decline at a rate of 0.24 bps yr-1. In the monkey with the older (i.e., 3.5 year old) implant and poorer signal quality, a fixed decoder could not sustain performance for more than a few days. Nevertheless, performance in this monkey was maintained for two weeks without requiring additional online retraining time by utilizing prior days’ experimental data. Upon analysis of the changes in channel tuning, we found that this stability appeared partially attributable to the cancelling-out of neural tuning fluctuations when projected to two-dimensional cursor movements. Significance. The findings in this study (1) document the highest-performing communication neural prosthesis in monkeys, (2) confirm and extend prior reports of the stability of fixed decoders, and (3) demonstrate a protocol for system stability under conditions where fixed decoders would otherwise fail. These improvements to decoder stability are important for minimizing training time and should make neural prostheses more practical to use.

A brain-spine interface alleviating gait deficits after spinal cord injury in primates.

PubMed

Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

2016-11-10

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.

A Brain–Spinal Interface Alleviating Gait Deficits after Spinal Cord Injury in Primates

PubMed Central

Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D.; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

2016-01-01

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain–computer interfaces1–3 have directly linked cortical activity to electrical stimulation of muscles, which have restored grasping abilities after hand paralysis1,4. Theoretically, this strategy could also restore control over leg muscle activity for walking5. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges6,7. Recently, we showed in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion8–10. Here, we interfaced leg motor cortex activity with epidural electrical stimulation protocols to establish a brain–spinal interface that alleviated gait deficits after a spinal cord injury in nonhuman primates. Rhesus monkeys were implanted with an intracortical microelectrode array into the leg area of motor cortex; and a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain–spinal interface in intact monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain–spinal interface restored weight-bearing locomotion of the paralyzed leg on a treadmill and overground. The implantable components integrated in the brain–spinal interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury. PMID:27830790

Predictors of serum chromium levels after stainless steel posterior spinal instrumentation for adolescent idiopathic scoliosis.

PubMed

Rackham, Matthew D; Cundy, Thomas P; Antoniou, Georgia; Freeman, Brian J C; Sutherland, Leanne M; Cundy, Peter J

2010-04-20

Prospective cohort study. To determine the predictors of serum chromium levels after stainless steel posterior spinal instrumentation for adolescent idiopathic scoliosis. Abnormally elevated serum chromium levels have been detected in patients with adolescent idiopathic scoliosis after stainless steel instrumentation. To date, the relationship among serum chromium levels, time of implantation, and implant characteristics (including surface area, rod length, numbers of hooks, screws, and cross connectors) has not been studied. Thirty patients with adolescent idiopathic scoliosis undergoing posterior instrumented spinal arthrodesis using stainless steel implants between 1998 and 2002 were prospectively studied. Serum chromium levels were measured between October 2006 and June 2007. Postoperative radiographs were used to measure rod lengths, number of hooks, screws, cross-connectors, and cables. The surface area of each component and the total surface area for each patient were calculated. Possible associations between serum chromium levels, time of implantation, and implant characteristics were investigated. Implant exposure, whether expressed in the form of total metal implant surface area, rod length, or number of metal interfaces, was found to be positively associated with serum chromium levels. Specifically, chromium levels increased by a multiplicative factor of 1.0060 for every additional square centimeter of total metal implant surface area (P = 0.02). In addition, the chromium level was found to decrease by a multiplicative factor of 0.7766 for every additional year since surgery (P = 0.02). After adjusting for the number of years since surgery, metal implant exposure is positively associated with elevated serum chromium levels in adolescent idiopathic scoliosis patients with stainless steel posterior spinal implants. This is the first study to identify statistically significant positive associations between specific spinal implant characteristics (other than corrosion identified by radiographs) and serum chromium levels.

Extraction of motor activity from the cervical spinal cord of behaving rats

NASA Astrophysics Data System (ADS)

Prasad, Abhishek; Sahin, Mesut

2006-12-01

Injury at the cervical region of the spinal cord results in the loss of the skeletal muscle control from below the shoulders and hence causes quadriplegia. The brain-computer interface technique is one way of generating a substitute for the lost command signals in these severely paralyzed individuals using the neural signals from the brain. In this study, we are investigating the feasibility of an alternative method where the volitional signals are extracted from the cervical spinal cord above the point of injury. A microelectrode array assembly was implanted chronically at the C5-C6 level of the spinal cord in rats. Neural recordings were made during the face cleaning behavior with forelimbs as this task involves cyclic forelimb movements and does not require any training. The correlation between the volitional motor signals and the elbow movements was studied. Linear regression technique was used to reconstruct the arm movement from the rectified-integrated version of the principal neural components. The results of this study demonstrate the feasibility of extracting the motor signals from the cervical spinal cord and using them for reconstruction of the elbow movements.

Correlations in V1 are reduced by stimulation outside the receptive field.

PubMed

Snyder, Adam C; Morais, Michael J; Kohn, Adam; Smith, Matthew A

2014-08-20

The trial-to-trial response variability of nearby cortical neurons is correlated. These correlations may strongly influence population coding performance. Numerous studies have shown that correlations can be dynamically modified by attention, adaptation, learning, and potent stimulus drive. However, the mechanisms that influence correlation strength remain poorly understood. Here we test whether correlations are influenced by presenting stimuli outside the classical receptive field (RF) of visual neurons, where they recruit a normalization signal termed surround suppression. We recorded simultaneously the activity of dozens of cells using microelectrode arrays implanted in the superficial layers of V1 in anesthetized, paralyzed macaque monkeys. We presented annular stimuli that encircled--but did not impinge upon--the RFs of the recorded cells. We found that these "extra-classical" stimuli reduced correlations in the absence of stimulation of the RF, closely resembling the decorrelating effects of stimulating the RFs directly. Our results suggest that normalization signals may be an important mechanism for modulating correlations. Copyright © 2014 the authors 0270-6474/14/3411222-06$15.00/0.

Automatic Training of Rat Cyborgs for Navigation.

PubMed

Yu, Yipeng; Wu, Zhaohui; Xu, Kedi; Gong, Yongyue; Zheng, Nenggan; Zheng, Xiaoxiang; Pan, Gang

2016-01-01

A rat cyborg system refers to a biological rat implanted with microelectrodes in its brain, via which the outer electrical stimuli can be delivered into the brain in vivo to control its behaviors. Rat cyborgs have various applications in emergency, such as search and rescue in disasters. Prior to a rat cyborg becoming controllable, a lot of effort is required to train it to adapt to the electrical stimuli. In this paper, we build a vision-based automatic training system for rat cyborgs to replace the time-consuming manual training procedure. A hierarchical framework is proposed to facilitate the colearning between rats and machines. In the framework, the behavioral states of a rat cyborg are visually sensed by a camera, a parameterized state machine is employed to model the training action transitions triggered by rat's behavioral states, and an adaptive adjustment policy is developed to adaptively adjust the stimulation intensity. The experimental results of three rat cyborgs prove the effectiveness of our system. To the best of our knowledge, this study is the first to tackle automatic training of animal cyborgs.

Automatic Training of Rat Cyborgs for Navigation

PubMed Central

Yu, Yipeng; Wu, Zhaohui; Xu, Kedi; Gong, Yongyue; Zheng, Nenggan; Zheng, Xiaoxiang; Pan, Gang

2016-01-01

A rat cyborg system refers to a biological rat implanted with microelectrodes in its brain, via which the outer electrical stimuli can be delivered into the brain in vivo to control its behaviors. Rat cyborgs have various applications in emergency, such as search and rescue in disasters. Prior to a rat cyborg becoming controllable, a lot of effort is required to train it to adapt to the electrical stimuli. In this paper, we build a vision-based automatic training system for rat cyborgs to replace the time-consuming manual training procedure. A hierarchical framework is proposed to facilitate the colearning between rats and machines. In the framework, the behavioral states of a rat cyborg are visually sensed by a camera, a parameterized state machine is employed to model the training action transitions triggered by rat's behavioral states, and an adaptive adjustment policy is developed to adaptively adjust the stimulation intensity. The experimental results of three rat cyborgs prove the effectiveness of our system. To the best of our knowledge, this study is the first to tackle automatic training of animal cyborgs. PMID:27436999

Hitchhiker's Guide to Voltammetry: Acute and Chronic Electrodes for in Vivo Fast-Scan Cyclic Voltammetry.

PubMed

Rodeberg, Nathan T; Sandberg, Stefan G; Johnson, Justin A; Phillips, Paul E M; Wightman, R Mark

2017-02-15

Fast-scan cyclic voltammetry (FSCV) has been used for over 20 years to study rapid neurotransmission in awake and behaving animals. These experiments were first carried out with carbon-fiber microelectrodes (CFMs) encased in borosilicate glass, which can be inserted into the brain through micromanipulators and guide cannulas. More recently, chronically implantable CFMs constructed with small diameter fused-silica have been introduced. These electrodes can be affixed in the brain with minimal tissue response, which permits longitudinal measurements of neurotransmission in single recording locations during behavior. Both electrode designs have been used to make novel discoveries in the fields of neurobiology, behavioral neuroscience, and psychopharmacology. The purpose of this Review is to address important considerations for the use of FSCV to study neurotransmitters in awake and behaving animals, with a focus on measurements of striatal dopamine. Common issues concerning experimental design, data collection, and calibration are addressed. When necessary, differences between the two methodologies (acute vs chronic recordings) are discussed. The topics raised in this Review are particularly important as the field moves beyond dopamine toward new neurochemicals and brain regions.

Self-expandable CoreValve implantation without contrast media.

PubMed

Bruschi, Giuseppe; Colombo, Paola; De Marco, Federico; Barosi, Alberto; Mauri, Silvia; Klugmann, Silvio

2016-09-01

Transcatheter aortic valve implantation has been designed to treat high-risk surgical patients affected by severe aortic stenosis, many of whom are affected by chronic kidney disease. To perform transcatheter self-expandable valve implantation, multiple contrast injections are required to monitor the procedure, so these patients are at increased risk of acute kidney injury. We described self-expandable transcatheter aortic valve implantation without contrast media in an 80-year-old man affected by severe aortic stenosis and endstage chronic kidney disease. © The Author(s) 2015.

Total artificial heart implantation in a young Marfan syndrome patient.

PubMed

Rao, Prashant; Keenan, Jack B; Rajab, Taufiek K; Kim, Samuel; Smith, Richard; Amabile, Orazio; Khalpey, Zain

2018-03-01

Cardiovascular complications represent the leading cause of morbidity and mortality in patients with Marfan syndrome. Here, we describe a unique case where a total artificial heart was implanted in a young Marfan syndrome woman. A 22-year-old postpartum African American female with Marfan syndrome developed multiple severe valve dysfunction and biventricular failure that was refractory to medical management. She previously had a Bentall procedure for Type A aortic dissection and repair of a Type B dissection. We implanted a total artificial heart with a good outcome. Total artificial heart is a durable option for severe biventricular failure and multiple valvular dysfunction as a bridge to transplant in a young patient with Marfan syndrome.

Accuracy and Reproducibility Using Patient-Specific Instrumentation in Total Ankle Arthroplasty.

PubMed

Daigre, Justin; Berlet, Gregory; Van Dyke, Bryan; Peterson, Kyle S; Santrock, Robert

2017-04-01

Implant survivorship is dependent on accuracy of implantation and successful soft tissue balancing. System instrumentation for total ankle arthroplasty implantation has a key influence on surgeon accuracy and reproducibility. The purpose of this study was to determine the accuracy and reproducibility of implant position with patient-specific guides for total ankle arthroplasty across multiple surgeons at multiple facilities. This retrospective, multicenter study included 44 patients who received a total ankle implant (INBONE II Total Ankle System; Wright Medical Technology, Memphis, TN) using PROPHECY patient-specific guides from January 2012 to December 2014. Forty-four patients with an average age of 63.0 years underwent total ankle arthroplasty using this preoperative patient-specific system. Preoperative computed tomography (CT) scans were obtained to assess coronal plane deformity, assess mechanical and anatomic alignment, and build patient-specific guides that referenced bony anatomy. The mean preoperative coronal deformity was 4.6 ± 4.6 degrees (range, 14 degrees varus to 17 degrees valgus). The first postoperative weightbearing radiographs were used to measure coronal and sagittal alignment of the implant vs the anatomic axis of the tibia. In 79.5% of patients, the postoperative implant position of the tibia corresponded to the preoperative plan of the tibia within 3 degrees of the intended target, within 4 degrees in 88.6% of patients, and within 5 degrees in 100% of patients. The tibial component coronal size was correctly predicted in 98% of cases, whereas the talar component was correctly predicted in 80% of cases. The use of patient-specific instrumentation for total ankle arthroplasty provided reliable alignment and reproducibility in the clinical situation similar to that shown in cadaveric testing. This study has shown that the preoperative patient-specific instrumentation provided for accuracy and reproducibility of ankle arthroplasty implantation in a cohort across multiple surgeons and facilities. Level III, retrospective comparative series.

Benefits of Localization and Speech Perception with Multiple Noise Sources in Listeners with a Short-electrode Cochlear Implant

PubMed Central

Dunn, Camille C.; Perreau, Ann; Gantz, Bruce; Tyler, Richard

2009-01-01

Background Research suggests that for individuals with significant low-frequency hearing, implantation of a short-electrode cochlear implant may provide benefits of improved speech perception abilities. Because this strategy combines acoustic and electrical hearing within the same ear while at the same time preserving low-frequency residual acoustic hearing in both ears, localization abilities may also be improved. However, very little research has focused on the localization and spatial hearing abilities of users with a short-electrode cochlear implant. Purpose The purpose of this study was to evaluate localization abilities for listeners with a short-electrode cochlear implant who continue to wear hearing aids in both ears. A secondary purpose was to document speech perception abilities using a speech in noise test with spatially-separate noise sources. Research Design Eleven subjects that utilized a short-electrode cochlear implant and bilateral hearing aids were tested on localization and speech perception with multiple noise locations using an eight-loudspeaker array. Performance was assessed across four listening conditions using various combinations of cochlear implant and/or hearing aid use. Results Results for localization showed no significant difference between using bilateral hearing aids and bilateral hearing aids plus the cochlear implant. However, there was a significant difference between the bilateral hearing aid condition and the implant plus use of a contralateral hearing aid for all eleven subjects. Results for speech perception showed a significant benefit when using bilateral hearing aids plus the cochlear implant over use of the implant plus only one hearing aid. Conclusion Combined use of both hearing aids and the cochlear implant show significant benefits for both localization and speech perception in noise for users with a short-electrode cochlear implant. These results emphasize the importance of low-frequency information in two ears for the purpose of localization and speech perception in noise. PMID:20085199

Benefits of localization and speech perception with multiple noise sources in listeners with a short-electrode cochlear implant.

PubMed

Dunn, Camille C; Perreau, Ann; Gantz, Bruce; Tyler, Richard S

2010-01-01

Research suggests that for individuals with significant low-frequency hearing, implantation of a short-electrode cochlear implant may provide benefits of improved speech perception abilities. Because this strategy combines acoustic and electrical hearing within the same ear while at the same time preserving low-frequency residual acoustic hearing in both ears, localization abilities may also be improved. However, very little research has focused on the localization and spatial hearing abilities of users with a short-electrode cochlear implant. The purpose of this study was to evaluate localization abilities for listeners with a short-electrode cochlear implant who continue to wear hearing aids in both ears. A secondary purpose was to document speech perception abilities using a speech-in-noise test with spatially separate noise sources. Eleven subjects that utilized a short-electrode cochlear implant and bilateral hearing aids were tested on localization and speech perception with multiple noise locations using an eight-loudspeaker array. Performance was assessed across four listening conditions using various combinations of cochlear implant and/or hearing aid use. Results for localization showed no significant difference between using bilateral hearing aids and bilateral hearing aids plus the cochlear implant. However, there was a significant difference between the bilateral hearing aid condition and the implant plus use of a contralateral hearing aid for all 11 subjects. Results for speech perception showed a significant benefit when using bilateral hearing aids plus the cochlear implant over use of the implant plus only one hearing aid. Combined use of both hearing aids and the cochlear implant show significant benefits for both localization and speech perception in noise for users with a short-electrode cochlear implant. These results emphasize the importance of low-frequency information in two ears for the purpose of localization and speech perception in noise.

Chemically Modified Microelectrode Arrays. New Kinds of Electronic Devices.

DTIC Science & Technology

1987-08-05

switching. Figure 1 shows a typical process for the fabrication of a microelectrode array consisting of eight, individually addressable Au (or Pt...S4r... -n - 2 ORGANIC CLEAN MRC SPUTTERING PHOTOLITHOGRAPHY _Suttred SI.N, & DRY ETCH _LorVO S1. 1.2 pm Figure 1. Flow chart for fabrication of...microelectrochemical devices, including polypyrrole, 14 poly(N-methylpyrrole), 14b poly(3-methylthiophene), 1 5 and polyaniline .15b,16 These materials can all be made by

Approaches to a cortical vision prosthesis: implications of electrode size and placement

NASA Astrophysics Data System (ADS)

Christie, Breanne P.; Ashmont, Kari R.; House, Paul A.; Greger, Bradley

2016-04-01

Objective. In order to move forward with the development of a cortical vision prosthesis, the critical issues in the field must be identified. Approach. To begin this process, we performed a brief review of several different cortical and retinal stimulation techniques that can be used to restore vision. Main results. Intracortical microelectrodes and epicortical macroelectrodes have been evaluated as the basis of a vision prosthesis. We concluded that an important knowledge gap necessitates an experimental in vivo performance evaluation of microelectrodes placed on the surface of the visual cortex. A comparison of the level of vision restored by intracortical versus epicortical microstimulation is necessary. Because foveal representation in the primary visual cortex involves more cortical columns per degree of visual field than does peripheral vision, restoration of foveal vision may require a large number of closely spaced microelectrodes. Based on previous studies of epicortical macrostimulation, it is possible that stimulation via surface microelectrodes could produce a lower spatial resolution, making them better suited for restoring peripheral vision. Significance. The validation of epicortical microstimulation in addition to the comparison of epicortical and intracortical approaches for vision restoration will fill an important knowledge gap and may have important implications for surgical strategies and device longevity. It is possible that the best approach to vision restoration will utilize both epicortical and intracortical microstimulation approaches, applying them appropriately to different visual representations in the primary visual cortex.

Novel microelectrode-based online system for monitoring N2O gas emissions during wastewater treatment.

PubMed

Marques, Ricardo; Oehmen, Adrian; Pijuan, Maite

2014-11-04

Clark-type nitrous oxide (N2O) microelectrodes are commonly used for measuring dissolved N2O levels, but have not previously been tested for gas-phase applications, where the N2O emitted from wastewater systems can be directly quantified. In this study, N2O microelectrodes were tested and validated for online gas measurements, and assessed with respect to their temperature, gas flow, composition dependence, gas pressure, and humidity. An exponential correlation between temperature and sensor signal was found, whereas gas flow, composition, pressure, and humidity did not have any influence on the signal. Two of the sensors were tested at different N2O concentration ranges (0-422.3, 0-50, 0-10, and 0-2 ppmv N2O) and exhibited a linear response over each range. The N2O emission dynamics from two laboratory scale sequencing batch reactors performing ammonia or nitrite oxidation were also monitored using one of the microsensors and results were compared with two other analytical methods. Results show that N2O emissions were accurately described with these microelectrodes and support their application for assessing gaseous N2O emissions from wastewater treatment systems. Advantages of the sensors as compared to conventional measurement techniques include a wider quantification range of N2O fluxes, and a single measurement system that can assess both liquid and gas-phase N2O dynamics.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zestos, Alexander G.; Yang, Cheng; Jacobs, Christopher B.

Carbon nanomaterials are advantageous as electrodes for neurotransmitter detection, but the difficulty of nanomaterials deposition on electrode substrates limits the reproducibility and future applications. In our study, we used plasma enhanced chemical vapor deposition (PECVD) to directly grow a thin layer of carbon nanospikes (CNS) on cylindrical metal substrates. No catalyst is required and the CNS surface coverage is uniform over the cylindrical metal substrate. We characterized the CNS growth on several metallic substrates including tantalum, niobium, palladium, and nickel wires. Using fast-scan cyclic voltammetry (FSCV), bare metal wires could not detect 1 mu M dopamine while carbon nanospike coatedmore » wires could. Moreover, the highest sensitivity and optimized S/N ratio was recorded from carbon nanospike-tantalum (CNS-Ta) microwires grown for 7.5 minutes, which had a LOD of 8 +/- 2 nM for dopamine with FSCV. CNS-Ta microelectrodes were more reversible and had a smaller Delta E-p for dopamine than carbon-fiber microelectrodes, suggesting faster electron transfer kinetics. The kinetics of dopamine redox were adsorption controlled at CNS-Ta microelectrodes and repeated electrochemical measurements displayed stability for up to ten hours in vitro and over a ten day period as well. The oxidation potential was significantly different for ascorbic acid and uric acid compared to dopamine. Finally, growing carbon nanospikes on metal wires is a promising method to produce uniformly-coated, carbon nanostructured cylindrical microelectrodes for sensitive dopamine detection.« less

Determination of subthalamic nucleus location by quantitative analysis of despiked background neural activity from microelectrode recordings obtained during deep brain stimulation surgery.

PubMed

Danish, Shabbar F; Baltuch, Gordon H; Jaggi, Jurg L; Wong, Stephen

2008-04-01

Microelectrode recording during deep brain stimulation surgery is a useful adjunct for subthalamic nucleus (STN) localization. We hypothesize that information in the nonspike background activity can help identify STN boundaries. We present results from a novel quantitative analysis that accomplishes this goal. Thirteen consecutive microelectrode recordings were retrospectively analyzed. Spikes were removed from the recordings with an automated algorithm. The remaining "despiked" signals were converted via root mean square amplitude and curve length calculations into "feature profile" time series. Subthalamic nucleus boundaries determined by inspection, based on sustained deviations from baseline for each feature profile, were compared against those determined intraoperatively by the clinical neurophysiologist. Feature profile activity within STN exhibited a sustained rise in 10 of 13 tracks (77%). The sensitivity of STN entry was 60% and 90% for curve length and root mean square amplitude, respectively, when agreement within 0.5 mm of the neurophysiologist's prediction was used. Sensitivities were 70% and 100% for 1 mm accuracy. Exit point sensitivities were 80% and 90% for both features within 0.5 mm and 1.0 mm, respectively. Reproducible activity patterns in deep brain stimulation microelectrode recordings can allow accurate identification of STN boundaries. Quantitative analyses of this type may provide useful adjunctive information for electrode placement in deep brain stimulation surgery.

Visualization of spiral ganglion neurites within the scala tympani with a cochlear implant in situ

PubMed Central

Chikar, Jennifer A.; Batts, Shelley A.; Pfingst, Bryan E.; Raphael, Yehoash

2009-01-01

Current cochlear histology methods do not allow in situ processing of cochlear implants. The metal components of the implant preclude standard embedding and mid-modiolar sectioning, and whole mounts do not have the spatial resolution needed to view the implant within the scala tympani. One focus of recent auditory research is the regeneration of structures within the cochlea, particularly the ganglion cells and their processes, and there are multiple potential benefits to cochlear implant users from this work. To facilitate experimental investigations of auditory nerve regeneration performed in conjunction with cochlear implantation, it is critical to visualize the cochlear tissue and the implant together to determine if the nerve has made contact with the implant. This paper presents a novel histological technique that enables simultaneous visualization of the in situ cochlear implant and neurofilament – labeled nerve processes within the scala tympani, and the spatial relationship between them. PMID:19428528

Visualization of spiral ganglion neurites within the scala tympani with a cochlear implant in situ.

PubMed

Chikar, Jennifer A; Batts, Shelley A; Pfingst, Bryan E; Raphael, Yehoash

2009-05-15

Current cochlear histology methods do not allow in situ processing of cochlear implants. The metal components of the implant preclude standard embedding and mid-modiolar sectioning, and whole mounts do not have the spatial resolution needed to view the implant within the scala tympani. One focus of recent auditory research is the regeneration of structures within the cochlea, particularly the ganglion cells and their processes, and there are multiple potential benefits to cochlear implant users from this work. To facilitate experimental investigations of auditory nerve regeneration performed in conjunction with cochlear implantation, it is critical to visualize the cochlear tissue and the implant together to determine if the nerve has made contact with the implant. This paper presents a novel histological technique that enables simultaneous visualization of the in situ cochlear implant and neurofilament-labeled nerve processes within the scala tympani, and the spatial relationship between them.

Distant Migration of Multiple Siliconomas in Lower Extremities following Breast Implant Rupture: Case Report.

PubMed

Oh, Joo Hyun; Song, Seung Yong; Lew, Dae Hyun; Lee, Dong Won

2016-10-01

Siliconoma from ruptured breast implants has been reported in multiple body sites, including but not limited to the breast parenchyma, axillary lymph nodes, upper arm, and even lower leg. In this regard, we report a rare case of distant silicone migration to the lower extremities after traumatic breast implant rupture. A 55-year-old Asian woman who received bilateral augmentation mammoplasty 20 years ago presented with ruptured breast implants from a car accident 2 years earlier. Magnetic resonance imaging confirmed intracapsular and extracapsular rupture of the right breast implant, showing "linguine sign." We removed the bilateral breast implants and performed capsulectomy and bilateral reduction mammoplasty using inverted-T incisions. The implant was confirmed as a smooth, silicone gel-filled mammary implant of 125 cm 3 by a Japanese manufacturer, Koken. During her regular follow-up outpatient visits, physical examination revealed 2.5- × 1.5-cm ill-defined, tender, subcutaneous nodules on both knees and 8.5- × 3.0-cm inflammatory changes in the inguinal area with persistent pain. Computed tomography showed no definite mass, but rather infiltrative, nonenhancing soft-tissue densities in the subcutaneous layers of the bilateral inguinal and knee areas. Surgical excision was performed, and pathologic findings confirmed variable vacuoles with foreign body reaction and fibrosis, consistent with siliconoma. It is important to acknowledge that siliconomas can be encountered in patients with ruptured breast implants, especially those manufactured decades ago. Our patient with masses as remote as the inguinal and knee areas is a prime example of how far siliconomas can migrate.

Distant Migration of Multiple Siliconomas in Lower Extremities following Breast Implant Rupture: Case Report

PubMed Central

Oh, Joo Hyun; Song, Seung Yong; Lew, Dae Hyun

2016-01-01

Summary: Siliconoma from ruptured breast implants has been reported in multiple body sites, including but not limited to the breast parenchyma, axillary lymph nodes, upper arm, and even lower leg. In this regard, we report a rare case of distant silicone migration to the lower extremities after traumatic breast implant rupture. A 55-year-old Asian woman who received bilateral augmentation mammoplasty 20 years ago presented with ruptured breast implants from a car accident 2 years earlier. Magnetic resonance imaging confirmed intracapsular and extracapsular rupture of the right breast implant, showing “linguine sign.” We removed the bilateral breast implants and performed capsulectomy and bilateral reduction mammoplasty using inverted-T incisions. The implant was confirmed as a smooth, silicone gel–filled mammary implant of 125 cm3 by a Japanese manufacturer, Koken. During her regular follow-up outpatient visits, physical examination revealed 2.5- × 1.5-cm ill-defined, tender, subcutaneous nodules on both knees and 8.5- × 3.0-cm inflammatory changes in the inguinal area with persistent pain. Computed tomography showed no definite mass, but rather infiltrative, nonenhancing soft-tissue densities in the subcutaneous layers of the bilateral inguinal and knee areas. Surgical excision was performed, and pathologic findings confirmed variable vacuoles with foreign body reaction and fibrosis, consistent with siliconoma. It is important to acknowledge that siliconomas can be encountered in patients with ruptured breast implants, especially those manufactured decades ago. Our patient with masses as remote as the inguinal and knee areas is a prime example of how far siliconomas can migrate. PMID:27826457

Microfabrication and characterization of an array of dielectric elastomer actuators generating uniaxial strain to stretch individual cells

NASA Astrophysics Data System (ADS)

Akbari, S.; Shea, H. R.

2012-04-01

Cells regulate their behavior in response to mechanical strains. Cell cultures to study mechanotransuction are typically cm2 in area, far too large to monitor single cell response. We have developed an array of dielectric elastomer microactuators as a tool to study mechanotransduction of individual cells. The array consists of 72 100 µm × 200 µm electroactive polymer actuators which expand uniaxially when a voltage is applied. Single cells will be attached on each actuator to study their response to periodic mechanical strains. The device is fabricated by patterning compliant microelectrodes on both sides of a 30 µm thick polydimethylsiloxane membrane, which is bonded to a Pyrex chip with 200 µm wide trenches. Low-energy metal ion implantation is used to make stretchable electrodes and we demonstrate here the successful miniaturization of such ion-implanted electrodes. The top electrode covers the full membrane area, while the bottom electrodes are 100 µm wide parallel lines, perpendicular to the trenches. Applying a voltage between the top and bottom electrodes leads to uniaxial expansion of the membrane at the intersection of the bottom electrodes and the trenches. To characterize the in-plane strain, an array of 4 µm diameter aluminum dots is deposited on each actuator. The position of each dot is tracked, allowing displacement and strain profiles to be measured as a function of voltage. The uniaxial strain reaches 4.7% at 2.9 kV with a 0.2 s response time, sufficient to stimulate most cells with relevant biological strains and frequencies.

A new type of recording chamber with an easy-to-exchange microdrive array for chronic recordings in macaque monkeys.

PubMed

Galashan, F Orlando; Rempel, Hanna C; Meyer, Anneke; Gruber-Dujardin, Eva; Kreiter, Andreas K; Wegener, Detlef

2011-06-01

In monkeys, long-term recordings with chronically implanted microelectrodes frequently suffer from a continuously decreasing probability to record single units or even small multiunit clusters. This problem is associated with two technical limitations of the available devices: first, restrictions for electrode movement, and second, absent possibility to exchange electrodes easily on a regular basis. Permitting to adjust the recording site and to use new recording tracks with proper electrodes may avoid these problems and make chronic more similar to acute recordings. Here, we describe a novel type of implant tackling this issue. It consists of a new type of recording chamber combined with an exchangeable multielectrode array that precisely fits into it. The multielectrode array is reversibly fixed to the chamber, and within a minute it can be exchanged against another array equipped with new electrodes at the awake animal. The array allows for bidirectional movement of six electrodes for a distance of up to 12 mm. The recording chamber enables hermetical isolation of the intracranial space, resulting in long-lasting aseptic conditions and reducing dural thickening to a minimum, as confirmed by microbiological and histopathological analysis. The device has a simple design and is both easy to produce and low in cost. Functionality has been tested in primary and secondary visual cortex of three macaque monkeys over a period of up to 15 mo. The results show that even after more than a year, single and multiunit responses can be obtained with high incidence.

Selective and graded recruitment of cat hamstring muscles with intrafascicular stimulation.

PubMed

Dowden, Brett R; Wilder, Andrew M; Hiatt, Scott D; Normann, Richard A; Brown, Nicholas A T; Clark, Gregory A

2009-12-01

The muscles of the hamstring group can produce different combinations of hip and knee torque. Thus, the ability to activate the different hamstring muscles selectively is of particular importance in eliciting functional movements such as stance and gait in a person with spinal cord injury. We investigated the ability of intrafascicular stimulation of the muscular branch of the sciatic nerve to recruit the feline hamstring muscles in a selective and graded fashion. A Utah Slanted Electrode Array, consisting of 100 penetrating microelectrodes, was implanted into the muscular branch of the sciatic nerve in six cats. Muscle twitches were evoked in the three compartments of biceps femoris (anterior, middle, and posterior), as well as semitendinosus and semimembranosus, using pulse-width modulated constant-voltage pulses. The resultant compound muscle action potentials were recorded using intramuscular fine-wire electrodes. 74% of the electrodes per implant were able to evoke a threshold response in these muscles, and these electrodes were evenly distributed among the instrumented muscles. Of the five muscles instrumented, on average 2.5 could be selectively activated to 90% of maximum EMG, and 3.5 could be selectively activated to 50% of maximum EMG. The muscles were recruited selectively with a mean stimulus dynamic range of 4.14 +/- 5.05 dB between threshold and either spillover to another muscle or a plateau in the response. This selective and graded activation afforded by intrafascicular stimulation of the muscular branch of the sciatic nerve suggests that it is a potentially useful stimulation paradigm for eliciting distinct forces in the hamstring muscle group in motor neuroprosthetic applications.

CranialVault and its CRAVE tools: a clinical computer assistance system for Deep Brain Stimulation (DBS) therapy

PubMed Central

D’Haese, Pierre-François; Pallavaram, Srivatsan; Li, Rui; Remple, Michael S.; Kao, Chris; Neimat, Joseph S.; Konrad, Peter E.; Dawant, Benoit M.

2010-01-01

A number of methods have been developed to assist surgeons at various stages of deep brain stimulation (DBS) therapy. These include construction of anatomical atlases, functional databases, and electrophysiological atlases and maps. But, a complete system that can be integrated into the clinical workflow has not been developed. In this paper we present a system designed to assist physicians in pre-operative target planning, intra-operative target refinement and implantation, and post-operative DBS lead programming. The purpose of this system is to centralize the data acquired a the various stages of the procedure, reduce the amount of time needed at each stage of the therapy, and maximize the efficiency of the entire process. The system consists of a central repository (CranialVault), of a suite of software modules called CRAVE (CRAnialVault Explorer) that permit data entry and data visualization at each stage of the therapy, and of a series of algorithms that permit the automatic processing of the data. The central repository contains image data for more than 400 patients with the related pre-operative plans and position of the final implants and about 10,550 electrophysiological data points (micro-electrode recordings or responses to stimulations) recorded from 222 of these patients. The system has reached the stage of a clinical prototype that is being evaluated clinically at our institution. A preliminary quantitative validation of the planning component of the system performed on 80 patients who underwent the procedure between January 2009 and December 2009 shows that the system provides both timely and valuable information. PMID:20732828

Intraoperative 3D Navigation for Single or Multiple 125I-Seed Localization in Breast-Preserving Cancer Surgery.

PubMed

Pouw, Bas; de Wit-van der Veen, Linda J; van Duijnhoven, Frederieke; Rutgers, Emiel J Th; Stokkel, Marcel P M; Valdés Olmos, Renato A; Vrancken Peeters, Marie-Jeanne T F D

2016-05-01

Mammographic screening has led to the identification of more women with nonpalpable breast cancer, many of them to be treated with breast-preserving surgery. To accomplish radical tumor excision, adequate localization techniques such as radioactive seed localization (RSL) are required. For RSL, a radioactive I-seed is implanted central in the tumor to enable intraoperative localization using a γ-probe. In case of extensive tumor or multifocal carcinoma, multiple I-seeds can be used to delineate the involved area. Preoperative imaging is performed different from surgical positioning; therefore, exact I-seed depth remains unknown during surgery. Twenty patients (mean age, 56.8 years) with 25 implanted I-seeds scheduled for RSL were included. Sixteen patients had 1 I-seed implanted in the primary lesion, 3 patients had 2 I-seeds, and 1 patient had 3 I-seeds. Freehand SPECT localized I-seeds by measuring γ-counts from different directions, all registered by an optical tracking system. A reconstruction and visualization algorithm enabled 3-dimensional (3D) navigation toward the I-seeds. Freehand SPECT visualized all I-seeds in primary tumors and provided preincision depth information. The deviation, mean (SD), between the freehand SPECT depth and the surgical depth estimation was 1.9 (2.1) mm (range, 0-7 mm). Three-dimensional freehand SPECT was especially useful identifying multiple implanted I-seeds because the conventional γ-probe has more difficulty discriminating I-seeds transcutaneous. Freehand SPECT with 3D navigation is a valuable tool in RSL for both single and multiple implanted I-seeds in breast-preserving cancer surgery. Freehand SPECT provides continuous updating 3D imaging with information about depth and location of the I-seeds contributing to adequate excision of nonpalpable breast cancer.

Evaluation of the Etiologies of Implant Fracture in Patients With Fractures of the Implants of Lower Limbs’ Long Bones

PubMed Central

Yeganeh, Ali; Otoukesh, Babak; Kaghazian, Peyman; Yeganeh, Nima; Boddohi, Bahram; Moghtadaei, Mehdi

2015-01-01

Background: Orthopedics implants are important tools for treatment of bone fractures. Despite available recommendations for designing and making the implants, there are multiple cases of fracture of these implants in the body. Hence, in this study the frequency of failure of implants in long bones of lower extremities was evaluated. Methods and Materials: In this cross-sectional study, two types of fractured implants in the body were analyzed and underwent metalogical, mechanical, and modeling and stress-bending analysis. Results: The results revealed that the main cause of fractures was decreased mechanical resistance due to inappropriate chemical composition (especially decreased percentages of Nickel and Molybdenum). Conclusions: It may be concluded that following the standard chemical composition and use of optimal making method are the most important works for prevention of failure of implants. PMID:26843735

Evaluation of high-density, multi-contact nerve cuffs for activation of grasp muscles in monkeys

NASA Astrophysics Data System (ADS)

Brill, N. A.; Naufel, S. N.; Polasek, K.; Ethier, C.; Cheesborough, J.; Agnew, S.; Miller, L. E.; Tyler, D. J.

2018-06-01

Objective. The objective of this work was to evaluate whether nerve cuffs can selectively activate hand muscles for functional electrical stimulation (FES). FES typically involves identifying and implanting electrodes in many individual muscles, but nerve cuffs only require implantation at a single site around the nerve. This method is surgically more attractive. Nerve cuffs may also more effectively stimulate intrinsic hand muscles, which are difficult to implant and stimulate without spillover to adjacent muscles. Approach. To evaluate its ability to selectively activate muscles, we implanted and tested the flat interface nerve electrode (FINE), which is designed to selectively stimulate peripheral nerves that innervate multiple muscles (Tyler and Durand 2002 IEEE Trans. Neural Syst. Rehabil. Eng. 10 294-303). We implanted FINEs on the nerves and bipolar intramuscular wires for recording compound muscle action potentials (CMAPs) from up to 20 muscles in each arm of six monkeys. We then collected recruitment curves while the animals were anesthetized. Main result. A single FINE implanted on an upper extremity nerve in the monkey can selectively activate muscles or small groups of muscles to produce multiple, independent hand functions. Significance. FINE cuffs can serve as a viable supplement to intramuscular electrodes in FES systems, where they can better activate intrinsic and extrinsic muscles with lower currents and less extensive surgery.

Microelectrode voltammetry of multi-electron transfers complicated by coupled chemical equilibria: a general theory for the extended square scheme.

PubMed

Laborda, Eduardo; Gómez-Gil, José María; Molina, Angela

2017-06-28

A very general and simple theoretical solution is presented for the current-potential-time response of reversible multi-electron transfer processes complicated by homogeneous chemical equilibria (the so-called extended square scheme). The expressions presented here are applicable regardless of the number of electrons transferred and coupled chemical processes, and they are particularized for a wide variety of microelectrode geometries. The voltammetric response of very different systems presenting multi-electron transfers is considered for the most widely-used techniques (namely, cyclic voltammetry, square wave voltammetry, differential pulse voltammetry and steady state voltammetry), studying the influence of the microelectrode geometry and the number and thermodynamics of the (electro)chemical steps. Most appropriate techniques and procedures for the determination of the 'interaction' between successive transfers are discussed. Special attention is paid to those situations where homogeneous chemical processes, such as protonation, complexation or ion association, affect the electrochemical behaviour of the system by different stabilization of the oxidation states.

SU-8 microprobe with microelectrodes for monitoring electrical impedance in living tissues.

PubMed

Tijero, M; Gabriel, G; Caro, J; Altuna, A; Hernández, R; Villa, R; Berganzo, J; Blanco, F J; Salido, R; Fernández, L J

2009-04-15

This paper presents a minimally invasive needle-shaped probe capable of monitoring the electrical impedance of living tissues. This microprobe consists of a 160 microm thick SU-8 substrate containing four planar platinum (Pt) microelectrodes. We design the probe to minimize damage to the surrounding tissue and to be stiff enough to be inserted in living tissues. The proposed batch fabrication process is low cost and low time consuming. The microelectrodes obtained with this process are strongly adhered to the SU-8 substrate and their impedance does not depend on frequency variation. In vitro experiments are compared with previously developed Si and SiC based microprobes and results suggest that it is preferable to use the SU-8 based microprobes due to their flexibility and low cost. The microprobe is assembled on a flexible printed circuit FPC with a conductive glue, packaged with epoxy and wired to the external instrumentation. This flexible probe is inserted into a rat kidney without fracturing and succeeds in demonstrating the ischemia monitoring.

Fabrication of oxocuprate superconductor microelectrodes for sub-{Tc} use

DOE Office of Scientific and Technical Information (OSTI.GOV)

Green, S.J.; Rosseinsky, D.R.; Toohey, M.J.

1995-07-01

The technique of partial resin encapsulation is described for the direct fabrication of cryorobust oxocuprate microelectrodes from bulk ceramic samples, here Bi{sub 2}Sr{sub 2}CaCu{sub 2}O{sub 8{minus}{delta}}, Bi{sub 2}Sr{sub 2}Ca{sub 2}Cu{sub 3}O{sub 10{minus}{delta}}. Cyclic voltammetry is used in tests of the electrochemical response at 295 K (ferrocene in acetonitrile/NBu{sub 4}BF{sub 4}), affording approximated disk radii 2.9, 37.0, and 32.5 {micro}m, and at 123 and at 103 K (ferrocene in chloroethane/tetrahydrofuran/LiBF{sub 4}). Some nonideality in the 295 K responses results from electrode porosity and, at the smallest electrodes, defects in the HTSC/resin seal. Acceptable sub-T{sub c} responses show these problems to bemore » irrelevant in the high viscosity of the electrolytes at low temperature. These microelectrodes usefully advance the emerging study of electrochemistry on superconducting electrodes by responding to free-solute electroactives at <{Tc}.« less

Fabrication of gas sensor based on field ionization from SWCNTs with tripolar microelectrode

NASA Astrophysics Data System (ADS)

Cai, Shengbing; Zhang, Yong; Duan, Zhemin

2012-12-01

We report the nanofabrication of a sulfur dioxide (SO2) sensor with a tripolar on-chip microelectrode utilizing a film of single-walled carbon nanotubes (SWCNTs) as the field ionization cathode, where the ion flow current and the partial discharge current generated by the field ionization process of gaseous molecules can be gauged to gas species and concentration. The variation of the sensitivity is less than 4% for all of the tested devices, and the sensor has selectivity against gases such as He, NO2, CO, H2, SO2 and O2. Further, the sensor response presents well-defined and reproducible linear behavior with regard to concentration in the range investigated and a detection limitation of <˜0.5 ppm for SO2. More importantly, a tripolar on-chip microelectrode with SWCNTs as a cathode exhibits an impressive performance with respect to stability and anti-oxidation behavior, which are significantly better than had been possible before in the traditional bipolar sensor under explicit circumstances at room temperature.

Development and characterization of a voltammetric carbon-fiber microelectrode pH sensor.

PubMed

Makos, Monique A; Omiatek, Donna M; Ewing, Andrew G; Heien, Michael L

2010-06-15

This work describes the development and characterization of a modified carbon-fiber microelectrode sensor capable of measuring real-time physiological pH changes in biological microenvironments. The reagentless sensor was fabricated under ambient conditions from voltammetric reduction of the diazonium salt Fast Blue RR onto a carbon-fiber surface in aprotic media. Fast-scan cyclic voltammetry was used to probe redox activity of the p-quinone moiety of the surface-bound molecule as a function of pH. In vitro calibration of the sensor in solutions ranging from pH 6.5 to 8.0 resulted in a pH-dependent anodic peak potential response. Flow-injection analysis was used to characterize the modified microelectrode, revealing sensitivity to acidic and basic changes discernible to 0.005 pH units. Furthermore, the modified electrode was used to measure dynamic in vivo pH changes evoked during neurotransmitter release in the central nervous system of the microanalytical model organism Drosophila melanogaster.

Highly sensitive detection of quantal dopamine secretion from pheochromocytoma cells using neural microelectrode array electrodeposited with polypyrrole graphene.

PubMed

Wang, Li; Xu, Huiren; Song, Yilin; Luo, Jinping; Wei, Wenjing; Xu, Shengwei; Cai, Xinxia

2015-04-15

For the measurement of events of dopamine (DA) release as well as the coordinating neurotransmission in the nerve system, a neural microelectrode array (nMEA) electrodeposited directionally with polypyrrole graphene (PG) nanocomposites was fabricated. The deposited graphene significantly increased the surface area of working electrode, which led to the nMEA (with diameter of 20 μm) with excellent selectivity and sensitivity to DA. Furthermore, PG film modification exhibited low detection limit (4 nM, S/N = 3.21), high sensitivity, and good linearity in the presence of ascorbic acid (e.g., 13933.12 μA mM(-1) cm(-2) in the range of 0.8-10 μM). In particular, the nMEA combined with the patch-clamp system was used to detect quantized DA release from pheochromocytoma cells under 100 mM K(+) stimulation. The nMEA that integrates 60 microelectrodes is novel for detecting a large number of samples simultaneously, which has potential for neural communication research.

Measurement of Net Fluxes of Ammonium and Nitrate at the Surface of Barley Roots Using Ion-Selective Microelectrodes 1

PubMed Central

Henriksen, Gordon H.; Raman, D. Raj; Walker, Larry P.; Spanswick, Roger M.

1992-01-01

Net fluxes of NH4+ and NO3− into roots of 7-day-old barley (Hordeum vulgare L. cv Prato) seedlings varied both with position along the root axis and with time. These variations were not consistent between replicate plants; different roots showed unique temporal and spatial patterns of uptake. Axial scans of NH4+ and NO3− net fluxes were conducted along the apical 7 centimeters of seminal roots of intact barley seedlings in solution culture using ion-selective microelectrodes in the unstirred layer immediately external to the root surface. Theoretically derived relationships between uptake and concentration gradients, combined with experimental observations of the conditions existing in our experimental system, permitted evaluation of the contribution of bulk water flow to ion movement in the unstirred layer, as well as a measure of the spatial resolution of the microelectrode flux estimation technique. Finally, a method was adopted to assess the accuracy of this technique. PMID:16668947

Development and Characterization of a Voltammetric Carbon-fiber Microelectrode pH Sensor

PubMed Central

Makos, Monique A.; Omiatek, Donna M.; Ewing, Andrew G.; Heien, Michael L.

2010-01-01

This work describes the development and characterization of a modified carbon-fiber microelectrode sensor capable of measuring real-time physiological pH changes in biological microenvironments. The reagentless sensor was fabricated under ambient conditions from voltammetric reduction of the diazonium salt Fast Blue RR onto a carbon-fiber surface in aprotic media. Fast-scan cyclic voltammetry was used to probe redox activity of the p-quinone moiety of the surface-bound molecule as a function of pH. In vitro calibration of the sensor in solutions ranging from pH 6.5 to 8.0 resulted in a pH-dependent anodic peak potential response. Flow-injection analysis was used to characterize the modified microelectrode, revealing sensitivity to acidic and basic changes discernable to 0.005 pH units. Furthermore, the modified electrode was used to measure dynamic in vivo pH changes evoked during neurotransmitter release in the central nervous system of the microanalytical model organism Drosophila melanogaster. PMID:20380393

3D plasmonic nanoantennas integrated with MEA biosensors

NASA Astrophysics Data System (ADS)

Dipalo, Michele; Messina, Gabriele C.; Amin, Hayder; La Rocca, Rosanna; Shalabaeva, Victoria; Simi, Alessandro; Maccione, Alessandro; Zilio, Pierfrancesco; Berdondini, Luca; de Angelis, Francesco

2015-02-01

Neuronal signaling in brain circuits occurs at multiple scales ranging from molecules and cells to large neuronal assemblies. However, current sensing neurotechnologies are not designed for parallel access of signals at multiple scales. With the aim of combining nanoscale molecular sensing with electrical neural activity recordings within large neuronal assemblies, in this work three-dimensional (3D) plasmonic nanoantennas are integrated with multielectrode arrays (MEA). Nanoantennas are fabricated by fast ion beam milling on optical resist; gold is deposited on the nanoantennas in order to connect them electrically to the MEA microelectrodes and to obtain plasmonic behavior. The optical properties of these 3D nanostructures are studied through finite elements method (FEM) simulations that show a high electromagnetic field enhancement. This plasmonic enhancement is confirmed by surface enhancement Raman spectroscopy of a dye performed in liquid, which presents an enhancement of almost 100 times the incident field amplitude at resonant excitation. Finally, the reported MEA devices are tested on cultured rat hippocampal neurons. Neurons develop by extending branches on the nanostructured electrodes and extracellular action potentials are recorded over multiple days in vitro. Raman spectra of living neurons cultured on the nanoantennas are also acquired. These results highlight that these nanostructures could be potential candidates for combining electrophysiological measures of large networks with simultaneous spectroscopic investigations at the molecular level.Neuronal signaling in brain circuits occurs at multiple scales ranging from molecules and cells to large neuronal assemblies. However, current sensing neurotechnologies are not designed for parallel access of signals at multiple scales. With the aim of combining nanoscale molecular sensing with electrical neural activity recordings within large neuronal assemblies, in this work three-dimensional (3D) plasmonic nanoantennas are integrated with multielectrode arrays (MEA). Nanoantennas are fabricated by fast ion beam milling on optical resist; gold is deposited on the nanoantennas in order to connect them electrically to the MEA microelectrodes and to obtain plasmonic behavior. The optical properties of these 3D nanostructures are studied through finite elements method (FEM) simulations that show a high electromagnetic field enhancement. This plasmonic enhancement is confirmed by surface enhancement Raman spectroscopy of a dye performed in liquid, which presents an enhancement of almost 100 times the incident field amplitude at resonant excitation. Finally, the reported MEA devices are tested on cultured rat hippocampal neurons. Neurons develop by extending branches on the nanostructured electrodes and extracellular action potentials are recorded over multiple days in vitro. Raman spectra of living neurons cultured on the nanoantennas are also acquired. These results highlight that these nanostructures could be potential candidates for combining electrophysiological measures of large networks with simultaneous spectroscopic investigations at the molecular level. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05578k

Methods for automatic detection of artifacts in microelectrode recordings.

PubMed

Bakštein, Eduard; Sieger, Tomáš; Wild, Jiří; Novák, Daniel; Schneider, Jakub; Vostatek, Pavel; Urgošík, Dušan; Jech, Robert

2017-10-01

Extracellular microelectrode recording (MER) is a prominent technique for studies of extracellular single-unit neuronal activity. In order to achieve robust results in more complex analysis pipelines, it is necessary to have high quality input data with a low amount of artifacts. We show that noise (mainly electromagnetic interference and motion artifacts) may affect more than 25% of the recording length in a clinical MER database. We present several methods for automatic detection of noise in MER signals, based on (i) unsupervised detection of stationary segments, (ii) large peaks in the power spectral density, and (iii) a classifier based on multiple time- and frequency-domain features. We evaluate the proposed methods on a manually annotated database of 5735 ten-second MER signals from 58 Parkinson's disease patients. The existing methods for artifact detection in single-channel MER that have been rigorously tested, are based on unsupervised change-point detection. We show on an extensive real MER database that the presented techniques are better suited for the task of artifact identification and achieve much better results. The best-performing classifiers (bagging and decision tree) achieved artifact classification accuracy of up to 89% on an unseen test set and outperformed the unsupervised techniques by 5-10%. This was close to the level of agreement among raters using manual annotation (93.5%). We conclude that the proposed methods are suitable for automatic MER denoising and may help in the efficient elimination of undesirable signal artifacts. Copyright © 2017 Elsevier B.V. All rights reserved.

Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials.

PubMed

Riisager, Anders; Duehmke, Rudy; Nielsen, Ole Bækgaard; Huang, Christopher L; Pedersen, Thomas Holm

2014-10-15

Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (Gm) that reflect regulation of ClC-1 Cl(-) and KATP K(+) ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (Rin) in between action potential trains. Since the fibre length constant (λ) could not be determined, however, the calculation of Gm relied on the assumptions that the specific cytosolic resistivity (Ri) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three-microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including Rin and λ as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and Ri. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in Gm that were eventually followed by a ∼3-fold, fully reversible increase in Gm after the firing of 1450-1800 action potentials. Using this three-electrode method we further show that the latter rise in Gm was closely associated with excitation failures and loss of action potential signal above -20 mV. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

High-throughput cardiac safety evaluation and multi-parameter arrhythmia profiling of cardiomyocytes using microelectrode arrays.

PubMed

Gilchrist, Kristin H; Lewis, Gregory F; Gay, Elaine A; Sellgren, Katelyn L; Grego, Sonia

2015-10-15

Microelectrode arrays (MEAs) recording extracellular field potentials of human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) provide a rich data set for functional assessment of drug response. The aim of this work is the development of a method for a systematic analysis of arrhythmia using MEAs, with emphasis on the development of six parameters accounting for different types of cardiomyocyte signal irregularities. We describe a software approach to carry out such analysis automatically including generation of a heat map that enables quick visualization of arrhythmic liability of compounds. We also implemented signal processing techniques for reliable extraction of the repolarization peak for field potential duration (FPD) measurement even from recordings with low signal to noise ratios. We measured hiPS-CM's on a 48 well MEA system with 5minute recordings at multiple time points (0.5, 1, 2 and 4h) after drug exposure. We evaluated concentration responses for seven compounds with a combination of hERG, QT and clinical proarrhythmia properties: Verapamil, Ranolazine, Flecainide, Amiodarone, Ouabain, Cisapride, and Terfenadine. The predictive utility of MEA parameters as surrogates of these clinical effects were examined. The beat rate and FPD results exhibited good correlations with previous MEA studies in stem cell derived cardiomyocytes and clinical data. The six-parameter arrhythmia assessment exhibited excellent predictive agreement with the known arrhythmogenic potential of the tested compounds, and holds promise as a new method to predict arrhythmic liability. Copyright © 2015 Elsevier Inc. All rights reserved.

Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials

PubMed Central

Riisager, Anders; Duehmke, Rudy; Nielsen, Ole Bækgaard; Huang, Christopher L; Pedersen, Thomas Holm

2014-01-01

Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (Gm) that reflect regulation of ClC-1 Cl− and KATP K+ ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (Rin) in between action potential trains. Since the fibre length constant (λ) could not be determined, however, the calculation of Gm relied on the assumptions that the specific cytosolic resistivity (Ri) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three-microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including Rin and λ as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and Ri. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in Gm that were eventually followed by a ∼3-fold, fully reversible increase in Gm after the firing of 1450–1800 action potentials. Using this three-electrode method we further show that the latter rise in Gm was closely associated with excitation failures and loss of action potential signal above −20 mV. PMID:25128573

Time-dependent Increase in the Network Response to the Stimulation of Neuronal Cell Cultures on Micro-electrode Arrays.

PubMed

Gertz, Monica L; Baker, Zachary; Jose, Sharon; Peixoto, Nathalia

2017-05-29

Micro-electrode arrays (MEAs) can be used to investigate drug toxicity, design paradigms for next-generation personalized medicine, and study network dynamics in neuronal cultures. In contrast with more traditional methods, such as patch-clamping, which can only record activity from a single cell, MEAs can record simultaneously from multiple sites in a network, without requiring the arduous task of placing each electrode individually. Moreover, numerous control and stimulation configurations can be easily applied within the same experimental setup, allowing for a broad range of dynamics to be explored. One of the key dynamics of interest in these in vitro studies has been the extent to which cultured networks display properties indicative of learning. Mouse neuronal cells cultured on MEAs display an increase in response following training induced by electrical stimulation. This protocol demonstrates how to culture neuronal cells on MEAs; successfully record from over 95% of the plated dishes; establish a protocol to train the networks to respond to patterns of stimulation; and sort, plot, and interpret the results from such experiments. The use of a proprietary system for stimulating and recording neuronal cultures is demonstrated. Software packages are also used to sort neuronal units. A custom-designed graphical user interface is used to visualize post-stimulus time histograms, inter-burst intervals, and burst duration, as well as to compare the cellular response to stimulation before and after a training protocol. Finally, representative results and future directions of this research effort are discussed.

Basolateral K channels in an insect epithelium. Channel density, conductance, and block by barium

PubMed Central

Hanrahan, JW; Wills, NK; Phillips, JE; Lewis, SA

1986-01-01

K channels in the basolateral membrane of insect hindgut were studied using current fluctuation analysis and microelectrodes. Locust recta were mounted in Ussing-type chambers containing Cl-free saline and cyclic AMP (cAMP). A transepithelial K current was induced by raising serosal [K] under short-circuit conditions. Adding Ba to the mucosal (luminal) side under these conditions had no effect; however, serosal Ba reversibly inhibited the short-circuit current (Isc), increased transepithelial resistance (Rt), and added a Lorentzian component to power density spectra of the Isc. A nonlinear relationship between corner frequency and serosal [Ba] was observed, which suggests that the rate constant for Ba association with basolateral channels increased as [Ba] was elevated. Microelectrode experiments revealed that the basolateral membrane hyperpolarized when Ba was added: this change in membrane potential could explain the nonlinearity of the 2 pi fc vs. [Ba] relationship if external Ba sensed about three-quarters of the basolateral membrane field. Conventional microelectrodes were used to determine the correspondence between transepithelially measured current noise and basolateral membrane conductance fluctuations, and ion-sensitive microelectrodes were used to measure intracellular K activity (acK). From the relationship between the net electrochemical potential for K across the basolateral membrane and the single channel current calculated from noise analysis, we estimate that the conductance of basolateral K channels is approximately 60 pS, and that there are approximately 180 million channels per square centimeter of tissue area. PMID:2420918

Infection after pacemaker implantation: infection rates and risk factors associated with infection in a population-based cohort study of 46299 consecutive patients

PubMed Central

Johansen, Jens Brock; Jørgensen, Ole Dan; Møller, Mogens; Arnsbo, Per; Mortensen, Peter Thomas; Nielsen, Jens Cosedis

2011-01-01

Aims Infection is a serious complication of pacemaker (PM) systems. Although the rate of infection has been debated, the figures are largely unknown. We therefore studied the incidence of PM infection and its associated risk factors in the Danish population. Methods and results Since 1982, all PM implantation and removal procedures performed in Denmark have been prospectively recorded in the Danish Pacemaker Register. All patients (n = 46299) who underwent implantation between 1982 and 2007 were included. The total length of surveillance was 236 888 PM-years. The incidence of infection was calculated according to the total number of PM-years. The incidence of surgical site infection (≤365 days after PM implantation) was compared with later infection in first implant and replacement procedures. Multiple-record and multiple-event-per-subject proportional hazards analyses were used to identify the independent risk factors of PM infection. Surgical site infection occurred in 192 cases after first implantation (incidence rate 4.82/1000 PM-years), and in 133 cases after replacement (12.12/1000 PM-years). Infections occurring more than 365 days after the first implantation occurred in 153 cases (1.02/1000 PM-years), and in 118 cases after replacement (3.26/1000 PM-years). Independent factors associated with an increased risk of PM infection were a greater number of PM operations (including replacements), male sex, younger age, implantation during the earliest part of the study period, and absence of antibiotics (P< 0.001). Conclusion The overall risk of infection after PM implantation was low. A greater number of operations augmented the risk of infection. This should be taken into account when considering revisions of PM systems. PMID:21252172

Evaluation of fracture torque resistance of orthodontic mini-implants.

PubMed

Dalla Rosa, Fernando; Burmann, Paola Fp; Ruschel, Henrique C; Vargas, Ivana A; Kramer, Paulo F

2016-12-01

This study sought to assess the fracture torque resistance of mini-implants used for orthodontic anchorage. Five commercially available brands of mini-implants were used (SIN®, CONEXÃO®, NEODENT®, MORELLI®, andFORESTADENT®). Ten mini-implants of each diameter of each brand were tested, for a total 100 specimens. The mini-implants were subject to a static torsion test as described in ASTMstandard F543. Analysis of variance (ANOVA) with the Tukey multiple comparisons procedure was used to assess results. Overall, mean fracture strength ranged from 15.7 to 70.4 N·cm. Mini-implants with larger diameter exhibited higher peak torque values at fracture and higher yield strength, regardless of brand. In addition, significant differences across brands were observed when implants were stratified by diameter. In conclusion, larger mini-implant diameter is associated with increased fracture torque resistance. Additional information on peak torque values at fracture of different commercial brands of mini-implants may increase the success rate of this orthodontic anchorage modality. Sociedad Argentina de Investigación Odontológica.

The upregulation of specific interleukin (IL) receptor antagonists and paradoxical enhancement of neuronal apoptosis due to electrode induced strain and brain micromotion.

PubMed

Karumbaiah, Lohitash; Norman, Sharon E; Rajan, Nithish B; Anand, Sanjay; Saxena, Tarun; Betancur, Martha; Patkar, Radhika; Bellamkonda, Ravi V

2012-09-01

The high mechanical mismatch between stiffness of silicon and metal microelectrodes and soft cortical tissue, induces strain at the neural interface which likely contributes to failure of the neural interface. However, little is known about the molecular outcomes of electrode induced low-magnitude strain (1-5%) on primary astrocytes, microglia and neurons. In this study we simulated brain micromotion at the electrode-brain interface by subjecting astrocytes, microglia and primary cortical neurons to low-magnitude cyclical strain using a biaxial stretch device, and investigated the molecular outcomes of induced strain in vitro. In addition, we explored the functional consequence of astrocytic and microglial strain on neural health, when they are themselves subjected to strain. Quantitative real-time PCR array (qRT-PCR Array) analysis of stretched astrocytes and microglia showed strain specific upregulation of an Interleukin receptor antagonist - IL-36Ra (previously IL-1F5), to ≈ 1018 and ≈ 236 fold respectively. Further, IL-36Ra gene expression remained unchanged in astrocytes and microglia treated with bacterial lipopolysaccharide (LPS) indicating that the observed upregulation in stretched astrocytes and microglia is potentially strain specific. Zymogram and western blot analysis revealed that mechanically strained astrocytes and microglia upregulated matrix metalloproteinases (MMPs) 2 and 9, and other markers of reactive gliosis such as glial fibrillary acidic protein (GFAP) and neurocan when compared to controls. Primary cortical neurons when stretched with and without IL-36Ra, showed a ≈ 400 fold downregulation of tumor necrosis factor receptor superfamily, member 11b (TNFRSF11b). Significant upregulation of members of the caspase cysteine proteinase family and other pro-apoptotic genes was also observed in the presence of IL-36Ra than in the absence of IL-36Ra. Adult rats when implanted with microwire electrodes showed upregulation of IL-36Ra (≈ 20 fold) and IL-1Ra (≈ 1500 fold) 3 days post-implantation (3 DPI), corroborating in vitro results, although these transcripts were drastically down regulated by ≈ 20 fold and ≈ 1488 fold relative to expression levels 3 DPI, at the end of 12 weeks post-implantation (12 WPI). These results demonstrate that IL receptor antagonists may be negatively contributing to neuronal health at acute time-points post-electrode implantation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ahmed glaucoma valve implant: surgical technique and complications.

PubMed

Riva, Ivano; Roberti, Gloria; Oddone, Francesco; Konstas, Anastasios Gp; Quaranta, Luciano

2017-01-01

Implantation of Ahmed glaucoma valve is an effective surgical technique to reduce intraocular pressure in patients affected with glaucoma. While in the past, the use of this device was reserved to glaucoma refractory to multiple filtration surgical procedures, up-to-date mounting experience has encouraged its use also as a primary surgery for selected cases. Implantation of Ahmed glaucoma valve can be challenging for the surgeon, especially in patients who already underwent previous multiple surgeries. Several tips have to be acquired by the surgeon, and a long learning curve is always needed. Although the valve mechanism embedded in the Ahmed glaucoma valve decreases the risk of postoperative hypotony-related complications, it does not avoid the need of a careful follow-up. Complications related to this type of surgery include early and late postoperative hypotony, excessive capsule fibrosis around the plate, erosion of the tube or plate edge, and very rarely infection. The aim of this review is to describe surgical technique for Ahmed glaucoma valve implantation and to report related complications.

Ahmed glaucoma valve implant: surgical technique and complications

PubMed Central

Riva, Ivano; Roberti, Gloria; Oddone, Francesco; Konstas, Anastasios GP; Quaranta, Luciano

2017-01-01

Implantation of Ahmed glaucoma valve is an effective surgical technique to reduce intraocular pressure in patients affected with glaucoma. While in the past, the use of this device was reserved to glaucoma refractory to multiple filtration surgical procedures, up-to-date mounting experience has encouraged its use also as a primary surgery for selected cases. Implantation of Ahmed glaucoma valve can be challenging for the surgeon, especially in patients who already underwent previous multiple surgeries. Several tips have to be acquired by the surgeon, and a long learning curve is always needed. Although the valve mechanism embedded in the Ahmed glaucoma valve decreases the risk of postoperative hypotony-related complications, it does not avoid the need of a careful follow-up. Complications related to this type of surgery include early and late postoperative hypotony, excessive capsule fibrosis around the plate, erosion of the tube or plate edge, and very rarely infection. The aim of this review is to describe surgical technique for Ahmed glaucoma valve implantation and to report related complications. PMID:28255226

Scanning electron microscopy fractography analysis of fractured hollow implants.

PubMed

Sbordone, Ludovico; Traini, Tonino; Caputi, Sergio; Scarano, Antonio; Bortolaia, Claudia; Piattelli, Adriano

2010-01-01

Fracture of the implant is one of the possible complications affecting dental implants; it is a rare event but of great clinical relevance. The aim of the present study was to perform a scanning electron microscopy (SEM) fractography evaluation of 7 International Team for oral Implantology (ITI) hollow implants removed because of fracture. The most common clinical risk factors, such as malocclusion, bruxism, and cantilevers on the prosthesis, were absent. Seven fractured ITI hollow implants were retrieved from 5 patients and were analyzed with the use of SEM. SEM analysis showed typical signs of a cleavage-type fracture. Fractures could be due to an association of multiple factors such as fatigue, inner defects, material electrochemical problems, and tensocorrosion.

The NASA Smart Probe Project for real-time multiple microsensor tissue recognition

NASA Technical Reports Server (NTRS)

Andrews, Russell J.; Mah, Robert W.

2003-01-01

BACKGROUND: Remote surgery requires automated sensors, effectors and sensor-effector communication. The NASA Smart Probe Project has focused on the sensor aspect. METHODS: The NASA Smart Probe uses neural networks and data from multiple microsensors for a unique tissue signature in real time. Animal and human trials use several probe configurations: (1) 8-microsensor probe (2.5 mm in diameter) for rodent studies (normal and subcutaneous mammary tumor tissues), and (2) 21-gauge needle probe with 3 spectroscopic fibers and an impedance microelectrode for breast cancer diagnosis in humans. Multisensor data are collected in real time (update 100 times/s) using PCs. RESULTS: Human data (collected by NASA licensee BioLuminate) from 15 women undergoing breast biopsy distinguished normal tissue from both benign tumors and breast carcinoma. Tumor margins and necrosis are rapidly detected. CONCLUSION: Real-time tissue identification is achievable. Potential applications, including probes incorporating nanoelectrode arrays, are presented. Copyright 2003 S. Karger AG, Basel.

Quantitative weaknesses of the Marcus-Hush theory of electrode kinetics revealed by Reverse Scan Square Wave Voltammetry: The reduction of 2-methyl-2-nitropropane at mercury microelectrodes

NASA Astrophysics Data System (ADS)

Laborda, Eduardo; Wang, Yijun; Henstridge, Martin C.; Martínez-Ortiz, Francisco; Molina, Angela; Compton, Richard G.

2011-08-01

The Marcus-Hush and Butler-Volmer kinetic electrode models are compared experimentally by studying the reduction of 2-methyl-2-nitropropane in acetonitrile at mercury microelectrodes using Reverse Scan Square Wave Voltammetry. This technique is found to be very sensitive to the electrode kinetics and to permit critical comparison of the two models. The Butler-Volmer model satisfactorily fits the experimental data whereas Marcus-Hush does not quantitatively describe this redox system.

75 FR 69591 - Medicaid Program; Withdrawal of Determination of Average Manufacturer Price, Multiple Source Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-15

... issue a proposed regulation addressing the Affordable Care Act provisions. Inhalation, Infusion..., infusion, instilled, implanted and injectable drugs that are not generally dispensed through retail... publish a list of drugs that meet the statutory definition of inhalation, infusion, instilled, implanted...

Modified titanium implant as a gateway to the human body: the implant mediated drug delivery system.

PubMed

Park, Young-Seok; Cho, Joo-Youn; Lee, Shin-Jae; Hwang, Chee Il

2014-01-01

The aim of this study was to investigate the efficacy of a proposed new implant mediated drug delivery system (IMDDS) in rabbits. The drug delivery system is applied through a modified titanium implant that is configured to be implanted into bone. The implant is hollow and has multiple microholes that can continuously deliver therapeutic agents into the systematic body. To examine the efficacy and feasibility of the IMDDS, we investigated the pharmacokinetic behavior of dexamethasone in plasma after a single dose was delivered via the modified implant placed in the rabbit tibia. After measuring the plasma concentration, the areas under the curve showed that the IMDDS provided a sustained release for a relatively long period. The result suggests that the IMDDS can deliver a sustained release of certain drug components with a high bioavailability. Accordingly, the IMDDS may provide the basis for a novel approach to treating patients with chronic diseases.

Dual-modal photoacoustic and ultrasound imaging of dental implants

NASA Astrophysics Data System (ADS)

Lee, Donghyun; Park, Sungjo; Kim, Chulhong

2018-02-01

Dental implants are common method to replace decayed or broken tooth. As the implant treatment procedures varies according to the patients' jawbone, bone ridge, and sinus structure, appropriate examinations are necessary for successful treatment. Currently, radiographic examinations including periapical radiology, panoramic X-ray, and computed tomography are commonly used for diagnosing and monitoring. However, these radiographic examinations have limitations in that patients and operators are exposed to radioactivity and multiple examinations are performed during the treatment. In this study, we demonstrated photoacoustic (PA) and ultrasound (US) combined imaging of dental implant that can lower the total amount of absorbed radiation dose in dental implant treatment. An acoustic resolution PA macroscopy and a clinical PA/US system was used for dental implant imaging. The acquired dual modal PA/US imaging results support that the proposed photoacoustic imaging strategy can reduce the radiation dose rate during dental implant treatment.

Clinical Considerations of Adapted Drilling Protocol by Bone Quality Perception.

PubMed

Toia, Marco; Stocchero, Michele; Cecchinato, Francesca; Corrà, Enrico; Jimbo, Ryo; Cecchinato, Denis

To evaluate insertion torque value (ITV) and marginal bone loss (MBL) of an implant system after a clinically perceived bone quality-adapted drilling. This multicenter retrospective study included patients treated with implants, conventionally loaded, in completely healed sites. Operators customized the osteotomy preparation according to radiographic assessment and their perception of bone quality. Drilling sequence, bone quality, and ITV were recorded at the time of surgery. Radiographs were taken at the time of implant placement and permanent restoration. MBL between implant placement and permanent restoration was calculated. The implant was used as the statistical unit. Demographic and implant characteristics were shown by means of descriptive statistics. Outcome values were compared using analysis of variance (ANOVA) and Kruskal-Wallis tests. Multiple regression models were used to test the effect of independent variables on ITV and MBL. One hundred eighty-eight implants placed in 87 patients were included in the analysis. The mean observation period was 144 ± 59 days. The mean ITV was 30.8 ± 15.1 Ncm. ITV differed significantly based on arches (mandible/maxilla) (P = .001), bone quality (P < .001), implant diameter (P = .032), and drilling protocol (P = .019). Median MBL was 0.05 mm (0.00; 0.24). A significant difference was found between the mandible and maxilla (P = .008) and between drilling protocols (P = .011). In particular, significantly higher MBL was found in the undersized drilling protocol. Multiple regression analysis showed that ITV was influenced by bone quality and implant diameter. MBL was influenced by bone quality, implant diameter, ITV, and the interaction between bone quality and ITV. It was estimated that MBL was greater with increased bone density and ITV. Excessive ITV in dense bone can cause negative marginal bone responses. A presurgical radiographic assessment and the perception of bone quality are necessary to select an optimal drilling protocol and to minimize surgical trauma.

Multidisciplinary management including periodontics, orthodontics, implants, and prosthetics for an adult.

PubMed

Pinho, Teresa; Neves, Manuel; Alves, Célia

2012-08-01

This article describes the complex dental treatment of an adult patient with multiple missing teeth, mild chronic periodontitis, and a malocclusion with a cant of the occlusal plane. After periodontal treatment, titanium implants and a miniscrew were placed to correct the occlusal plane canting with orthodontic treatment. Prosthodontic treatment was completed by using osseointegrated implants to replace the missing teeth. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Influence of different materials and techniques to transfer molding in multiple implants.

PubMed

Faria, Júlio C B; Cruz, Fernando L G; Silva-Concílio, Laís R; Neves, Ana C C

2012-01-01

The aim of this study was to compare different materials and techniques used in transfer molding of multiple implants, by evaluating the space between implants and superstructure. Four external hexagon implants were fixed in a master template and the same on a superstructure. Transfer molding of implants were done using the direct and indirect techniques, with transfers united or not, using the union chemically activated acrylic resin (QA) and other groups polymerized acrylic resin (FT), and sectioned and not split. The casts were made with polyether and models divided into 8 groups (n = 5). The space between the superstructure and the master implants was measured with a microscope and the data was analyzed statistically by Student's t test (p < 0.05). For the material of union there was no significant difference, except when the groups were compared with the resin Duralay QA (G4) and the resin Duolay FT (G8) and groups using resins Duolay QA (G5) and Duolay FT (G7) for the union of the transfers. When comparing the groups who had the union between the transfers and sectioned again united with those in which the union was not severed there was no statistically significant difference. QA resin was superior to the FT with respect to the union of transfers. Techniques with united transfers or not were similar.

Identification and Multiplicity of Double Vowels in Cochlear Implant Users

ERIC Educational Resources Information Center

Kwon, Bomjun J.; Perry, Trevor T.

2014-01-01

Purpose: The present study examined cochlear implant (CI) users' perception of vowels presented concurrently (i.e., "double vowels") to further our understanding of auditory grouping in electric hearing. Method: Identification of double vowels and single vowels was measured with 10 CI subjects. Fundamental frequencies (F0s) of…

Estimation of the membrane potential of cultured macrophages from the fast potential transient upon microelectrode entry

PubMed Central

Ince, C; Ypey, DL; Van Furth, R; Verveen, AA

1983-01-01

Analysis of membrane potential recordings upon microelectrode impalement of four types of macrophages (cell lines P388D1 and PU5-1.8, cultured mouse peritoneal macrophages, and cultured human monocytes) reveals that these cells have membrane potentials at least two times more negative than sustained potential values (E(s)) frequently reported. Upon microelectrode entry into the cell (P388D1), the recorded potential drops to a peak value (E(p)) (mean -37 mV for 50 cells, range -15 to -70 mV) within 2 ms, after which it decays to a depolarized potential (E(n)) (mean -12 mV) in about 20 ms. Thereafter, the membrane develops one or a series of slow hyperpolarizations before a final sustained membrane potential (E(s)) (mean -14 mV, range -5 to -40) is established. The mean value of the peak of the first hyperpolarization (E(h)) is -30 mV (range -10 to -55 mV). The initial fast peak transient, measured upon microelectrode entry, was first described and analyzed by Lassen et al. (Lassen, U.V., A.M. T. Nielson, L. Pape, and L. O. Simonsen, 1971, J. Membr. Biol. 6:269-288 for other change in the membrane potential from its real value before impalement to a sustained depolarized value. This was shown to be true for macrophages by two-electrode impalements of single cells. Values of E(p), E(n), E(h), E(s), and membrane resistance (R(m)) measured for the other macrophages were similar to those of P388D1. From these results we conclude that E(p) is a better estimate of the true membrane potential of macrophages than E(s), and that the slow hyperpolarizations upon impalement should be regarded as transient repolarizations back to the original membrane potentials. Thus, analysis of the initial fast impalement transient can be a valuable aid in the estimation of the membrane potential of various sorts of small isolated cells by microelectrodes. PMID:6833384

Abutment Disconnection/Reconnection Affects Peri-implant Marginal Bone Levels: A Meta-Analysis.

PubMed

Koutouzis, Theofilos; Gholami, Fatemeh; Reynolds, John; Lundgren, Tord; Kotsakis, Georgios A

Preclinical and clinical studies have shown that marginal bone loss can be secondary to repeated disconnection and reconnection of abutments that affect the peri-implant mucosal seal. The aim of this systematic review and meta-analysis was to evaluate the impact of abutment disconnections/reconnections on peri-implant marginal bone level changes. To address this question, two reviewers independently performed an electronic search of three major databases up to October 2015 complemented by manual searches. Eligible articles were selected on the basis of prespecified inclusion and exclusion criteria after a two-phase search strategy and assessed for risk of bias. A random-effects meta-analysis was performed for marginal bone loss. The authors initially identified 392 titles and abstracts. After evaluation, seven controlled clinical studies were included. Qualitative assessment of the articles revealed a trend toward protective marginal bone level preservation for implants with final abutment placement (FAP) at the time of implant placement compared with implants for which there were multiple abutment placements (MAP). The FAP group exhibited a marginal bone level change ranging from 0.08 to 0.34 mm, whereas the MAP group exhibited a marginal bone level change ranging from 0.09 to 0.55 mm. Meta-analysis of the seven studies reporting on 396 implants showed significantly greater bone loss in cases of multiple abutment disconnections/reconnections. The weighted mean difference in marginal bone loss was 0.19 mm (95% confidence interval, 0.06-0.32 mm), favoring bone preservation in the FAP group. Within the limitations of this meta-analysis, abutment disconnection and reconnection significantly affected peri-implant marginal bone levels. These findings pave the way for revisiting current restorative protocols at the restorative treatment planning stage to prevent incipient marginal bone loss.

O2 Plasma Etching and Antistatic Gun Surface Modifications for CNT Yarn Microelectrode Improve Sensitivity and Antifouling Properties.

PubMed

Yang, Cheng; Wang, Ying; Jacobs, Christopher B; Ivanov, Ilia N; Venton, B Jill

2017-05-16

Carbon nanotube (CNT) based microelectrodes exhibit rapid and selective detection of neurotransmitters. While different fabrication strategies and geometries of CNT microelectrodes have been characterized, relatively little research has investigated ways to selectively enhance their electrochemical properties. In this work, we introduce two simple, reproducible, low-cost, and efficient surface modification methods for carbon nanotube yarn microelectrodes (CNTYMEs): O 2 plasma etching and antistatic gun treatment. O 2 plasma etching was performed by a microwave plasma system with oxygen gas flow and the optimized time for treatment was 1 min. The antistatic gun treatment flows ions by the electrode surface; two triggers of the antistatic gun was the optimized number on the CNTYME surface. Current for dopamine at CNTYMEs increased 3-fold after O 2 plasma etching and 4-fold after antistatic gun treatment. When the two treatments were combined, the current increased 12-fold, showing the two effects are due to independent mechanisms that tune the surface properties. O 2 plasma etching increased the sensitivity due to increased surface oxygen content but did not affect surface roughness while the antistatic gun treatment increased surface roughness but not oxygen content. The effect of tissue fouling on CNT yarns was studied for the first time, and the relatively hydrophilic surface after O 2 plasma etching provided better resistance to fouling than unmodified or antistatic gun treated CNTYMEs. Overall, O 2 plasma etching and antistatic gun treatment improve the sensitivity of CNTYMEs by different mechanisms, providing the possibility to tune the CNTYME surface and enhance sensitivity.

High-performance and versatile electrochemical aptasensor based on self-supported nanoporous gold microelectrode and enzyme-induced signal amplification.

PubMed

Shi, Lei; Rong, Xiaojiao; Wang, Yan; Ding, Shiming; Tang, Wanying

2018-04-15

Herein, novel and versatile electrochemical aptasensors were constructed on a self-supported nanoporous gold (np-Au) microelectrode, integrating with an exonuclease III (Exo III) induced signal amplification strategy. Self-supported np-Au microelectrode with 3D bicontinuous nanoporous structures possesses tremendously large specific area, clean surface, high stability and biocompatibility, bringing about significant advantages in both molecular recognition and signal response. As paradigms, two analytes of bisphenol A (BPA) and ochratoxin A (OTA) were selected to demonstrate the superiority and versatility of designed aptasensors. Trace amounts of mDNA (associated with BPA or OTA concentration) hybridized with cDNA strands assembled on np-Au microelectrode, activating the cleavage reaction with Exo III. Thus, cDNA was digested and mDNA was released to undergo a new hybridization and cleavage cycle. Finally, residual cDNA strands were recognized by methylene blue labelled rDNA/AuNPs with the assistance of hDNA to generate the electrochemical signals, which were used to quantitatively monitor targets. Under the optimized conditions, prepared aptasensors exhibited wide linear ranges (25pg/mL to 2ng/mL for BPA, 10pg/mL to 5ng/mL for OTA) with ultralow detection limits (10pg/mL for BPA, 5pg/mL for OTA), excellent selectivity and stability, and reliable detection in real samples. This work opens a new horizon for constructing promising electrochemical aptasensors for environmental monitoring, medical diagnostics and food safety. Copyright © 2017 Elsevier B.V. All rights reserved.

A Wireless Headstage for Combined Optogenetics and Multichannel Electrophysiological Recording.

PubMed

Gagnon-Turcotte, Gabriel; LeChasseur, Yoan; Bories, Cyril; Messaddeq, Younes; De Koninck, Yves; Gosselin, Benoit

2017-02-01

This paper presents a wireless headstage with real-time spike detection and data compression for combined optogenetics and multichannel electrophysiological recording. The proposed headstage, which is intended to perform both optical stimulation and electrophysiological recordings simultaneously in freely moving transgenic rodents, is entirely built with commercial off-the-shelf components, and includes 32 recording channels and 32 optical stimulation channels. It can detect, compress and transmit full action potential waveforms over 32 channels in parallel and in real time using an embedded digital signal processor based on a low-power field programmable gate array and a Microblaze microprocessor softcore. Such a processor implements a complete digital spike detector featuring a novel adaptive threshold based on a Sigma-delta control loop, and a wavelet data compression module using a new dynamic coefficient re-quantization technique achieving large compression ratios with higher signal quality. Simultaneous optical stimulation and recording have been performed in-vivo using an optrode featuring 8 microelectrodes and 1 implantable fiber coupled to a 465-nm LED, in the somatosensory cortex and the Hippocampus of a transgenic mouse expressing ChannelRhodospin (Thy1::ChR2-YFP line 4) under anesthetized conditions. Experimental results show that the proposed headstage can trigger neuron activity while collecting, detecting and compressing single cell microvolt amplitude activity from multiple channels in parallel while achieving overall compression ratios above 500. This is the first reported high-channel count wireless optogenetic device providing simultaneous optical stimulation and recording. Measured characteristics show that the proposed headstage can achieve up to 100% of true positive detection rate for signal-to-noise ratio (SNR) down to 15 dB, while achieving up to 97.28% at SNR as low as 5 dB. The implemented prototype features a lifespan of up to 105 minutes, and uses a lightweight (2.8 g) and compact [Formula: see text] rigid-flex printed circuit board.

Hand posture classification using electrocorticography signals in the gamma band over human sensorimotor brain areas

NASA Astrophysics Data System (ADS)

Chestek, Cynthia A.; Gilja, Vikash; Blabe, Christine H.; Foster, Brett L.; Shenoy, Krishna V.; Parvizi, Josef; Henderson, Jaimie M.

2013-04-01

Objective. Brain-machine interface systems translate recorded neural signals into command signals for assistive technology. In individuals with upper limb amputation or cervical spinal cord injury, the restoration of a useful hand grasp could significantly improve daily function. We sought to determine if electrocorticographic (ECoG) signals contain sufficient information to select among multiple hand postures for a prosthetic hand, orthotic, or functional electrical stimulation system.Approach. We recorded ECoG signals from subdural macro- and microelectrodes implanted in motor areas of three participants who were undergoing inpatient monitoring for diagnosis and treatment of intractable epilepsy. Participants performed five distinct isometric hand postures, as well as four distinct finger movements. Several control experiments were attempted in order to remove sensory information from the classification results. Online experiments were performed with two participants. Main results. Classification rates were 68%, 84% and 81% for correct identification of 5 isometric hand postures offline. Using 3 potential controls for removing sensory signals, error rates were approximately doubled on average (2.1×). A similar increase in errors (2.6×) was noted when the participant was asked to make simultaneous wrist movements along with the hand postures. In online experiments, fist versus rest was successfully classified on 97% of trials; the classification output drove a prosthetic hand. Online classification performance for a larger number of hand postures remained above chance, but substantially below offline performance. In addition, the long integration windows used would preclude the use of decoded signals for control of a BCI system. Significance. These results suggest that ECoG is a plausible source of command signals for prosthetic grasp selection. Overall, avenues remain for improvement through better electrode designs and placement, better participant training, and characterization of non-stationarities such that ECoG could be a viable signal source for grasp control for amputees or individuals with paralysis.

Microstimulation of the lumbar DRG recruits primary afferent neurons in localized regions of lower limb.

PubMed

Ayers, Christopher A; Fisher, Lee E; Gaunt, Robert A; Weber, Douglas J

2016-07-01

Patterned microstimulation of the dorsal root ganglion (DRG) has been proposed as a method for delivering tactile and proprioceptive feedback to amputees. Previous studies demonstrated that large- and medium-diameter afferent neurons could be recruited separately, even several months after implantation. However, those studies did not examine the anatomical localization of sensory fibers recruited by microstimulation in the DRG. Achieving precise recruitment with respect to both modality and receptive field locations will likely be crucial to create a viable sensory neuroprosthesis. In this study, penetrating microelectrode arrays were implanted in the L5, L6, and L7 DRG of four isoflurane-anesthetized cats instrumented with nerve cuff electrodes around the proximal and distal branches of the sciatic and femoral nerves. A binary search was used to find the recruitment threshold for evoking a response in each nerve cuff. The selectivity of DRG stimulation was characterized by the ability to recruit individual distal branches to the exclusion of all others at threshold; 84.7% (n = 201) of the stimulation electrodes recruited a single nerve branch, with 9 of the 15 instrumented nerves recruited selectively. The median stimulation threshold was 0.68 nC/phase, and the median dynamic range (increase in charge while stimulation remained selective) was 0.36 nC/phase. These results demonstrate the ability of DRG microstimulation to achieve selective recruitment of the major nerve branches of the hindlimb, suggesting that this approach could be used to drive sensory input from localized regions of the limb. This sensory input might be useful for restoring tactile and proprioceptive feedback to a lower-limb amputee. Copyright © 2016 the American Physiological Society.

Coating flexible probes with an ultra fast degrading polymer to aid in tissue insertion

PubMed Central

Wang, Shuwu; Singh, Sagar; Damodaran, Vinod B.; Kaplan, Hilton M.; Kohn, Joachim; Shreiber, David I.; Zahn, Jeffrey D.

2016-01-01

We report a fabrication process for coating neural probes with an ultrafast degrading polymer to create consistent and reproducible devices for neural tissue insertion. The rigid polymer coating acts as a probe insertion aid, but resorbs within hours post-implantation. Despite the feasibility for short term neural recordings from currently available neural prosthetic devices, most of these devices suffer from long term gliosis, which isolates the probes from adjacent neurons, increasing the recording impedance and stimulation threshold. The size and stiffness of implanted probes have been identified as critical factors that lead to this long term gliosis. Smaller, more flexible probes that match the mechanical properties of brain tissue could allow better long term integration by limiting the mechanical disruption of the surrounding tissue during and after probe insertion, while being flexible enough to deform with the tissue during brain movement. However, these small flexible probes inherently lack the mechanical strength to penetrate the brain on their own. In this work, we have developed a micromolding method for coating a non-functional miniaturized SU-8 probe with an ultrafast degrading tyrosine-derived polycarbonate (E5005(2K)). Coated, non-functionalized probes of varying dimensions were reproducibly fabricated with high yields. The polymer erosion/degradation profiles of the probes were characterized in vitro. The probes were also mechanically characterized in ex vivo brain tissue models by measuring buckling and insertion forces during probe insertion. The results demonstrate the ability to produce polymer coated probes of consistent quality for future in vivo use, for example to study the effects of different design parameters that may affect tissue response during long term chronic intra-cortical microelectrode neural recordings. PMID:25681971

CranialVault and its CRAVE tools: a clinical computer assistance system for deep brain stimulation (DBS) therapy.

PubMed

D'Haese, Pierre-François; Pallavaram, Srivatsan; Li, Rui; Remple, Michael S; Kao, Chris; Neimat, Joseph S; Konrad, Peter E; Dawant, Benoit M

2012-04-01

A number of methods have been developed to assist surgeons at various stages of deep brain stimulation (DBS) therapy. These include construction of anatomical atlases, functional databases, and electrophysiological atlases and maps. But, a complete system that can be integrated into the clinical workflow has not been developed. In this paper we present a system designed to assist physicians in pre-operative target planning, intra-operative target refinement and implantation, and post-operative DBS lead programming. The purpose of this system is to centralize the data acquired a the various stages of the procedure, reduce the amount of time needed at each stage of the therapy, and maximize the efficiency of the entire process. The system consists of a central repository (CranialVault), of a suite of software modules called CRAnialVault Explorer (CRAVE) that permit data entry and data visualization at each stage of the therapy, and of a series of algorithms that permit the automatic processing of the data. The central repository contains image data for more than 400 patients with the related pre-operative plans and position of the final implants and about 10,550 electrophysiological data points (micro-electrode recordings or responses to stimulations) recorded from 222 of these patients. The system has reached the stage of a clinical prototype that is being evaluated clinically at our institution. A preliminary quantitative validation of the planning component of the system performed on 80 patients who underwent the procedure between January 2009 and December 2009 shows that the system provides both timely and valuable information. Copyright © 2010 Elsevier B.V. All rights reserved.

Coating flexible probes with an ultra fast degrading polymer to aid in tissue insertion.

PubMed

Lo, Meng-chen; Wang, Shuwu; Singh, Sagar; Damodaran, Vinod B; Kaplan, Hilton M; Kohn, Joachim; Shreiber, David I; Zahn, Jeffrey D

2015-04-01

We report a fabrication process for coating neural probes with an ultrafast degrading polymer to create consistent and reproducible devices for neural tissue insertion. The rigid polymer coating acts as a probe insertion aid, but resorbs within hours post-implantation. Despite the feasibility for short term neural recordings from currently available neural prosthetic devices, most of these devices suffer from long term gliosis, which isolates the probes from adjacent neurons, increasing the recording impedance and stimulation threshold. The size and stiffness of implanted probes have been identified as critical factors that lead to this long term gliosis. Smaller, more flexible probes that match the mechanical properties of brain tissue could allow better long term integration by limiting the mechanical disruption of the surrounding tissue during and after probe insertion, while being flexible enough to deform with the tissue during brain movement. However, these small flexible probes inherently lack the mechanical strength to penetrate the brain on their own. In this work, we have developed a micromolding method for coating a non-functional miniaturized SU-8 probe with an ultrafast degrading tyrosine-derived polycarbonate (E5005(2K)). Coated, non-functionalized probes of varying dimensions were reproducibly fabricated with high yields. The polymer erosion/degradation profiles of the probes were characterized in vitro. The probes were also mechanically characterized in ex vivo brain tissue models by measuring buckling and insertion forces during probe insertion. The results demonstrate the ability to produce polymer coated probes of consistent quality for future in vivo use, for example to study the effects of different design parameters that may affect tissue response during long term chronic intra-cortical microelectrode neural recordings.

Nuclear reaction analysis of Ge ion-implanted ZnO bulk single crystals: The evaluation of the displacement in oxygen lattices

NASA Astrophysics Data System (ADS)

Kamioka, K.; Oga, T.; Izawa, Y.; Kuriyama, K.; Kushida, K.; Kinomura, A.

2014-08-01

The displacement of oxygen lattices in Ge ion-implanted ZnO bulk single crystals is studied by nuclear reaction analysis (NAR), photoluminescence (PL), and Van der Pauw methods. The Ge ion-implantation (net concentration: 2.6 × 1020 cm-3) into ZnO is performed using a multiple-step energy. The high resistivity of ∼103 Ω cm in un-implanted samples remarkably decreased to ∼10-2 Ω cm after implanting Ge-ion and annealing subsequently. NRA measurements of as-implanted and annealed samples suggest the existence of the lattice displacement of O atoms acting as acceptor defects. As O related defects still remain after annealing, these defects are not attributed to the origin of the low resistivity in 800 and 1000 °C annealed ZnO.

Optical power transfer and communication methods for wireless implantable sensing platforms.

PubMed

Mujeeb-U-Rahman, Muhammad; Adalian, Dvin; Chang, Chieh-Feng; Scherer, Axel

2015-09-01

Ultrasmall scale implants have recently attracted focus as valuable tools for monitoring both acute and chronic diseases. Semiconductor optical technologies are the key to miniaturizing these devices to the long-sought sub-mm scale, which will enable long-term use of these devices for medical applications. This can also enable the use of multiple implantable devices concurrently to form a true body area network of sensors. We demonstrate optical power transfer techniques and methods to effectively harness this power for implantable devices. Furthermore, we also present methods for optical data transfer from such implants. Simultaneous use of these technologies can result in miniaturized sensing platforms that can allow for large-scale use of such systems in real world applications.

Polymeric Packaging for Fully Implantable Wireless Neural Microsensors

PubMed Central

Aceros, Juan; Yin, Ming; Borton, David A.; Patterson, William R.; Bull, Christopher; Nurmikko, Arto V.

2014-01-01

We present polymeric packaging methods used for subcutaneous, fully implantable, broadband, and wireless neurosensors. A new tool for accelerated testing and characterization of biocompatible polymeric packaging materials and processes is described along with specialized test units to simulate our fully implantable neurosensor components, materials and fabrication processes. A brief description of the implantable systems is presented along with their current encapsulation methods based on polydimethylsiloxane (PDMS). Results from in-vivo testing of multiple implanted neurosensors in swine and non-human primates are presented. Finally, a novel augmenting polymer thin film material to complement the currently employed PDMS is introduced. This thin layer coating material is based on the Plasma Enhanced Chemical Vapor Deposition (PECVD) process of Hexamethyldisiloxane (HMDSO) and Oxygen (O2). PMID:23365999

The power of sound: miniaturized medical implants with ultrasonic links

NASA Astrophysics Data System (ADS)

Wang, Max L.; Chang, Ting Chia; Charthad, Jayant; Weber, Marcus J.; Arbabian, Amin

2017-05-01

Miniaturized wirelessly powered implants capable of operating and communicating deep in the body are necessary for the next-generation of diagnostics and therapeutics. A major challenge in developing these minimally invasive implants is the tradeoff between device size, functionality, and operating depth. Here, we review two different wireless powering methods, inductive and ultrasonic power transfer, examine how to analyze their power transfer efficiency, and evaluate their potential for powering implantable medical devices. In particular, we show how ultrasonic wireless power transfer can address these challenges due to its safety, low attenuation, and millimeter wavelengths in the body. Finally, we demonstrate two ultrasonically powered implants capable of active power harvesting and bidirectional communication for closed-loop operation while functioning through multiple centimeters of tissue.

Optical power transfer and communication methods for wireless implantable sensing platforms

NASA Astrophysics Data System (ADS)

Mujeeb-U-Rahman, Muhammad; Adalian, Dvin; Chang, Chieh-Feng; Scherer, Axel

2015-09-01

Ultrasmall scale implants have recently attracted focus as valuable tools for monitoring both acute and chronic diseases. Semiconductor optical technologies are the key to miniaturizing these devices to the long-sought sub-mm scale, which will enable long-term use of these devices for medical applications. This can also enable the use of multiple implantable devices concurrently to form a true body area network of sensors. We demonstrate optical power transfer techniques and methods to effectively harness this power for implantable devices. Furthermore, we also present methods for optical data transfer from such implants. Simultaneous use of these technologies can result in miniaturized sensing platforms that can allow for large-scale use of such systems in real world applications.

A computational model for estimating recruitment of primary afferent fibers by intraneural stimulation in the dorsal root ganglia

NASA Astrophysics Data System (ADS)

Bourbeau, D. J.; Hokanson, J. A.; Rubin, J. E.; Weber, D. J.

2011-10-01

Primary afferent microstimulation has been proposed as a method for activating cutaneous and muscle afferent fibers to restore tactile and proprioceptive feedback after limb loss or peripheral neuropathy. Large populations of primary afferent fibers can be accessed directly by implanting microelectrode arrays in the dorsal root ganglia (DRG), which provide a compact and stable target for stimulating a diverse group of sensory fibers. To gain insight into factors affecting the number and types of primary afferents activated, we developed a computational model that simulates the recruitment of fibers in the feline L7 DRG. The model comprises two parts. The first part is a single-fiber model used to describe the current-distance relation and was based on the McIntyre-Richardson-Grill model for excitability. The second part uses the results of the singe-fiber model and published data on fiber size distributions to predict the probability of recruiting a given number of fibers as a function of stimulus intensity. The range of intensities over which exactly one fiber was recruited was approximately 0.5-5 µA (0.1-1 nC per phase); the stimulus intensity at which the probability of recruiting exactly one fiber was maximized was 2.3 µA. However, at 2.3 µA, it was also possible to recruit up to three fibers, albeit with a lower probability. Stimulation amplitudes up to 6 µA were tested with the population model, which showed that as the amplitude increased, the number of fibers recruited increased exponentially. The distribution of threshold amplitudes predicted by the model was similar to that previously reported by in vivo experimentation. Finally, the model suggested that medium diameter fibers (7.3-11.5 µm) may be recruited with much greater probability than large diameter fibers (12.8-16 µm). This model may be used to efficiently test a range of stimulation parameters and nerve morphologies to complement results from electrophysiology experiments and to aid in the design of microelectrode arrays for neural interfaces.

Electrochemical Activation of Diamond Microelectrodes: Implications for the In Vitro Measurement of Serotonin in the Bowel

PubMed Central

Duran, Boris; Brocenschi, Ricardo F.; France, Marion; Galligan, James J.; Swain, Greg M.

2014-01-01

The electrochemical pretreatment of diamond microelectrodes was investigated for the purpose of learning how an anodic, cathodic or a combined anodic + cathodic polarization affects the charge-transfer kinetics for two surface-sensitive redox systems: ferri/ferrocyanide and serotonin (5-hydroxytryptamine, 5-HT). The pretreatments were performed in 0.5 mol L−1 H2SO4. The anodic pretreatment was performed galvanically for 30 s at 250 mA cm−2. The 10 cathodic pretreatment was performed for 180 s at −250 mA cm−2. The combined pretreatment involved application of the anodic step first followed by the cathodic step. The results clearly demonstrate that the best performance for both redox systems is obtained after the cathodic polarization, which presumably activates the electrode by cleaning the surface and removing site-blocking surface carbon-oxygen functionalities. The cathodic pretreatment was found to be effective at activating a fouled microelectrode in situ. This observation has important implication for the measurement of 5-HT in the bowel. PMID:24802953

All-Diamond Microelectrodes as Solid State Probes for Localized Electrochemical Sensing.

PubMed

Silva, Eduardo L; Gouvêa, Cristol P; Quevedo, Marcela C; Neto, Miguel A; Archanjo, Braulio S; Fernandes, António J S; Achete, Carlos A; Silva, Rui F; Zheludkevich, Mikhail L; Oliveira, Filipe J

2015-07-07

The fabrication of an all-diamond microprobe is demonstrated for the first time. This ME (microelectrode) assembly consists of an inner boron doped diamond (BDD) layer and an outer undoped diamond layer. Both layers were grown on a sharp tungsten tip by chemical vapor deposition (CVD) in a stepwise manner within a single deposition run. BDD is a material with proven potential as an electrochemical sensor. Undoped CVD diamond is an insulating material with superior chemical stability in comparison to conventional insulators. Focused ion beam (FIB) cutting of the apex of the ME was used to expose an electroactive BDD disk. By cyclic voltammetry, the redox reaction of ferrocenemethanol was shown to take place at the BDD microdisk surface. In order to ensure that the outer layer was nonelectrically conductive, a diffusion barrier for boron atoms was established seeking the formation of boron-hydrogen complexes at the interface between the doped and the undoped diamond layers. The applicability of the microelectrodes in localized corrosion was demonstrated by scanning amperometric measurements of oxygen distribution above an Al-Cu-CFRP (Carbon Fiber Reinforced Polymer) galvanic corrosion cell.

Microfluidic Arrayed Lab-On-A-Chip for Electrochemical Capacitive Detection of DNA Hybridization Events.

PubMed

Ben-Yoav, Hadar; Dykstra, Peter H; Bentley, William E; Ghodssi, Reza

2017-01-01

A microfluidic electrochemical lab-on-a-chip (LOC) device for DNA hybridization detection has been developed. The device comprises a 3 × 3 array of microelectrodes integrated with a dual layer microfluidic valved manipulation system that provides controlled and automated capabilities for high throughput analysis of microliter volume samples. The surface of the microelectrodes is functionalized with single-stranded DNA (ssDNA) probes which enable specific detection of complementary ssDNA targets. These targets are detected by a capacitive technique which measures dielectric variation at the microelectrode-electrolyte interface due to DNA hybridization events. A quantitative analysis of the hybridization events is carried out based on a sensing modeling that includes detailed analysis of energy storage and dissipation components. By calculating these components during hybridization events the device is able to demonstrate specific and dose response sensing characteristics. The developed microfluidic LOC for DNA hybridization detection offers a technology for real-time and label-free assessment of genetic markers outside of laboratory settings, such as at the point-of-care or in-field environmental monitoring.

Inkjet-printed microelectrodes on PDMS as biosensors for functionalized microfluidic systems.

PubMed

Wu, Jianwei; Wang, Ridong; Yu, Haixia; Li, Guijun; Xu, Kexin; Tien, Norman C; Roberts, Robert C; Li, Dachao

2015-02-07

Microfluidic systems based on polydimethylsiloxane (PDMS) have gained popularity in recent years. However, microelectrode patterning on PDMS to form biosensors in microchannels remains a worldwide technical issue due to the hydrophobicity of PDMS and its weak adhesion to metals. In this study, an additive technique using inkjet-printed silver nanoparticles to form microelectrodes on PDMS is presented. (3-Mercaptopropyl)trimethoxysilane (MPTMS) was used to modify the surface of PDMS to improve its surface wettability and its adhesion to silver. The modified surface of PDMS is rendered relatively hydrophilic, which is beneficial for the silver droplets to disperse and thus effectively avoids the coalescence of adjacent droplets. Additionally, a multilevel matrix deposition (MMD) method is used to further avoid the coalescence and yield a homogeneous pattern on the MPTMS-modified PDMS. A surface wettability comparison and an adhesion test were conducted. The resulting silver pattern exhibited good uniformity, conductivity and excellent adhesion to PDMS. A three-electrode electrochemical biosensor was fabricated successfully using this method and sealed in a PDMS microchannel, forming a lab-on-a-chip glucose biosensing system.

Nanostructured gold microelectrodes for extracellular recording from electrogenic cells.

PubMed

Brüggemann, D; Wolfrum, B; Maybeck, V; Mourzina, Y; Jansen, M; Offenhäusser, A

2011-07-01

We present a new biocompatible nanostructured microelectrode array for extracellular signal recording from electrogenic cells. Microfabrication techniques were combined with a template-assisted approach using nanoporous aluminum oxide to develop gold nanopillar electrodes. The nanopillars were approximately 300-400 nm high and had a diameter of 60 nm. Thus, they yielded a higher surface area of the electrodes resulting in a decreased impedance compared to planar electrodes. The interaction between the large-scale gold nanopillar arrays and cardiac muscle cells (HL-1) was investigated via focused ion beam milling. In the resulting cross-sections we observed a tight coupling between the HL-1 cells and the gold nanostructures. However, the cell membranes did not bend into the cleft between adjacent nanopillars due to the high pillar density. We performed extracellular potential recordings from HL-1 cells with the nanostructured microelectrode arrays. The maximal amplitudes recorded with the nanopillar electrodes were up to 100% higher than those recorded with planar gold electrodes. Increasing the aspect ratio of the gold nanopillars and changing the geometrical layout can further enhance the signal quality in the future.

A fast stimulability screening protocol for neuronal cultures on microelectrode arrays.

PubMed

Kapucu, Fikret E; Tanskanen, Jarno M A; Yuan, Yuting; Hyttinen, Jari A K

2015-01-01

Microelectrode arrays (MEAs) are used to study the electrical activity in brain slices and neuronal cultures. MEA experiments for the analysis of electrical stimulation responses require the tissue or culture to be prone to stimulation. For brain slices, potential stimulation sites may be directly visible in microscope, in which case the determination of stimulability at those locations is sufficient. In unstructured neuronal cultures, potential stimulation sites may not be known a priori, and spatial stimulability screening should be performed. Considering, e.g., 59 microelectrode sites, each to be stimulated several times, may result in long screening times, unacceptable with a MEA system without an integrated CO2 incubator, or in high stimulation effects on the networks. Here, we describe an implementation of a fast stimulation protocol employing pseudorandom stimulation site switching aiming at alleviating the network effects of the stimulability screening. In this paper, we show the usability of the proposed protocol by first detecting stimulable locations and subsequently apply repeated stimulation on the identified potentially stimulable locations to observe an exemplary neuronal pathway.

Fabrication of two-layer poly(dimethyl siloxane) devices for hydrodynamic cell trapping and exocytosis measurement with integrated indium tin oxide microelectrodes arrays

PubMed Central

Gao, Changlu; Sun, Xiuhua; Gillis, Kevin D.

2016-01-01

The design, fabrication and test of a microfluidic cell trapping device to measure single cell exocytosis were reported. Research on the patterning of double layer template based on repetitive standard photolithography of AZ photoresist was investigated. The replicated poly(dimethyl siloxane) devices with 2.5 μm deep channels were proved to be efficient for stopping cells. Quantal exocytosis measurement can be achieved by targeting single or small clumps of chromaffin cells on top of the 10 μm ×10 μm indium tin oxide microelectrodes arrays with the developed microdevice. And about 72% of the trapping sites can be occupied by cells with hydrodynamic trapping method and the recorded amperometric signals are comparable to the results with traditional carbon fiber microelectrodes. The method of manufacturing the microdevices is simple, low-cost and easy to perform. The manufactured device offers a platform for the high throughput detection of quantal catecholamine exocytosis from chromaffin cells with sufficient sensitivity and broad application. PMID:23329291

Neuronal ensemble control of prosthetic devices by a human with tetraplegia

NASA Astrophysics Data System (ADS)

Hochberg, Leigh R.; Serruya, Mijail D.; Friehs, Gerhard M.; Mukand, Jon A.; Saleh, Maryam; Caplan, Abraham H.; Branner, Almut; Chen, David; Penn, Richard D.; Donoghue, John P.

2006-07-01

Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a `neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.

Methods for Surgical Targeting of the STN in Early-Stage Parkinson’s Disease

PubMed Central

Camalier, Corrie R.; Konrad, Peter E.; Gill, Chandler E.; Kao, Chris; Remple, Michael R.; Nasr, Hana M.; Davis, Thomas L.; Hedera, Peter; Phibbs, Fenna T.; Molinari, Anna L.; Neimat, Joseph S.; Charles, David

2013-01-01

Patients with Parkinson’s disease (PD) experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN) with surgical access. While locating STN in advanced disease patients (Hoehn–Yahr Stage III or IV) is well understood and routinely performed at many centers in the context of deep brain stimulation surgery, the ability to identify this nucleus in early-stage patients has not previously been explored in a sizeable cohort. We report surgical methods used to target the STN in 15 patients with early PD (Hoehn–Yahr Stage II), using a combination of image guided surgery, microelectrode recordings, and clinical responses to macrostimulation of the region surrounding the STN. Measures of electrophysiology (firing rates and root mean squared activity) have previously been found to be lower than in later-stage patients, however, the patterns of electrophysiology seen and dopamimetic macrostimulation effects are qualitatively similar to those seen in advanced stages. Our experience with surgical implantation of Parkinson’s patients with minimal motor symptoms suggest that it remains possible to accurately target the STN in early-stage PD using traditional methods. PMID:24678307

Development path and current status of the NANIVID: a new device for cancer cell studies.

PubMed

Raja, Waseem Khan; Padgen, Michael R; Williams, James K; Gertler, Frank B; Wyckoff, Jeffrey B; Condeelis, John S; Castracane, James

2012-03-29

Cancer cells create a unique microenvironment in vivo that enables migration to distant organs. To better understand the tumor micro-environment, special tools and devices are required to monitor the interactions between different cell types and the effects of particular chemical gradients. Our study presents the design and optimization of a versatile chemotaxis device, the nano-intravital device (NANIVID), which consists of etched and bonded glass substrates that create a soluble factor reservoir. The device contains a customized hydrogel blend that is loaded with epidermal growth factor (EGF), which diffuses from the outlet to create a chemotactic gradient that can be sustained for many hours in order to attract specific cells to the device. A microelectrode array is under development for quantification of cell collection and will be incorporated into future device generations. Additionally, the NANIVID can be modified to generate gradients of other soluble factors in order to initiate controlled changes to the microenvironment including the induction of hypoxia, manipulation of extracellular matrix stiffness, etc. The focus of the article is to present the design and optimization of the device towards wide ranging applications of cancer cell dynamics in vitro and, ultimately, implantation for in vivo investigations.

Engineering of Neuron Growth and Enhancing Cell-Chip Communication via Mixed SAMs.

PubMed

Markov, Aleksandr; Maybeck, Vanessa; Wolf, Nikolaus; Mayer, Dirk; Offenhäusser, Andreas; Wördenweber, Roger

2018-06-06

The interface between cells and inorganic surfaces represents one of the key elements for bioelectronics experiments and applications ranging from cell cultures and bioelectronics devices to medical implants. In the present paper, we describe a way to tailor the biocompatibility of substrates in terms of cell growth and to significantly improve cell-chip communication, and we also demonstrate the reusability of the substrates for cell experiments. All these improvements are achieved by coating the substrates or chips with a self-assembled monolayer (SAM) consisting of a mixture of organic molecules, (3-aminopropyl)-triethoxysilane and (3-glycidyloxypropyl)-trimethoxysilane. By varying the ratio of these molecules, we are able to tune the cell density and live/dead ratios of rat cortical neurons cultured directly on the mixed SAM as well as neurons cultured on protein-coated SAMs. Furthermore, the use of the SAM leads to a significant improvement in cell-chip communications. Action potential signals of up to 9.4 ± 0.6 mV (signal-to-noise ratio up to 47) are obtained for HL-1 cells on microelectrode arrays. Finally, we demonstrate that the SAMs facilitate a reusability of the samples for all cell experiments with little re-processing.

[Artificial vision for the human blind].

PubMed

Ortigoza-Ayala, Luis Octavio; Ruiz-Huerta, Leopoldo; Caballero-Ruiz, Alberto; Kussul, Ernst

2009-01-01

Since 1960 many attempts have been made to develop visual prostheses for the blind; most of the devices based on the production of phosphenes through electrical stimulation with microelectrodes at the retina, optic nerve, lateral geniculate or occipital lobe are incapable to reconstruct a coherent retinotopic map (coordinate match between the image and the visual perception of the patient); furthermore they display important restrictions at the biomaterial level that hinder their final implantation through surgical techniques which at present time offers more risks than benefits to the patient. Considering the new theories about intermodal perception it is possible the acquisition of visual information through other senses; The Micromechanics and Mecatronics Group (GMM) from The Center of Applied Sciences and Technological Development at The National Autonomous University of Mexico by this paper, describes the experimental design and psychophysical data necessary for the construction of a visual sensory substitution prostheses with a vibrotactile system. The vibrotactile mechanism locates different bars over the epidermis in a predetermined way to reproduce a point by point matrix order in a logical sequence of rows and columns that allow the construction of an image with an external device that not require invasive procedures.

Miniaturized optoelectronic system for telemetry of in vivo voltammetric signals.

PubMed

De Simoni, M G; De Luigi, A; Imeri, L; Algeri, S

1990-08-01

In vivo voltammetry is an electrochemical technique that uses carbon fiber microelectrodes stereotaxically implanted in brain areas to monitor monoamine metabolism and release continuously, in freely moving animals. Electric wires connect the polarograph to the animal. A wire-less transmission system (optoelectronic transmission, OPT) of voltammetric signals is described here. It uses infrared diffused light, exploiting the diffusion of the transmitted light over walls and ceiling towards a receiver. The transmission system consists of a main unit and a satellite unit (40 x 30 x 5 mm) positioned on the animal's back. Voltammetric recordings obtained by the classical system (with wires) and by OPT are well defined and almost identical in shape. The power supply is provided by two thin lithium batteries (+/- 3V) that can record for up to 20 h. OPT permits detailed behavioral observations since the animal can be left free to move in a spacious environment. Voltammetry using OPT allows simultaneous recording of neuronal firing activity as well as electroencephalographic recordings (EEG) since there is no cross-talk between the circuits used. The results illustrate the reliability and usefulness of this wire-less transmission system for studying relationships between neurochemical, behavioral and electrophysiological activities.

Techniques for extracting single-trial activity patterns from large-scale neural recordings

PubMed Central

Churchland, Mark M; Yu, Byron M; Sahani, Maneesh; Shenoy, Krishna V

2008-01-01

Summary Large, chronically-implanted arrays of microelectrodes are an increasingly common tool for recording from primate cortex, and can provide extracellular recordings from many (order of 100) neurons. While the desire for cortically-based motor prostheses has helped drive their development, such arrays also offer great potential to advance basic neuroscience research. Here we discuss the utility of array recording for the study of neural dynamics. Neural activity often has dynamics beyond that driven directly by the stimulus. While governed by those dynamics, neural responses may nevertheless unfold differently for nominally identical trials, rendering many traditional analysis methods ineffective. We review recent studies – some employing simultaneous recording, some not – indicating that such variability is indeed present both during movement generation, and during the preceding premotor computations. In such cases, large-scale simultaneous recordings have the potential to provide an unprecedented view of neural dynamics at the level of single trials. However, this enterprise will depend not only on techniques for simultaneous recording, but also on the use and further development of analysis techniques that can appropriately reduce the dimensionality of the data, and allow visualization of single-trial neural behavior. PMID:18093826

LPA3-mediated lysophosphatidic acid signalling in implantation and embryo spacing

PubMed Central

Ye, Xiaoqin; Hama, Kotaro; Contos, James J.A.; Anliker, Brigitte; Inoue, Aska; Skinner, Michael K.; Suzuki, Hiroshi; Amano, Tomokazu; Kennedy, Grace; Arai, Hiroyuki; Aoki, Junken; Chun, Jerold

2005-01-01

Every successful pregnancy requires proper embryo implantation. Low implantation rate is a major problem during infertility treatments using assisted reproductive technologies (ART) 1. Here we report a new molecular influence on implantation through the lysophosphatidic acid (LPA) receptor LPA3 2–4. Targeted deletion of LPA3 in mice resulted in significantly reduced litter size, which could be attributed to delayed implantation and altered embryo spacing. These two events led to delayed embryonic development, hypertrophic placentas shared by multiple embryos, and embryonic death. An enzyme demonstrated to influence implantation, cyclooxygenase-2 (COX-2) 5, was down-regulated in LPA3-deficient uteri during preimplantation. Down regulation of COX-2 led to reduced levels of prostaglandins that are critical for implantation 1. Exogenous administration of the prostaglandins PGE2 and cPGI into LPA3-deficient females rescued delayed implantation but did not rescue defects in embryo spacing. These data identify LPA3 receptor-mediated signalling as a new influence on implantation and further indicate linkage between LPA signalling and prostaglandin biosynthesis. PMID:15875025

Imaging of enzyme activity using bio-LSI system enables simultaneous immunosensing of different analytes in multiple specimens.

PubMed

Hokuto, Toshiki; Yasukawa, Tomoyuki; Kunikata, Ryota; Suda, Atsushi; Inoue, Kumi Y; Ino, Kosuke; Matsue, Tomokazu; Mizutani, Fumio

2016-06-01

Electrochemical imaging is an excellent technique to characterize an activity of biomaterials, such as enzymes and cells. Large scale integration-based amperometric sensor (Bio-LSI) has been developed for the simultaneous and continuous detection of the concentration distribution of redox species generated by reactions of biomolecules. In this study, the Bio-LSI system was demonstrated to be applicable for simultaneous detection of different anaytes in multiple specimens. The multiple specimens containing human immunoglobulin G (hIgG) and mouse IgG (mIgG) were introduced into each channel of the upper substrate across the antibody lines for hIgG and mIgG on the lower substrate. Hydrogen peroxide generated by the enzyme reaction of glucose oxidase captured at intersections was simultaneously detected by 400 microelectrodes of Bio-LSI chip. The oxidation current increased with increasing the concentrations of hIgG, which can be detected in the range of 0.01-1.0 µg mL(-1) . Simultaneous detection of hIgG and mIgG in multiple specimens was achieved by using line pattern of both antibodies. Therefore, the presence of different target molecules in the multiple samples would be quantitatively and simultaneously visualized as a current image by the Bio-LSI system. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cardiotoxicity screening: a review of rapid-throughput in vitro approaches.

PubMed

Li, Xichun; Zhang, Rui; Zhao, Bin; Lossin, Christoph; Cao, Zhengyu

2016-08-01

Cardiac toxicity represents one of the leading causes of drug failure along different stages of drug development. Multiple very successful pharmaceuticals had to be pulled from the market or labeled with strict usage warnings due to adverse cardiac effects. In order to protect clinical trial participants and patients, the International Conference on Harmonization published guidelines to recommend that all new drugs to be tested preclinically for hERG (Kv11.1) channel sensitivity before submitting for regulatory reviews. However, extensive studies have demonstrated that measurement of hERG activity has limitations due to the multiple molecular targets of drug compound through which it may mitigate or abolish a potential arrhythmia, and therefore, a model measuring multiple ion channel effects is likely to be more predictive. Several phenotypic rapid-throughput methods have been developed to predict the potential cardiac toxic compounds in the early stages of drug development using embryonic stem cells- or human induced pluripotent stem cell-derived cardiomyocytes. These rapid-throughput methods include microelectrode array-based field potential assay, impedance-based or Ca(2+) dynamics-based cardiomyocytes contractility assays. This review aims to discuss advantages and limitations of these phenotypic assays for cardiac toxicity assessment.

Quantitative analysis of titanium-induced artifacts and correlated factors during micro-CT scanning.

PubMed

Li, Jun Yuan; Pow, Edmond Ho Nang; Zheng, Li Wu; Ma, Li; Kwong, Dora Lai Wan; Cheung, Lim Kwong

2014-04-01

To investigate the impact of cover screw, resin embedment, and implant angulation on artifact of microcomputed tomography (micro-CT) scanning for implant. A total of twelve implants were randomly divided into 4 groups: (i) implant only; (ii) implant with cover screw; (iii) implant with resin embedment; and (iv) implants with cover screw and resin embedment. Implants angulation at 0°, 45°, and 90° were scanned by micro-CT. Images were assessed, and the ratio of artifact volume to total volume (AV/TV) was calculated. A multiple regression analysis in stepwise model was used to determine the significance of different factors. One-way ANOVA was performed to identify which combination of factors could minimize the artifact. In the regression analysis, implant angulation was identified as the best predictor for artifact among the factors (P < 0.001). Resin embedment also had significant effect on artifact volume (P = 0.028), while cover screw had not (P > 0.05). Non-embedded implants with the axis parallel to X-ray source of micro-CT produced minimal artifact. Implant angulation and resin embedment affected the artifact volume of micro-CT scanning for implant, while cover screw did not. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cryogenic ion implantation near amorphization threshold dose for halo/extension junction improvement in sub-30 nm device technologies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Hugh; Todorov, Stan; Colombeau, Benjamin

2012-11-06

We report on junction advantages of cryogenic ion implantation with medium current implanters. We propose a methodical approach on maximizing cryogenic effects on junction characteristics near the amorphization threshold doses that are typically used for halo implants for sub-30 nm technologies. BF{sub 2}{sup +} implant at a dose of 8 Multiplication-Sign 10{sup 13}cm{sup -2} does not amorphize silicon at room temperature. When implanted at -100 Degree-Sign C, it forms a 30 - 35 nm thick amorphous layer. The cryogenic BF{sub 2}{sup +} implant significantly reduces the depth of the boron distribution, both as-implanted and after anneals, which improves short channelmore » rolloff characteristics. It also creates a shallower n{sup +}-p junction by steepening profiles of arsenic that is subsequently implanted in the surface region. We demonstrate effects of implant sequences, germanium preamorphization, indium and carbon co-implants for extension/halo process integration. When applied to sequences such as Ge+As+C+In+BF{sub 2}{sup +}, the cryogenic implants at -100 Degree-Sign C enable removal of Ge preamorphization, and form more active n{sup +}-p junctions and steeper B and In halo profiles than sequences at room temperature.« less

Esthetic evaluation of single-tooth implants in the anterior maxilla following autologous bone augmentation.

PubMed

Hof, M; Pommer, B; Strbac, G D; Sütö, D; Watzek, G; Zechner, W

2013-08-01

Autologous bone augmentation to rebuild compromised alveolar ridge contour prior to implant placement allows for favorable three-dimensional implant positioning to achieve optimum implant esthetics. The aim of the present study was to evaluate peri-implant soft tissue conditions around single-tooth implants following bone grafts in the esthetic zone of the maxilla. Sixty patients underwent autologous bone augmentation of deficient maxillary sites prior to placement of 85 implants in the esthetic zone. In case of multiple implants per patient, one implant was randomly selected. Objective evaluation of 60 single-tooth implants was performed using the Pink-Esthetic-Score (PES) and Papilla Index (PI) and supplemented by subjective patient evaluation, as well as clinical and radiologic examination. Objective ratings of implant esthetics were satisfactory (median PES: 11, median PI: 2) and significantly correlated with high patient satisfaction (mean VAS score: 80%). Both esthetic indices demonstrated respectable levels of inter- as well as intra-observer agreement. Poor implant esthetics (low PES and PI ratings) were significantly associated with increased anatomic crown height, while no influence of horizontal implant-tooth distance could be found. The present investigation indicates that favorable esthetic results may be achieved in the augmented anterior maxilla. However, bony reconstruction of compromised alveolar ridges does not guarantee optimum implant esthetics. © 2011 John Wiley & Sons A/S.

Multiple retentive means for prosthetic restoration of a large facial defect - a case report.

PubMed

Abdulhadi, Laith Mahmoud

2010-01-01

A 70-year-old man who suffered from extensive extra and intraoral defects was rehabilitated with a prosthesis using multiple retaining means. The treatment was performed in two parts: externally involving the construction of an episthesis supported only by the remaining intact boundaries of the defect and retained by mini-dental implants and spectacle frame with a modified ear hook; and intraorally by an acrylic resin obturator to restore the function of the hemi-sectioned hard and soft palate. The episthesis was securely retained with minimal movement and/or dislodgment of the prosthesis during function. Multiple retentive techniques may be used to fix heavy external prostheses as an alternative to conventional implants or biological adhesives.

Supervised segmentation of microelectrode recording artifacts using power spectral density.

PubMed

Bakstein, Eduard; Schneider, Jakub; Sieger, Tomas; Novak, Daniel; Wild, Jiri; Jech, Robert

2015-08-01

Appropriate detection of clean signal segments in extracellular microelectrode recordings (MER) is vital for maintaining high signal-to-noise ratio in MER studies. Existing alternatives to manual signal inspection are based on unsupervised change-point detection. We present a method of supervised MER artifact classification, based on power spectral density (PSD) and evaluate its performance on a database of 95 labelled MER signals. The proposed method yielded test-set accuracy of 90%, which was close to the accuracy of annotation (94%). The unsupervised methods achieved accuracy of about 77% on both training and testing data.