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

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.

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

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.

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

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

Wireless multichannel biopotential recording using an integrated FM telemetry circuit.

PubMed

Mohseni, Pedram; Najafi, Khalil; Eliades, Steven J; Wang, Xiaoqin

2005-09-01

This paper presents a four-channel telemetric microsystem featuring on-chip alternating current amplification, direct current baseline stabilization, clock generation, time-division multiplexing, and wireless frequency-modulation transmission of microvolt- and millivolt-range input biopotentials in the very high frequency band of 94-98 MHz over a distance of approximately 0.5 m. It consists of a 4.84-mm2 integrated circuit, fabricated using a 1.5-microm double-poly double-metal n-well standard complementary metal-oxide semiconductor process, interfaced with only three off-chip components on a custom-designed printed-circuit board that measures 1.7 x 1.2 x 0.16 cm3, and weighs 1.1 g including two miniature 1.5-V batteries. We characterize the microsystem performance, operating in a truly wireless fashion in single-channel and multichannel operation modes, via extensive benchtop and in vitro tests in saline utilizing two different micromachined neural recording microelectrodes, while dissipating approximately 2.2 mW from a 3-V power supply. Moreover, we demonstrate successful wireless in vivo recording of spontaneous neural activity at 96.2 MHz from the auditory cortex of an awake marmoset monkey at several transmission distances ranging from 10 to 50 cm with signal-to-noise ratios in the range of 8.4-9.5 dB.

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

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.

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.

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.

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.

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.

A Low-Noise, Modular, and Versatile Analog Front-End Intended for Processing In Vitro Neuronal Signals Detected by Microelectrode Arrays

PubMed Central

Regalia, Giulia; Biffi, Emilia; Ferrigno, Giancarlo; Pedrocchi, Alessandra

2015-01-01

The collection of good quality extracellular neuronal spikes from neuronal cultures coupled to Microelectrode Arrays (MEAs) is a binding requirement to gather reliable data. Due to physical constraints, low power requirement, or the need of customizability, commercial recording platforms are not fully adequate for the development of experimental setups integrating MEA technology with other equipment needed to perform experiments under climate controlled conditions, like environmental chambers or cell culture incubators. To address this issue, we developed a custom MEA interfacing system featuring low noise, low power, and the capability to be readily integrated inside an incubator-like environment. Two stages, a preamplifier and a filter amplifier, were designed, implemented on printed circuit boards, and tested. The system is characterized by a low input-referred noise (<1 μV RMS), a high channel separation (>70 dB), and signal-to-noise ratio values of neuronal recordings comparable to those obtained with the benchmark commercial MEA system. In addition, the system was successfully integrated with an environmental MEA chamber, without harming cell cultures during experiments and without being damaged by the high humidity level. The devised system is of practical value in the development of in vitro platforms to study temporally extended neuronal network dynamics by means of MEAs. PMID:25977683

A low-noise, modular, and versatile analog front-end intended for processing in vitro neuronal signals detected by microelectrode arrays.

PubMed

Regalia, Giulia; Biffi, Emilia; Ferrigno, Giancarlo; Pedrocchi, Alessandra

2015-01-01

The collection of good quality extracellular neuronal spikes from neuronal cultures coupled to Microelectrode Arrays (MEAs) is a binding requirement to gather reliable data. Due to physical constraints, low power requirement, or the need of customizability, commercial recording platforms are not fully adequate for the development of experimental setups integrating MEA technology with other equipment needed to perform experiments under climate controlled conditions, like environmental chambers or cell culture incubators. To address this issue, we developed a custom MEA interfacing system featuring low noise, low power, and the capability to be readily integrated inside an incubator-like environment. Two stages, a preamplifier and a filter amplifier, were designed, implemented on printed circuit boards, and tested. The system is characterized by a low input-referred noise (<1 μV RMS), a high channel separation (>70 dB), and signal-to-noise ratio values of neuronal recordings comparable to those obtained with the benchmark commercial MEA system. In addition, the system was successfully integrated with an environmental MEA chamber, without harming cell cultures during experiments and without being damaged by the high humidity level. The devised system is of practical value in the development of in vitro platforms to study temporally extended neuronal network dynamics by means of MEAs.

Enhanced Flexible Tubular Microelectrode with Conducting Polymer for Multi-Functional Implantable Tissue-Machine Interface

NASA Astrophysics Data System (ADS)

Tian, Hong-Chang; Liu, Jing-Quan; Kang, Xiao-Yang; Tang, Long-Jun; Wang, Ming-Hao; Ji, Bo-Wen; Yang, Bin; Wang, Xiao-Lin; Chen, Xiang; Yang, Chun-Sheng

2016-05-01

Implantable biomedical microdevices enable the restoration of body function and improvement of health condition. As the interface between artificial machines and natural tissue, various kinds of microelectrodes with high density and tiny size were developed to undertake precise and complex medical tasks through electrical stimulation and electrophysiological recording. However, if only the electrical interaction existed between electrodes and muscle or nerve tissue without nutrition factor delivery, it would eventually lead to a significant symptom of denervation-induced skeletal muscle atrophy. In this paper, we developed a novel flexible tubular microelectrode integrated with fluidic drug delivery channel for dynamic tissue implant. First, the whole microelectrode was made of biocompatible polymers, which could avoid the drawbacks of the stiff microelectrodes that are easy to be broken and damage tissue. Moreover, the microelectrode sites were circumferentially distributed on the surface of polymer microtube in three dimensions, which would be beneficial to the spatial selectivity. Finally, the in vivo results confirmed that our implantable tubular microelectrodes were suitable for dynamic electrophysiological recording and simultaneous fluidic drug delivery, and the electrode performance was further enhanced by the conducting polymer modification.

Enhanced Flexible Tubular Microelectrode with Conducting Polymer for Multi-Functional Implantable Tissue-Machine Interface.

PubMed

Tian, Hong-Chang; Liu, Jing-Quan; Kang, Xiao-Yang; Tang, Long-Jun; Wang, Ming-Hao; Ji, Bo-Wen; Yang, Bin; Wang, Xiao-Lin; Chen, Xiang; Yang, Chun-Sheng

2016-05-27

Implantable biomedical microdevices enable the restoration of body function and improvement of health condition. As the interface between artificial machines and natural tissue, various kinds of microelectrodes with high density and tiny size were developed to undertake precise and complex medical tasks through electrical stimulation and electrophysiological recording. However, if only the electrical interaction existed between electrodes and muscle or nerve tissue without nutrition factor delivery, it would eventually lead to a significant symptom of denervation-induced skeletal muscle atrophy. In this paper, we developed a novel flexible tubular microelectrode integrated with fluidic drug delivery channel for dynamic tissue implant. First, the whole microelectrode was made of biocompatible polymers, which could avoid the drawbacks of the stiff microelectrodes that are easy to be broken and damage tissue. Moreover, the microelectrode sites were circumferentially distributed on the surface of polymer microtube in three dimensions, which would be beneficial to the spatial selectivity. Finally, the in vivo results confirmed that our implantable tubular microelectrodes were suitable for dynamic electrophysiological recording and simultaneous fluidic drug delivery, and the electrode performance was further enhanced by the conducting polymer modification.

Minimally-Invasive Neural Interface for Distributed Wireless Electrocorticogram Recording Systems

PubMed Central

Chang, Sun-Il

2018-01-01

This paper presents a minimally-invasive neural interface for distributed wireless electrocorticogram (ECoG) recording systems. The proposed interface equips all necessary components for ECoG recording, such as the high performance front-end integrated circuits, a fabricated flexible microelectrode array, and wireless communication inside a miniaturized custom-made platform. The multiple units of the interface systems can be deployed to cover a broad range of the target brain region and transmit signals via a built-in intra-skin communication (ISCOM) module. The core integrated circuit (IC) consists of 16-channel, low-power push-pull double-gated preamplifiers, in-channel successive approximation register analog-to-digital converters (SAR ADC) with a single-clocked bootstrapping switch and a time-delayed control unit, an ISCOM module for wireless data transfer through the skin instead of a power-hungry RF wireless transmitter, and a monolithic voltage/current reference generator to support the aforementioned analog and mixed-signal circuit blocks. The IC was fabricated using 250 nm CMOS processes in an area of 3.2 × 0.9 mm2 and achieved the low-power operation of 2.5 µW per channel. Input-referred noise was measured as 5.62 µVrms for 10 Hz to 10 kHz and ENOB of 7.21 at 31.25 kS/s. The implemented system successfully recorded multi-channel neural activities in vivo from a primate and demonstrated modular expandability using the ISCOM with power consumption of 160 µW. PMID:29342103

Minimally-Invasive Neural Interface for Distributed Wireless Electrocorticogram Recording Systems.

PubMed

Chang, Sun-Il; Park, Sung-Yun; Yoon, Euisik

2018-01-17

This paper presents a minimally-invasive neural interface for distributed wireless electrocorticogram (ECoG) recording systems. The proposed interface equips all necessary components for ECoG recording, such as the high performance front-end integrated circuits, a fabricated flexible microelectrode array, and wireless communication inside a miniaturized custom-made platform. The multiple units of the interface systems can be deployed to cover a broad range of the target brain region and transmit signals via a built-in intra-skin communication (ISCOM) module. The core integrated circuit (IC) consists of 16-channel, low-power push-pull double-gated preamplifiers, in-channel successive approximation register analog-to-digital converters (SAR ADC) with a single-clocked bootstrapping switch and a time-delayed control unit, an ISCOM module for wireless data transfer through the skin instead of a power-hungry RF wireless transmitter, and a monolithic voltage/current reference generator to support the aforementioned analog and mixed-signal circuit blocks. The IC was fabricated using 250 nm CMOS processes in an area of 3.2 × 0.9 mm² and achieved the low-power operation of 2.5 µW per channel. Input-referred noise was measured as 5.62 µV rms for 10 Hz to 10 kHz and ENOB of 7.21 at 31.25 kS/s. The implemented system successfully recorded multi-channel neural activities in vivo from a primate and demonstrated modular expandability using the ISCOM with power consumption of 160 µW.

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.

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.

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

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...

Enhanced Flexible Tubular Microelectrode with Conducting Polymer for Multi-Functional Implantable Tissue-Machine Interface

PubMed Central

Tian, Hong-Chang; Liu, Jing-Quan; Kang, Xiao-Yang; Tang, Long-Jun; Wang, Ming-Hao; Ji, Bo-Wen; Yang, Bin; Wang, Xiao-Lin; Chen, Xiang; Yang, Chun-Sheng

2016-01-01

Implantable biomedical microdevices enable the restoration of body function and improvement of health condition. As the interface between artificial machines and natural tissue, various kinds of microelectrodes with high density and tiny size were developed to undertake precise and complex medical tasks through electrical stimulation and electrophysiological recording. However, if only the electrical interaction existed between electrodes and muscle or nerve tissue without nutrition factor delivery, it would eventually lead to a significant symptom of denervation-induced skeletal muscle atrophy. In this paper, we developed a novel flexible tubular microelectrode integrated with fluidic drug delivery channel for dynamic tissue implant. First, the whole microelectrode was made of biocompatible polymers, which could avoid the drawbacks of the stiff microelectrodes that are easy to be broken and damage tissue. Moreover, the microelectrode sites were circumferentially distributed on the surface of polymer microtube in three dimensions, which would be beneficial to the spatial selectivity. Finally, the in vivo results confirmed that our implantable tubular microelectrodes were suitable for dynamic electrophysiological recording and simultaneous fluidic drug delivery, and the electrode performance was further enhanced by the conducting polymer modification. PMID:27229174

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

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.

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.

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

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.

Intracranial microprobe for evaluating neuro-hemodynamic coupling in unanesthetized human neocortex

PubMed Central

Keller, Corey J.; Cash, Sydney S.; Narayanan, Suresh; Wang, Chunmao; Kuzniecky, Ruben; Carlson, Chad; Devinsky, Orrin; Thesen, Thomas; Doyle, Werner; Sassaroli, Angelo; Boas, David A.; Ulbert, Istvan; Halgren, Eric

2009-01-01

Measurement of the blood-oxygen-level dependent (BOLD) response with fMRI has revolutionized cognitive neuroscience and is increasingly important in clinical care. The BOLD response reflects changes in deoxy-hemoglobin concentration, blood volume, and blood flow. These hemodynamic changes ultimately result from neuronal firing and synaptic activity, but the linkage between these domains is complex, poorly understood, and may differ across species, cortical areas, diseases, and cognitive states. We describe here a technique that can measure neural and hemodynamic changes simultaneously from cortical microdomains in waking humans. We utilize a “laminar optode,” a linear array of microelectrodes for electrophysiological measures paired with a micro-optical device for hemodynamic measurements. Optical measurements include laser Doppler to estimate cerebral blood flow as well as point spectroscopy to estimate oxy- and deoxy-hemoglobin concentrations. The microelectrode array records local field potential gradients (PG) and multi-unit activity (MUA) at 24 locations spanning the cortical depth, permitting estimation of population trans-membrane current flows (Current Source Density, CSD) and population cell firing in each cortical lamina. Comparison of the laminar CSD/MUA profile with the origins and terminations of cortical circuits allows activity in specific neuronal circuits to be inferred and then directly compared to hemodynamics. Access is obtained in epileptic patients during diagnostic evaluation for surgical therapy. Validation tests with relatively well-understood manipulations (EKG, breath-holding, cortical electrical stimulation) demonstrate the expected responses. This device can provide a new and robust means for obtaining detailed, quantitative data for defining neurovascular coupling in awake humans. PMID:19428529

Intracranial microprobe for evaluating neuro-hemodynamic coupling in unanesthetized human neocortex.

PubMed

Keller, Corey J; Cash, Sydney S; Narayanan, Suresh; Wang, Chunmao; Kuzniecky, Ruben; Carlson, Chad; Devinsky, Orrin; Thesen, Thomas; Doyle, Werner; Sassaroli, Angelo; Boas, David A; Ulbert, Istvan; Halgren, Eric

2009-05-15

Measurement of the blood-oxygen-level dependent (BOLD) response with fMRI has revolutionized cognitive neuroscience and is increasingly important in clinical care. The BOLD response reflects changes in deoxy-hemoglobin concentration, blood volume, and blood flow. These hemodynamic changes ultimately result from neuronal firing and synaptic activity, but the linkage between these domains is complex, poorly understood, and may differ across species, cortical areas, diseases, and cognitive states. We describe here a technique that can measure neural and hemodynamic changes simultaneously from cortical microdomains in waking humans. We utilize a "laminar optode," a linear array of microelectrodes for electrophysiological measures paired with a micro-optical device for hemodynamic measurements. Optical measurements include laser Doppler to estimate cerebral blood flow as well as point spectroscopy to estimate oxy- and deoxy-hemoglobin concentrations. The microelectrode array records local field potential gradients (PG) and multi-unit activity (MUA) at 24 locations spanning the cortical depth, permitting estimation of population trans-membrane current flows (Current Source Density, CSD) and population cell firing in each cortical lamina. Comparison of the laminar CSD/MUA profile with the origins and terminations of cortical circuits allows activity in specific neuronal circuits to be inferred and then directly compared to hemodynamics. Access is obtained in epileptic patients during diagnostic evaluation for surgical therapy. Validation tests with relatively well-understood manipulations (EKG, breath-holding, cortical electrical stimulation) demonstrate the expected responses. This device can provide a new and robust means for obtaining detailed, quantitative data for defining neurovascular coupling in awake humans.

Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces

PubMed Central

Kozai, Takashi D. Yoshida; Langhals, Nicholas B.; Patel, Paras R.; Deng, Xiaopei; Zhang, Huanan; Smith, Karen L.; Lahann, Joerg; Kotov, Nicholas A.; Kipke, Daryl R.

2012-01-01

Implantable neural microelectrodes that can record extracellular biopotentials from small, targeted groups of neurons are critical for neuroscience research and emerging clinical applications including brain-controlled prosthetic devices. The crucial material-dependent problem is developing microelectrodes that record neural activity from the same neurons for years with high fidelity and reliability. Here, we report the development of an integrated composite electrode consisting of a carbon-fibre core, a poly(p-xylylene)-based thin-film coating that acts as a dielectric barrier and that is functionalized to control intrinsic biological processes, and a poly(thiophene)-based recording pad. The resulting implants are an order of magnitude smaller than traditional recording electrodes, and more mechanically compliant with brain tissue. They were found to elicit much reduced chronic reactive tissue responses and enabled single-neuron recording in acute and early chronic experiments in rats. This technology, taking advantage of new composites, makes possible highly selective and stealthy neural interface devices towards realizing long-lasting implants. PMID:23142839

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...

Assessment of gliosis around moveable implants in the brain

PubMed Central

Stice, Paula

2010-01-01

Repositioning microelectrodes post-implantation is emerging as a promising approach to achieve long-term reliability in single neuronal recordings. The main goal of this study was to (a) assess glial reaction in response to movement of microelectrodes in the brain post-implantation and (b) determine an optimal window of time post-implantation when movement of microelectrodes within the brain would result in minimal glial reaction. Eleven Sprague-Dawley rats were implanted with two microelectrodes each that could be moved in vivo post-implantation. Three cohorts were investigated: (1) microelectrode moved at day 2 (n = 4 animals), (2) microelectrode moved at day 14 (n = 5 animals) and (3) microelectrode moved at day 28 (n = 2 animals). Histological evaluation was performed in cohorts 1–3 at four-week post-movement (30 days, 42 days and 56 days post-implantation, respectively). In addition, five control animals were implanted with microelectrodes that were not moved. Control animals were implanted for (1) 30 days (n = 1), (2) 42 days (n = 2) and (3) 56 days (n = 2) prior to histological evaluation. Quantitative assessment of glial fibrillary acidic protein (GFAP) around the tip of the microelectrodes demonstrated that GFAP levels were similar around microelectrodes moved at day 2 when compared to the 30-day controls. However, GFAP expression levels around microelectrode tips that moved at day 14 and day 28 were significantly less than those around control microelectrodes implanted for 42 and 56 days, respectively. Therefore, we conclude that moving microelectrodes after implantation is a viable strategy that does not result in any additional damage to brain tissue. Further, moving the microelectrode downwards after 14 days of implantation may actually reduce the levels of GFAP expression around the tips of the microelectrodes in the long term. PMID:19556680

Twenty-four-micrometer-pitch microelectrode array with 6912-channel readout at 12 kHz via highly scalable implementation for high-spatial-resolution mapping of action potentials.

PubMed

Ogi, Jun; Kato, Yuri; Matoba, Yoshihisa; Yamane, Chigusa; Nagahata, Kazunori; Nakashima, Yusaku; Kishimoto, Takuya; Hashimoto, Shigeki; Maari, Koichi; Oike, Yusuke; Ezaki, Takayuki

2017-12-19

A 24-μm-pitch microelectrode array (MEA) with 6912 readout channels at 12 kHz and 23.2-μV rms random noise is presented. The aim is to reduce noise in a "highly scalable" MEA with a complementary metal-oxide-semiconductor integration circuit (CMOS-MEA), in which a large number of readout channels and a high electrode density can be expected. Despite the small dimension and the simplicity of the in-pixel circuit for the high electrode-density and the relatively large number of readout channels of the prototype CMOS-MEA chip developed in this work, the noise within the chip is successfully reduced to less than half that reported in a previous work, for a device with similar in-pixel circuit simplicity and a large number of readout channels. Further, the action potential was clearly observed on cardiomyocytes using the CMOS-MEA. These results indicate the high-scalability of the CMOS-MEA. The highly scalable CMOS-MEA provides high-spatial-resolution mapping of cell action potentials, and the mapping can aid understanding of complex activities in cells, including neuron network activities.

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.

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.

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

Pin-deposition of conductive inks for microelectrodes and contact via filling

DOEpatents

Davidson, J. Courtney; Krulevitch, Peter A.; Maghribi, Mariam N.; Hamilton, Julie K.; Benett, William J.; Tovar, Armando R.

2006-05-02

A method of metalization of an integrated microsystem. The method comprises providing a substrate and applying a conductive material to the substrate by taking up small aliquots of conductive material and releasing the conductive material onto the substrate to produce a circuit component.

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

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.

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...

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.

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...

Acute Hippocampal Slice Preparation and Hippocampal Slice Cultures

PubMed Central

Lein, Pamela J.; Barnhart, Christopher D.; Pessah, Isaac N.

2012-01-01

A major advantage of hippocampal slice preparations is that the cytoarchitecture and synaptic circuits of the hippocampus are largely retained. In neurotoxicology research, organotypic hippocampal slices have mostly been used as acute ex vivo preparations for investigating the effects of neurotoxic chemicals on synaptic function. More recently, hippocampal slice cultures, which can be maintained for several weeks to several months in vitro, have been employed to study how neurotoxic chemicals influence the structural and functional plasticity in hippocampal neurons. This chapter provides protocols for preparing hippocampal slices to be used acutely for electrophysiological measurements using glass microelectrodes or microelectrode arrays or to be cultured for morphometric assessments of individual neurons labeled using biolistics. PMID:21815062

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.

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.

An externally head-mounted wireless neural recording device for laboratory animal research and possible human clinical use.

PubMed

Yin, Ming; Li, Hao; Bull, Christopher; Borton, David A; Aceros, Juan; Larson, Lawrence; Nurmikko, Arto V

2013-01-01

In this paper we present a new type of head-mounted wireless neural recording device in a highly compact package, dedicated for untethered laboratory animal research and designed for future mobile human clinical use. The device, which takes its input from an array of intracortical microelectrode arrays (MEA) has ninety-seven broadband parallel neural recording channels and was integrated on to two custom designed printed circuit boards. These house several low power, custom integrated circuits, including a preamplifier ASIC, a controller ASIC, plus two SAR ADCs, a 3-axis accelerometer, a 48MHz clock source, and a Manchester encoder. Another ultralow power RF chip supports an OOK transmitter with the center frequency tunable from 3GHz to 4GHz, mounted on a separate low loss dielectric board together with a 3V LDO, with output fed to a UWB chip antenna. The IC boards were interconnected and packaged in a polyether ether ketone (PEEK) enclosure which is compatible with both animal and human use (e.g. sterilizable). The entire system consumes 17mA from a 1.2Ahr 3.6V Li-SOCl2 1/2AA battery, which operates the device for more than 2 days. The overall system includes a custom RF receiver electronics which are designed to directly interface with any number of commercial (or custom) neural signal processors for multi-channel broadband neural recording. Bench-top measurements and in vivo testing of the device in rhesus macaques are presented to demonstrate the performance of the wireless neural interface.

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.

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.

Single-cell recording and stimulation with a 16k micro-nail electrode array integrated on a 0.18 μm CMOS chip.

PubMed

Huys, Roeland; Braeken, Dries; Jans, Danny; Stassen, Andim; Collaert, Nadine; Wouters, Jan; Loo, Josine; Severi, Simone; Vleugels, Frank; Callewaert, Geert; Verstreken, Kris; Bartic, Carmen; Eberle, Wolfgang

2012-04-07

To cope with the growing needs in research towards the understanding of cellular function and network dynamics, advanced micro-electrode arrays (MEAs) based on integrated complementary metal oxide semiconductor (CMOS) circuits have been increasingly reported. Although such arrays contain a large number of sensors for recording and/or stimulation, the size of the electrodes on these chips are often larger than a typical mammalian cell. Therefore, true single-cell recording and stimulation remains challenging. Single-cell resolution can be obtained by decreasing the size of the electrodes, which inherently increases the characteristic impedance and noise. Here, we present an array of 16,384 active sensors monolithically integrated on chip, realized in 0.18 μm CMOS technology for recording and stimulation of individual cells. Successful recording of electrical activity of cardiac cells with the chip, validated with intracellular whole-cell patch clamp recordings are presented, illustrating single-cell readout capability. Further, by applying a single-electrode stimulation protocol, we could pace individual cardiac cells, demonstrating single-cell addressability. This novel electrode array could help pave the way towards solving complex interactions of mammalian cellular networks. This journal is © The Royal Society of Chemistry 2012

Portable wireless electrocorticography system with a flexible microelectrodes array for epilepsy treatment.

PubMed

Xie, Kejun; Zhang, Shaomin; Dong, Shurong; Li, Shijian; Yu, Chaonan; Xu, Kedi; Chen, Wanke; Guo, Wei; Luo, Jikui; Wu, Zhaohui

2017-08-10

In this paper, we present a portable wireless electrocorticography (ECoG) system. It uses a high resolution 32-channel flexible ECoG electrodes array to collect electrical signals of brain activities and to stimulate the lesions. Electronic circuits are designed for signal acquisition, processing and transmission using Bluetooth Low Energy 4 (LTE4) for wireless communication with cell phone. In-vivo experiments on a rat show that the flexible ECoG system can accurately record electrical signals of brain activities and transmit them to cell phone with a maximal sampling rate of 30 ksampling/s per channel. It demonstrates that the epilepsy lesions can be detected, located and treated through the ECoG system. The wireless ECoG system has low energy consumption and high brain spatial resolution, thus has great prospects for future application.

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

A feasibility study of multi-site,intracellular recordings from mammalian neurons by extracellular gold mushroom-shaped microelectrodes.

PubMed

Ojovan, Silviya M; Rabieh, Noha; Shmoel, Nava; Erez, Hadas; Maydan, Eilon; Cohen, Ariel; Spira, Micha E

2015-09-14

The development of multi-electrode array platforms for large scale recording of neurons is at the forefront of neuro-engineering research efforts. Recently we demonstrated, at the proof-of-concept level, a breakthrough neuron-microelectrode interface in which cultured Aplysia neurons tightly engulf gold mushroom-shaped microelectrodes (gMμEs). While maintaining their extracellular position, the gMμEs record synaptic- and action-potentials with characteristic features of intracellular recordings. Here we examined the feasibility of using gMμEs for intracellular recordings from mammalian neurons. To that end we experimentally examined the innate size limits of cultured rat hippocampal neurons to engulf gMμEs and measured the width of the "extracellular" cleft formed between the neurons and the gold surface. Using the experimental results we next analyzed the expected range of gMμEs-neuron electrical coupling coefficients. We estimated that sufficient electrical coupling levels to record attenuated synaptic- and action-potentials can be reached using the gMμE-neuron configuration. The definition of the engulfment limits of the gMμEs caps diameter at ≤2-2.5 μm and the estimated electrical coupling coefficients from the simulations pave the way for rational development and application of the gMμE based concept for in-cell recordings from mammalian neurons.

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.

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.

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.

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.

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.

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.

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.

Stop! border ahead: Automatic detection of subthalamic exit during deep brain stimulation surgery.

PubMed

Valsky, Dan; Marmor-Levin, Odeya; Deffains, Marc; Eitan, Renana; Blackwell, Kim T; Bergman, Hagai; Israel, Zvi

2017-01-01

Microelectrode recordings along preplanned trajectories are often used for accurate definition of the subthalamic nucleus (STN) borders during deep brain stimulation (DBS) surgery for Parkinson's disease. Usually, the demarcation of the STN borders is performed manually by a neurophysiologist. The exact detection of the borders is difficult, especially detecting the transition between the STN and the substantia nigra pars reticulata. Consequently, demarcation may be inaccurate, leading to suboptimal location of the DBS lead and inadequate clinical outcomes. We present machine-learning classification procedures that use microelectrode recording power spectra and allow for real-time, high-accuracy discrimination between the STN and substantia nigra pars reticulata. A support vector machine procedure was tested on microelectrode recordings from 58 trajectories that included both STN and substantia nigra pars reticulata that achieved a 97.6% consistency with human expert classification (evaluated by 10-fold cross-validation). We used the same data set as a training set to find the optimal parameters for a hidden Markov model using both microelectrode recording features and trajectory history to enable real-time classification of the ventral STN border (STN exit). Seventy-three additional trajectories were used to test the reliability of the learned statistical model in identifying the exit from the STN. The hidden Markov model procedure identified the STN exit with an error of 0.04 ± 0.18 mm and detection reliability (error < 1 mm) of 94%. The results indicate that robust, accurate, and automatic real-time electrophysiological detection of the ventral STN border is feasible. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Three-dimensional micro-electrode array for recording dissociated neuronal cultures.

PubMed

Musick, Katherine; Khatami, David; Wheeler, Bruce C

2009-07-21

This work demonstrates the design, fabrication, packaging, characterization, and functionality of an electrically and fluidically active three-dimensional micro-electrode array (3D MEA) for use with neuronal cell cultures. The successful function of the device implies that this basic concept-construction of a 3D array with a layered approach-can be utilized as the basis for a new family of neural electrode arrays. The 3D MEA prototype consists of a stack of individually patterned thin films that form a cell chamber conducive to maintaining and recording the electrical activity of a long-term three-dimensional network of rat cortical neurons. Silicon electrode layers contain a polymer grid for neural branching, growth, and network formation. Along the walls of these electrode layers lie exposed gold electrodes which permit recording and stimulation of the neuronal electrical activity. Silicone elastomer micro-fluidic layers provide a means for loading dissociated neurons into the structure and serve as the artificial vasculature for nutrient supply and aeration. The fluidic layers also serve as insulation for the micro-electrodes. Cells have been shown to survive in the 3D MEA for up to 28 days, with spontaneous and evoked electrical recordings performed in that time. The micro-fluidic capability was demonstrated by flowing in the drug tetrotodoxin to influence the activity of the culture.

A Multi-Channel, Flex-Rigid ECoG Microelectrode Array for Visual Cortical Interfacing

PubMed Central

Tolstosheeva, Elena; Gordillo-González, Víctor; Biefeld, Volker; Kempen, Ludger; Mandon, Sunita; Kreiter, Andreas K.; Lang, Walter

2015-01-01

High-density electrocortical (ECoG) microelectrode arrays are promising signal-acquisition platforms for brain-computer interfaces envisioned, e.g., as high-performance communication solutions for paralyzed persons. We propose a multi-channel microelectrode array capable of recording ECoG field potentials with high spatial resolution. The proposed array is of a 150 mm2 total recording area; it has 124 circular electrodes (100, 300 and 500 μm in diameter) situated on the edges of concentric hexagons (min. 0.8 mm interdistance) and a skull-facing reference electrode (2.5 mm2 surface area). The array is processed as a free-standing device to enable monolithic integration of a rigid interposer, designed for soldering of fine-pitch SMD-connectors on a minimal assembly area. Electrochemical characterization revealed distinct impedance spectral bands for the 100, 300 and 500 μm-type electrodes, and for the array's own reference. Epidural recordings from the primary visual cortex (V1) of an awake Rhesus macaque showed natural electrophysiological signals and clear responses to standard visual stimulation. The ECoG electrodes of larger surface area recorded signals with greater spectral power in the gamma band, while the skull-facing reference electrode provided higher average gamma power spectral density (γPSD) than the common average referencing technique. PMID:25569757

Close-Packed Silicon Microelectrodes for Scalable Spatially Oversampled Neural Recording

PubMed Central

Scholvin, Jörg; Kinney, Justin P.; Bernstein, Jacob G.; Moore-Kochlacs, Caroline; Kopell, Nancy; Fonstad, Clifton G.; Boyden, Edward S.

2015-01-01

Objective Neural recording electrodes are important tools for understanding neural codes and brain dynamics. Neural electrodes that are close-packed, such as in tetrodes, enable spatial oversampling of neural activity, which facilitates data analysis. Here we present the design and implementation of close-packed silicon microelectrodes, to enable spatially oversampled recording of neural activity in a scalable fashion. Methods Our probes are fabricated in a hybrid lithography process, resulting in a dense array of recording sites connected to submicron dimension wiring. Results We demonstrate an implementation of a probe comprising 1000 electrode pads, each 9 × 9 μm, at a pitch of 11 μm. We introduce design automation and packaging methods that allow us to readily create a large variety of different designs. Significance Finally, we perform neural recordings with such probes in the live mammalian brain that illustrate the spatial oversampling potential of closely packed electrode sites. PMID:26699649

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.

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.

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

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

Clinical applications of penetrating neural interfaces and Utah Electrode Array technologies

NASA Astrophysics Data System (ADS)

Normann, Richard A.; Fernandez, Eduardo

2016-12-01

This paper briefly describes some of the recent progress in the development of penetrating microelectrode arrays and highlights the use of two of these devices, Utah electrode arrays and Utah slanted electrode arrays, in two therapeutic interventions: recording volitional skeletal motor commands from the central nervous system, and recording motor commands and evoking somatosensory percepts in the peripheral nervous system (PNS). The paper also briefly explores other potential sites for microelectrode array interventions that could be profitably pursued and that could have important consequences in enhancing the quality of life of patients that has been compromised by disorders of the central and PNSs.

Design and fabrication of a flexible substrate microelectrode array for brain machine interfaces.

PubMed

Patrick, Erin; Ordonez, Matthew; Alba, Nicolas; Sanchez, Justin C; Nishida, Toshikazu

2006-01-01

We report a neural microelectrode array design that leverages the recording properties of conventional microwire electrode arrays with the additional features of precise control of the electrode geometries. Using microfabrication techniques, a neural probe array is fabricated that possesses a flexible polyimide-based cable. The performance of the design was tested with electrochemical impedance spectroscopy and in vivo studies. The gold-plated electrode site has an impedance value of 0.9 M Omega at 1 kHz. Acute neural recording provided high neuronal yields, peak-to-peak amplitudes (as high as 100 microV), and signal-to-noise ratios (27 dB).

A novel bio-mimicking, planar nano-edge microelectrode enables enhanced long-term neural recording

NASA Astrophysics Data System (ADS)

Wijdenes, Pierre; Ali, Hasan; Armstrong, Ryden; Zaidi, Wali; Dalton, Colin; Syed, Naweed I.

2016-10-01

Our inability to accurately monitor individual neurons and their synaptic activity precludes fundamental understanding of brain function under normal and various pathological conditions. However, recent breakthroughs in micro- and nano-scale fabrication processes have advanced the development of neuro-electronic hybrid technology. Among such devices are three-dimensional and planar electrodes, offering the advantages of either high fidelity or longer-term recordings respectively. Here, we present the next generation of planar microelectrode arrays with “nano-edges” that enable long-term (≥1 month) and high fidelity recordings at a resolution 15 times higher than traditional planar electrodes. This novel technology enables better understanding of brain function and offers a tremendous opportunity towards the development of future bionic hybrids and drug discovery devices.

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.

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

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.

Electrochemical noise and impedance of Au electrode/electrolyte interfaces enabling extracellular detection of glioma cell populations

NASA Astrophysics Data System (ADS)

Rocha, Paulo R. F.; Schlett, Paul; Kintzel, Ulrike; Mailänder, Volker; Vandamme, Lode K. J.; Zeck, Gunther; Gomes, Henrique L.; Biscarini, Fabio; de Leeuw, Dago M.

2016-10-01

Microelectrode arrays (MEA) record extracellular local field potentials of cells adhered to the electrodes. A disadvantage is the limited signal-to-noise ratio. The state-of-the-art background noise level is about 10 μVpp. Furthermore, in MEAs low frequency events are filtered out. Here, we quantitatively analyze Au electrode/electrolyte interfaces with impedance spectroscopy and noise measurements. The equivalent circuit is the charge transfer resistance in parallel with a constant phase element that describes the double layer capacitance, in series with a spreading resistance. This equivalent circuit leads to a Maxwell-Wagner relaxation frequency, the value of which is determined as a function of electrode area and molarity of an aqueous KCl electrolyte solution. The electrochemical voltage and current noise is measured as a function of electrode area and frequency and follow unambiguously from the measured impedance. By using large area electrodes the noise floor can be as low as 0.3 μVpp. The resulting high sensitivity is demonstrated by the extracellular detection of C6 glioma cell populations. Their minute electrical activity can be clearly detected at a frequency below about 10 Hz, which shows that the methodology can be used to monitor slow cooperative biological signals in cell populations.

The impact of multichannel microelectrode recording (MER) in deep brain stimulation of the basal ganglia.

PubMed

Kinfe, Thomas M; Vesper, Jan

2013-01-01

Deep brain stimulation (DBS) of the basal ganglia (Ncl. subthalamicus, Ncl. ventralis intermedius thalami, globus pallidus internus) has become an evidence-based and well-established treatment option in otherwise refractory movement disorders. The Ncl. subthalamicus (STN) is the target of choice in Parkinson's disease.However, a considerable discussion is currently ongoing with regard to the necessity for micro-electrode recording (MER) in DBS surgery.The present review provides an overview on deep brain stimulation and (MER) of the STN in patients with Parkinson's disease. Detailed description is given concerning the multichannel MER systems nowadays available for DBS of the basal ganglia, especially of the STN, as a useful tool for target refinement. Furthermore, an overview is given of the historical aspects, spatial mapping of the STN by MER, and its impact for accuracy and precision in current functional stereotactic neurosurgery.The pros concerning target refinement by MER means on the one hand, and cons including increased bleeding risk, increased operation time, local or general anesthesia, and single versus multichannel microelectrode recording are discussed in detail. Finally, the authors favor the use of MER with intraoperative testing combined with imaging to achieve a more precise electrode placement, aiming to ameliorate clinical outcome in therapy-resistant movement disorders.

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

DTIC Science & Technology

2017-10-01

potentials or multi-action potential activity from residual peripheral nerve while patient intends movements of amputated hand/arm Subtask 3.1: Mapping of...neural activity (Months 4 – 36) • Patients will be asked to intend a number of individual finger and multiple finger flexion, extension, adduction...intended movements. We will map the different intended movements onto the neural activity recorded on the electrodes of the micro-electrode array

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

DTIC Science & Technology

2016-10-01

isolated action potentials or multi-action potential activity from residual peripheral nerve while patient intends movements of amputated hand/arm...Subtask 3.1: Mapping of neural activity (Months 4 – 36) • Patients will be asked to intend a number of individual finger and multiple finger flexion...during these intended movements. We will map the different intended movements onto the neural activity recorded on the electrodes of the micro-electrode

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.

Cytotopographical specialization of enzymatically isolated rabbit retinal Müller (glial) cells: K+ conductivity of the cell membrane.

PubMed

Reichenbach, A; Eberhardt, W

1988-01-01

Müller (radial glial) cells were isolated from rabbit retinae by means of papaine and mechanical dissociation. Regional membrane properties of these cells were studied by intracellular microelectrode recordings of potential responses to local application of high K+ solutions. When different parts of the cell membrane were exposed to high K+, the amplitude of the depolarizing responses varied greatly, indicating a strong regional specialization of the membrane properties. Using morphometrical data of isolated rabbit Müller cells, and a simple circuit model, we calculated the endfoot membrane to constitute more than 80% of the total K+ conductance of the cell; the specific resistivity of the endfoot membrane was about 400 omega cm2, i.e., more than 40 times less than that of the membrane of the vitread process, which is immediately adjacent. This kind of regional membrane specialization seems to be optimized in respect to the Müller cells' ability to carry spatial buffering K+ currents.

Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

NASA Astrophysics Data System (ADS)

Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J.

2016-08-01

A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs.

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

Voluntary control of intracortical oscillations for reconfiguration of network activity

PubMed Central

Corlier, Juliana; Valderrama, Mario; Navarrete, Miguel; Lehongre, Katia; Hasboun, Dominique; Adam, Claude; Belaid, Hayat; Clémenceau, Stéphane; Baulac, Michel; Charpier, Stéphane; Navarro, Vincent; Le Van Quyen, Michel

2016-01-01

Voluntary control of oscillatory activity represents a key target in the self-regulation of brain function. Using a real-time closed-loop paradigm and simultaneous macro- and micro-electrode recordings, we studied the effects of self-induced intracortical oscillatory activity (4–8 Hz) in seven neurosurgical patients. Subjects learned to robustly and specifically induce oscillations in the target frequency, confirmed by increased oscillatory event density. We have found that the session-to-session variability in performance was explained by the functional long-range decoupling of the target area suggesting a training-induced network reorganization. Downstream effects on more local activities included progressive cross-frequency-coupling with gamma oscillations (30–120 Hz), and the dynamic modulation of neuronal firing rates and spike timing, indicating an improved temporal coordination of local circuits. These findings suggest that effects of voluntary control of intracortical oscillations can be exploited to specifically target plasticity processes to reconfigure network activity, with a particular relevance for memory function or skill acquisition. PMID:27808225

Electrical properties of a light-addressable microelectrode chip with high electrode density for extracellular stimulation and recording of excitable cells.

PubMed

Bucher, V; Brunner, B; Leibrock, C; Schubert, M; Nisch, W

2001-05-01

A light-addressable microelectrode chip with 3600 TiN electrodes was fabricated. Amorphous silicon (a-Si:H) serves as a photo conductor. The electrodes on the chip are addressed by a laser spot and electrical properties of the system are determined. DC measurements show a dark to bright dynamic of 10(6)-10(7). The AC impedance dynamic @ 1 kHz/100 mV and thus the signal-to-noise-ratio is determined to 60. This value is quite sufficient for electrophysiological measurements. For the first time, recordings from cardiac myocytes are reported using the principle of light-addressing. Measurements were done with a standard laser scan microscope (Zeiss LSM 410).

Integrated microelectrode array and microfluidics for temperature clamp of sensory neurons in culture.

PubMed

Pearce, Thomas M; Wilson, J Adam; Oakes, S George; Chiu, Shing-Yan; Williams, Justin C

2005-01-01

A device for cell culture is presented that combines MEMS technology and liquid-phase photolithography to create a microfluidic chip that influences and records electrical cellular activity. A photopolymer channel network is formed on top of a multichannel microelectrode array. Preliminary results indicated successful local thermal control within microfluidic channels and control of lamina position over the electrode array. To demonstrate the biological application of such a device, adult dissociated dorsal root ganglion neurons with a subpopulation of thermally-sensitive cells are attached onto the electrode array. Using laminar flow, dynamic control of local temperature of the neural cells was achieved while maintaining a constant chemical culture medium. Recording the expected altered cellular activity confirms the success of the integrated device.

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.

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.

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.

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.

Creation of defined single cell resolution neuronal circuits on microelectrode arrays

NASA Astrophysics Data System (ADS)

Pirlo, Russell Kirk

2009-12-01

The way cell-cell organization of neuronal networks influences activity and facilitates function is not well understood. Microelectrode arrays (MEAs) and advancing cell patterning technologies have enabled access to and control of in vitro neuronal networks spawning much new research in neuroscience and neuroengineering. We propose that small, simple networks of neurons with defined circuitry may serve as valuable research models where every connection can be analyzed, controlled and manipulated. Towards the goal of creating such neuronal networks we have applied microfabricated elastomeric membranes, surface modification and our unique laser cell patterning system to create defined neuronal circuits with single-cell precision on MEAs. Definition of synaptic connectivity was imposed by the 3D physical constraints of polydimethylsiloxane elastomeric membranes. The membranes had 20mum clear-through holes and 2-3mum deep channels which when applied to the surface of the MEA formed microwells to confine neurons to electrodes connected via shallow tunnels to direct neurite outgrowth. Tapering and turning of channels was used to influence neurite polarity. Biocompatibility of the membranes was increased by vacuum baking, oligomer extraction, and autoclaving. Membranes were bound to the MEA by oxygen plasma treatment and heated pressure. The MEA/membrane surface was treated with oxygen plasma, poly-D-lysine and laminin to improve neuron attachment, survival and neurite outgrowth. Prior to cell patterning the outer edge of culture area was seeded with 5x10 5 cells per cm and incubated for 2 days. Single embryonic day 7 chick forebrain neurons were then patterned into the microwells and onto the electrodes using our laser cell patterning system. Patterned neurons successfully attached to and were confined to the electrodes. Neurites extended through the interconnecting channels and connected with adjacent neurons. These results demonstrate that neuronal circuits can be created with clearly defined circuitry and a one-to-one neuron-electrode ratio. The techniques and processes described here may be used in future research to create defined neuronal circuits to model in vivo circuits and study neuronal network processing.

Encapsulating Elastically Stretchable Neural Interfaces: Yield, Resolution, and Recording/Stimulation of Neural Activity

PubMed Central

Morrison, Barclay; Goletiani, Cezar; Yu, Zhe; Wagner, Sigurd

2013-01-01

A high resolution elastically stretchable microelectrode array (SMEA) to interface with neural tissue is described. The SMEA consists of an elastomeric substrate, such as poly(dimethylsiloxane) (PDMS), elastically stretchable gold conductors, and an electrically insulating encapsulating layer in which contact holes are opened. We demonstrate the feasibility of producing contact holes with 40 µm × 40 µm openings, show why the adhesion of the encapsulation layer to the underlying silicone substrate is weakened during contact hole fabrication, and provide remedies. These improvements result in greatly increased fabrication yield and reproducibility. An SMEA with 28 microelectrodes was fabricated. The contact holes (100 µm × 100 µm) in the encapsulation layer are only ~10% the size of the previous generation, allowing a larger number of microelectrodes per unit area, thus affording the capability to interface with a smaller neural population per electrode. This new SMEA is used to record spontaneous and evoked activity in organotypic hippocampal tissue slices at 0% strain before stretching, at 5 % and 10 % equibiaxial strain, and again at 0% strain after relaxation. The noise of the recordings increases with increasing strain. The frequency of spontaneous neural activity also increases when the SMEA is stretched. Upon relaxation, the noise returns to pre-stretch levels, while the frequency of neural activity remains elevated. Stimulus-response curves at each strain level are measured. The SMEA shows excellent biocompatibility for at least two weeks. PMID:24093006

Simultaneous detection of pH changes and histamine release from oxyntic glands in isolated stomach.

PubMed

Bitziou, Eleni; O'Hare, Danny; Patel, Bhavik Anil

2008-11-15

Real-time simultaneous detection of changes in pH and levels of histamine over the oxyntic glands of guinea pig stomach have been investigated. An iridium oxide pH microelectrode was used in a potentiometric mode to record the pH decrease associated with acid secretion when the sensor approached the isolated tissue. A boron-doped diamond (BDD) microelectrode was used in an amperometric mode to detect histamine when the electrode was placed over the tissue. Both sensors provided stable and reproducible responses that were qualitatively consistent with the signaling mechanism for acid secretion at the stomach. Simultaneous measurements in the presence of pharmacological treatments produced significant variations in the signals obtained by both sensors. As the H2 receptor antagonist cimetidine was perfused to the tissue, histamine levels increased that produced an increase in the signal of the BDD electrode whereas the pH sensor recorded a decrease in acid secretion as expected. Addition of acetylcholine (ACh) stimulated additional acid secretion detected with the pH microelectrode whereas the BDD sensor recorded the histamine levels decreasing significantly. This result shows that the primary influence of ACh is directly on the parietal cell receptors rather then the ECL cell receptors of the oxyntic glands. These results highlight the power of this simultaneous detection technique in the monitoring and diagnosis of physiological significant signaling mechanisms and pathways.

In Vivo Validation of Custom-Designed Silicon-Based Microelectrode Arrays for Long-Term Neural Recording and Stimulation

PubMed Central

Manoonkitiwongsa, Panya S.; Wang, Cindy X.; McCreery, Douglas B.

2012-01-01

We developed and validated silicon-based neural probes for neural stimulating and recording in long-term implantation in the brain. The probes combine the deep reactive ion etching process and mechanical shaping of their tip region, yielding a mechanically sturdy shank with a sharpened tip to reduce insertion force into the brain and spinal cord, particularly, with multiple shanks in the same array. The arrays’ insertion forces have been quantified in vitro. Five consecutive chronically-implanted devices were fully functional from 3 to 18 months. The microelectrode sites were electroplated with iridium oxide, and the charge injection capacity measurements were performed both in vitro and after implantation in the adult feline brain. The functionality of the chronic array was validated by stimulating in the cochlear nucleus and recording the evoked neuronal activity in the central nucleus of the inferior colliculus. The arrays’ recording quality has also been quantified in vivo with neuronal spike activity recorded up to 566 days after implantation. Histopathology evaluation of neurons and astrocytes using immunohistochemical stains indicated minimal alterations of tissue architecture after chronic implantation. PMID:22020666

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

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.

Carbon fiber on polyimide ultra-microelectrodes

NASA Astrophysics Data System (ADS)

Gillis, Winthrop F.; Lissandrello, Charles A.; Shen, Jun; Pearre, Ben W.; Mertiri, Alket; Deku, Felix; Cogan, Stuart; Holinski, Bradley J.; Chew, Daniel J.; White, Alice E.; Otchy, Timothy M.; Gardner, Timothy J.

2018-02-01

Objective. Most preparations for making neural recordings degrade over time and eventually fail due to insertion trauma and reactive tissue response. The magnitudes of these responses are thought to be related to the electrode size (specifically, the cross-sectional area), the relative stiffness of the electrode, and the degree of tissue tolerance for the material. Flexible carbon fiber ultra-microelectrodes have a much smaller cross-section than traditional electrodes and low tissue reactivity, and thus may enable improved longevity of neural recordings in the central and peripheral nervous systems. Only two carbon fiber array designs have been described previously, each with limited channel densities due to limitations of the fabrication processes or interconnect strategies. Here, we describe a method for assembling carbon fiber electrodes on a flexible polyimide substrate that is expected to facilitate the construction of high-density recording and stimulating arrays. Approach. Individual carbon fibers were aligned using an alignment tool that was 3D-printed with sub-micron resolution using direct laser writing. Indium deposition on the carbon fibers, followed by low-temperature microsoldering, provided a robust and reliable method of electrical connection to the polyimide interconnect. Main results. Spontaneous multiunit activity and stimulation-evoked compound responses with SNR  >10 and  >120, respectively, were recorded from a small (125 µm) peripheral nerve. We also improved the typically poor charge injection capacity of small diameter carbon fibers by electrodepositing 100 nm-thick iridium oxide films, making the carbon fiber arrays usable for electrical stimulation as well as recording. Significance. Our innovations in fabrication technique pave the way for further miniaturization of carbon fiber ultra-microelectrode arrays. We believe these advances to be key steps to enable a shift from labor intensive, manual assembly to a more automated manufacturing process.

Carbon fiber on polyimide ultra-microelectrodes.

PubMed

Gillis, Winthrop F; Lissandrello, Charles A; Shen, Jun; Pearre, Ben W; Mertiri, Alket; Deku, Felix; Cogan, Stuart; Holinski, Bradley J; Chew, Daniel J; White, Alice E; Otchy, Timothy M; Gardner, Timothy J

2018-02-01

Most preparations for making neural recordings degrade over time and eventually fail due to insertion trauma and reactive tissue response. The magnitudes of these responses are thought to be related to the electrode size (specifically, the cross-sectional area), the relative stiffness of the electrode, and the degree of tissue tolerance for the material. Flexible carbon fiber ultra-microelectrodes have a much smaller cross-section than traditional electrodes and low tissue reactivity, and thus may enable improved longevity of neural recordings in the central and peripheral nervous systems. Only two carbon fiber array designs have been described previously, each with limited channel densities due to limitations of the fabrication processes or interconnect strategies. Here, we describe a method for assembling carbon fiber electrodes on a flexible polyimide substrate that is expected to facilitate the construction of high-density recording and stimulating arrays. Individual carbon fibers were aligned using an alignment tool that was 3D-printed with sub-micron resolution using direct laser writing. Indium deposition on the carbon fibers, followed by low-temperature microsoldering, provided a robust and reliable method of electrical connection to the polyimide interconnect. Spontaneous multiunit activity and stimulation-evoked compound responses with SNR  >10 and  >120, respectively, were recorded from a small (125 µm) peripheral nerve. We also improved the typically poor charge injection capacity of small diameter carbon fibers by electrodepositing 100 nm-thick iridium oxide films, making the carbon fiber arrays usable for electrical stimulation as well as recording. Our innovations in fabrication technique pave the way for further miniaturization of carbon fiber ultra-microelectrode arrays. We believe these advances to be key steps to enable a shift from labor intensive, manual assembly to a more automated manufacturing process.

Neuronal activity in the globus pallidus internus in patients with tics.

PubMed

Zhuang, P; Hallett, M; Zhang, X; Li, J; Zhang, Y; Li, Y

2009-10-01

To explore the role of neuronal activity in the globus pallidus internus (GPi) in the generation of tic movements. 8 patients with Tourette's syndrome with medically intractable tics who underwent a unilateral pallidotomy for severe tics were studied. They ranged in age from 17 to 24 years; disease duration was 7-19 years. Microelectrode recording was performed in the GPi. The electromyogram (EMG) was simultaneously recorded in muscle groups appropriate for the patient's tics. The relationship between neuronal firing pattern and the EMG was studied. 232 neurons were recorded during tics from eight trajectories. Of these neurons, in addition to decreased neuronal firing rate and irregular firing pattern, 105 (45%) were tic related showing either a burst of activity or a pause in ongoing tonic activity. They could be synchronous (n = 75), earlier than EMG onset (n = 27) or following EMG onset (n = 3). The GPi neuronal bursts preceded EMG onset with decreased (n = 6) or increased activity (n = 21). The initial change in neural activity occurred about 50 ms to 2 s before the EMG onset. Although the data are descriptive and preliminary, the tic related neuronal activity observed in GPi appears to indicate that the basal ganglia motor circuit is involved in tic movements. The early neuronal activity seen in GPi may reflect premonitory sensations that precede a tic.

Method of analysis of local neuronal circuits in the vertebrate central nervous system.

PubMed

Reinis, S; Weiss, D S; McGaraughty, S; Tsoukatos, J

1992-06-01

Although a considerable amount of knowledge has been accumulated about the activity of individual nerve cells in the brain, little is known about their mutual interactions at the local level. The method presented in this paper allows the reconstruction of functional relations within a group of neurons as recorded by a single microelectrode. Data are sampled at 10 or 13 kHz. Prominent spikes produced by one or more single cells are selected and sorted by K-means cluster analysis. The activities of single cells are then related to the background firing of neurons in their vicinity. Auto-correlograms of the leading cells, auto-correlograms of the background cells (mass correlograms) and cross-correlograms between these two levels of firing are computed and evaluated. The statistical probability of mutual interactions is determined, and the statistically significant, most common interspike intervals are stored and attributed to real pairs of spikes in the original record. Selected pairs of spikes, characterized by statistically significant intervals between them, are then assembled into a working model of the system. This method has revealed substantial differences between the information processing in the visual cortex, the inferior colliculus, the rostral ventromedial medulla and the ventrobasal complex of the thalamus. Even short 1-s records of the multiple neuronal activity may provide meaningful and statistically significant results.

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.

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.

Interdigitated microelectrode (IME) impedance sensor for the detection of viable Salmonella typhimurium.

PubMed

Yang, Liju; Li, Yanbin; Griffis, Carl L; Johnson, Michael G

2004-05-15

Interdigitated microelectrodes (IMEs) were used as impedance sensors for rapid detection of viable Salmonella typhimurium in a selective medium and milk samples. The impedance growth curves, impedance against bacterial growth time, were recorded at four frequencies (10Hz, 100Hz, 1kHz, and 10kHz) during the growth of S. typhimurium. The impedance did not change until the cell number reached 10(5)-10(6) CFUml(-1). The greatest change in impedance was observed at 10Hz. To better understand the mechanism of the IME impedance sensor, an equivalent electrical circuit, consisting of double layer capacitors, a dielectric capacitor, and a medium resistor, was introduced and used for interpreting the change in impedance during bacterial growth. Bacterial attachment to the electrode surface was observed with scanning electron microscopy, and it had effect on the impedance measurement. The detection time, t(D), defined as the time for the impedance to start change, was obtained from the impedance growth curve at 10Hz and had a linear relationship with the logarithmic value of the initial cell number of S. typhimurium in the medium and milk samples. The regression equations for the cell numbers between 4.8 and 5.4 x 10(5) CFUml(-1) were t(D) = -1.38 log N + 10.18 with R(2) = 0.99 in the pure medium and t(D) = -1.54 log N + 11.33 with R(2) = 0.98 in milk samples, respectively. The detection times for 4.8 and 5.4 x 10(5) CFUml(-1) initial cell numbers were 9.3 and 2.2 h, respectively, and the detection limit could be as low as 1 cell in a sample.

Simultaneous electrical recording of cardiac electrophysiology and contraction on chip

DOE PAGES

Qian, Fang; Huang, Chao; Lin, Yi-Dong; ...

2017-04-18

Prevailing commercialized cardiac platforms for in vitro drug development utilize planar microelectrode arrays to map action potentials, or impedance sensing to record contraction in real time, but cannot record both functions on the same chip with high spatial resolution. We report a novel cardiac platform that can record cardiac tissue adhesion, electrophysiology, and contractility on the same chip. The platform integrates two independent yet interpenetrating sensor arrays: a microelectrode array for field potential readouts and an interdigitated electrode array for impedance readouts. Together, these arrays provide real-time, non-invasive data acquisition of both cardiac electrophysiology and contractility under physiological conditions andmore » under drug stimuli. Furthermore, we cultured human induced pluripotent stem cell-derived cardiomyocytes as a model system, and used to validate the platform with an excitation–contraction decoupling chemical. Preliminary data using the platform to investigate the effect of the drug norepinephrine are combined with computational efforts. Finally, this platform provides a quantitative and predictive assay system that can potentially be used for comprehensive assessment of cardiac toxicity earlier in the drug discovery process.« less

Simultaneous electrical recording of cardiac electrophysiology and contraction on chip

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

Qian, Fang; Huang, Chao; Lin, Yi-Dong

Prevailing commercialized cardiac platforms for in vitro drug development utilize planar microelectrode arrays to map action potentials, or impedance sensing to record contraction in real time, but cannot record both functions on the same chip with high spatial resolution. We report a novel cardiac platform that can record cardiac tissue adhesion, electrophysiology, and contractility on the same chip. The platform integrates two independent yet interpenetrating sensor arrays: a microelectrode array for field potential readouts and an interdigitated electrode array for impedance readouts. Together, these arrays provide real-time, non-invasive data acquisition of both cardiac electrophysiology and contractility under physiological conditions andmore » under drug stimuli. Furthermore, we cultured human induced pluripotent stem cell-derived cardiomyocytes as a model system, and used to validate the platform with an excitation–contraction decoupling chemical. Preliminary data using the platform to investigate the effect of the drug norepinephrine are combined with computational efforts. Finally, this platform provides a quantitative and predictive assay system that can potentially be used for comprehensive assessment of cardiac toxicity earlier in the drug discovery process.« less

Micro-electro-fluidic grids for nematodes: a lens-less, image-sensor-less approach for on-chip tracking of nematode locomotion.

PubMed

Liu, Peng; Martin, Richard J; Dong, Liang

2013-02-21

This paper reports on the development of a lens-less and image-sensor-less micro-electro-fluidic (MEF) approach for real-time monitoring of the locomotion of microscopic nematodes. The technology showed promise for overcoming the constraint of the limited field of view of conventional optical microscopy, with relatively low cost, good spatial resolution, and high portability. The core of the device was microelectrode grids formed by orthogonally arranging two identical arrays of microelectrode lines. The two microelectrode arrays were spaced by a microfluidic chamber containing a liquid medium of interest. As a nematode (e.g., Caenorhabditis elegans) moved inside the chamber, the invasion of part of its body into some intersection regions between the microelectrodes caused changes in the electrical resistance of these intersection regions. The worm's presence at, or absence from, a detection unit was determined by a comparison between the measured resistance variation of this unit and a pre-defined threshold resistance variation. An electronic readout circuit was designed to address all the detection units and read out their individual electrical resistances. By this means, it was possible to obtain the electrical resistance profile of the whole MEF grid, and thus, the physical pattern of the swimming nematode. We studied the influence of a worm's body on the resistance of an addressed unit. We also investigated how the full-frame scanning and readout rates of the electronic circuit and the dimensions of a detection unit posed an impact on the spatial resolution of the reconstructed images of the nematode. Other important issues, such as the manufacturing-induced initial non-uniformity of the grids and the electrotaxic behaviour of nematodes, were also studied. A drug resistance screening experiment was conducted by using the grids with a good resolution of 30 × 30 μm(2). The phenotypic differences in the locomotion behaviours (e.g., moving speed and oscillation frequency extracted from the reconstructed images with the help of software) between the wild-type (N2) and mutant (lev-8) C. elegans worms in response to different doses of the anthelmintic drug, levamisole, were investigated. The locomotive parameters obtained by the MEF grids agreed well with those obtained by optical microscopy. Therefore, this technology will benefit whole-animal assays by providing a structurally simple, potentially cost-effective device capable of tracking the movement and phenotypes of important nematodes in various microenvironments.

3D plasmonic nanoantennas integrated with MEA biosensors.

PubMed

Dipalo, Michele; Messina, Gabriele C; Amin, Hayder; La Rocca, Rosanna; Shalabaeva, Victoria; Simi, Alessandro; Maccione, Alessandro; Zilio, Pierfrancesco; Berdondini, Luca; De Angelis, Francesco

2015-02-28

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.

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.

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

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

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.

Application of active electrode compensation to perform continuous voltage-clamp recordings with sharp microelectrodes.

PubMed

Gómez-González, J F; Destexhe, A; Bal, T

2014-10-01

Electrophysiological recordings of single neurons in brain tissues are very common in neuroscience. Glass microelectrodes filled with an electrolyte are used to impale the cell membrane in order to record the membrane potential or to inject current. Their high resistance induces a high voltage drop when passing current and it is essential to correct the voltage measurements. In particular, for voltage clamping, the traditional alternatives are two-electrode voltage-clamp technique or discontinuous single electrode voltage-clamp (dSEVC). Nevertheless, it is generally difficult to impale two electrodes in a same neuron and the switching frequency is limited to low frequencies in the case of dSEVC. We present a novel fully computer-implemented alternative to perform continuous voltage-clamp recordings with a single sharp-electrode. To reach such voltage-clamp recordings, we combine an active electrode compensation algorithm (AEC) with a digital controller (AECVC). We applied two types of control-systems: a linear controller (proportional plus integrative controller) and a model-based controller (optimal control). We compared the performance of the two methods to dSEVC using a dynamic model cell and experiments in brain slices. The AECVC method provides an entirely digital method to perform continuous recording and smooth switching between voltage-clamp, current clamp or dynamic-clamp configurations without introducing artifacts.

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.

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

Micro-field evoked potentials recorded from the porcine sub-dural cortical surface utilizing a microelectrode array.

PubMed

Kitzmiller, Joseph P; Hansford, Derek J; Fortin, Linda D; Obrietan, Karl H; Bergdall, Valerie K; Beversdorf, David Q

2007-05-15

A sub-dural surface microelectrode array designed to detect micro-field evoked potentials has been developed. The device is comprised of an array of 350-microm square gold contacts, with bidirectional spacing of 150 microm, contained within a polyimide Kapton material. Cytotoxicity testing suggests that the device is suitable for use with animal and human patients. Implementation of the device in animal studies revealed that reliable evoked potentials could be acquired. Further work will be needed to determine how these micro-field potentials, which demonstrate selectivity for one eye, relate to the distribution of the ocular dominance columns of the occipital cortex.

Micro-Field Evoked Potentials Recorded from the Porcine Sub-Dural Cortical Surface Utilizing a Microelectrode Array

PubMed Central

Kitzmiller, Joseph P.; Hansford, Derek J.; Fortin, Linda D.; Obrietan, Karl H.; Bergdall, Valerie K.

2007-01-01

A sub-dural surface microelectrode array designed to detect microfield evoked potentials has been developed. The device is comprised of an array of 350-micron square gold contacts, with bi-directional spacing of 150 microns, contained within a polyimide Kapton material. Cytotoxicity testing suggests that the device is suitable for use with animal and human patients. Implementation of the device in animal studies revealed that reliable evoked potentials could be acquired. Further work will be needed to determine how these microfield potentials, which demonstrate selectivity for one eye, relate to the distribution of the ocular dominance columns of the occipital cortex. PMID:17298849

Unsupervised neural spike sorting for high-density microelectrode arrays with convolutive independent component analysis.

PubMed

Leibig, Christian; Wachtler, Thomas; Zeck, Günther

2016-09-15

Unsupervised identification of action potentials in multi-channel extracellular recordings, in particular from high-density microelectrode arrays with thousands of sensors, is an unresolved problem. While independent component analysis (ICA) achieves rapid unsupervised sorting, it ignores the convolutive structure of extracellular data, thus limiting the unmixing to a subset of neurons. Here we present a spike sorting algorithm based on convolutive ICA (cICA) to retrieve a larger number of accurately sorted neurons than with instantaneous ICA while accounting for signal overlaps. Spike sorting was applied to datasets with varying signal-to-noise ratios (SNR: 3-12) and 27% spike overlaps, sampled at either 11.5 or 23kHz on 4365 electrodes. We demonstrate how the instantaneity assumption in ICA-based algorithms has to be relaxed in order to improve the spike sorting performance for high-density microelectrode array recordings. Reformulating the convolutive mixture as an instantaneous mixture by modeling several delayed samples jointly is necessary to increase signal-to-noise ratio. Our results emphasize that different cICA algorithms are not equivalent. Spike sorting performance was assessed with ground-truth data generated from experimentally derived templates. The presented spike sorter was able to extract ≈90% of the true spike trains with an error rate below 2%. It was superior to two alternative (c)ICA methods (≈80% accurately sorted neurons) and comparable to a supervised sorting. Our new algorithm represents a fast solution to overcome the current bottleneck in spike sorting of large datasets generated by simultaneous recording with thousands of electrodes. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Programmable high-output-impedance, large-voltage compliance, microstimulator for low-voltage biomedical applications.

PubMed

Farahmand, Sina; Maghami, Mohammad Hossein; Sodagar, Amir M

2012-01-01

This paper reports on the design of a programmable, high output impedance, large voltage compliance microstimulator for low-voltage biomedical applications. A 6-bit binary-weighted digital to analog converter (DAC) is used to generate biphasic stimulus current pulses. A compact current mirror with large output voltage compliance and high output resistance conveys the current pulses to the target tissue. Designed and simulated in a standard 0.18µm CMOS process, the microstimulator circuit is capable of delivering a maximum stimulation current of 160µA to a 10-kΩ resistive load. Operated at a 1.8-V supply voltage, the output stage exhibits a voltage compliance of 1.69V and output resistance of 160MΩ at full scale stimulus current. Layout of the core microelectrode circuit measures 25.5µm×31.5µm.

Ictal high frequency oscillations distinguish two types of seizure territories in humans

PubMed Central

Weiss, Shennan A.; Banks, Garrett P.; McKhann, Guy M.; Goodman, Robert R.; Emerson, Ronald G.; Trevelyan, Andrew J.

2013-01-01

High frequency oscillations have been proposed as a clinically useful biomarker of seizure generating sites. We used a unique set of human microelectrode array recordings (four patients, 10 seizures), in which propagating seizure wavefronts could be readily identified, to investigate the basis of ictal high frequency activity at the cortical (subdural) surface. Sustained, repetitive transient increases in high gamma (80–150 Hz) amplitude, phase-locked to the low-frequency (1–25 Hz) ictal rhythm, correlated with strong multi-unit firing bursts synchronized across the core territory of the seizure. These repetitive high frequency oscillations were seen in recordings from subdural electrodes adjacent to the microelectrode array several seconds after seizure onset, following ictal wavefront passage. Conversely, microelectrode recordings demonstrating only low-level, heterogeneous neural firing correlated with a lack of high frequency oscillations in adjacent subdural recording sites, despite the presence of a strong low-frequency signature. Previously, we reported that this pattern indicates a failure of the seizure to invade the area, because of a feedforward inhibitory veto mechanism. Because multi-unit firing rate and high gamma amplitude are closely related, high frequency oscillations can be used as a surrogate marker to distinguish the core seizure territory from the surrounding penumbra. We developed an efficient measure to detect delayed-onset, sustained ictal high frequency oscillations based on cross-frequency coupling between high gamma amplitude and the low-frequency (1–25 Hz) ictal rhythm. When applied to the broader subdural recording, this measure consistently predicted the timing or failure of ictal invasion, and revealed a surprisingly small and slowly spreading seizure core surrounded by a far larger penumbral territory. Our findings thus establish an underlying neural mechanism for delayed-onset, sustained ictal high frequency oscillations, and provide a practical, efficient method for using them to identify the small ictal core regions. Our observations suggest that it may be possible to reduce substantially the extent of cortical resections in epilepsy surgery procedures without compromising seizure control. PMID:24176977

A three-dimensional flexible microprobe array for neural recording assembled through electrostatic actuation.

PubMed

Chen, Chang-Hsiao; Chuang, Shih-Chang; Su, Huan-Chieh; Hsu, Wei-Lun; Yew, Tri-Rung; Chang, Yen-Chung; Yeh, Shih-Rung; Yao, Da-Jeng

2011-05-07

We designed, fabricated and tested a novel three-dimensional flexible microprobe to record neural signals of a lateral giant nerve fiber of the escape circuit of an American crayfish. An electrostatic actuation folded planar probes into three-dimensional neural probes with arbitrary orientations for neuroscientific applications. A batch assembly based on electrostatic forces simplified the fabrication and was non-toxic. A novel fabrication for these three-dimensional flexible probes used SU-8 and Parylene technology. The mechanical strength of the neural probe was great enough to penetrate into a bio-gel. A flexible probe both decreased the micromotion and alleviated tissue encapsulation of the implant caused by chronic inflammation of tissue when an animal breathes or moves. The cortex consisted of six horizontal layers, and the neurons of the cortex were arranged in vertical structures; the three-dimensional microelectrode arrays were suitable to investigate the cooperative activity for neurons in horizontal separate layers and in vertical cortical columns. With this flexible probe we recorded neural signals of a lateral giant cell from an American crayfish. The response amplitude of action potentials was about 343 µV during 1 ms period; the average recorded data had a ratio of signal to noise as great as 30.22 ± 3.58 dB. The improved performance of this electrode made feasible the separation of neural signals according to their distinct shapes. The cytotoxicity indicated a satisfactory biocompatibility and non-toxicity of the flexible device fabricated in this work. © The Royal Society of Chemistry 2011

A new extracellular multirecording system for electrophysiological studies: application to hippocampal organotypic cultures.

PubMed

Stoppini, L; Duport, S; Corrèges, P

1997-03-01

The present paper describes a new multirecording device which performs continuous electrophysiological studies on organotypic cultures. This device is formed by a card (Physiocard) carrying the culture which is inserted into an electronic module. Electrical activities are recorded by an array of 30 biocompatible microelectrodes which are adjusted into close contact with the upper surface of the slice culture. The microelectrode array is integrated into the card enabling electrical stimulation and recording of neurons over periods ranging from several hours to a few days outside a Faraday cage. Neuronal responses are recorded and analyzed by a dedicated electronic and acquisition chain. A perfusion chamber is contained in the card, allowing continuous perfusion in sterile conditions. Electrophysiological extracellular recordings and some drugs' effects obtained with this system in hippocampal slice cultures were identical to conventional electrophysiological set-up results with tetrodotoxin, bicuculline, kainate, dexamethasone and NBQX. The Physiocard system allows new insights for studies on nervous tissue and allows sophisticated approaches to be used quicker and more easily. It could be used for various neurophysiological studies or screening tests such as neural network mapping, nervous recovery, epilepsy, neurotoxicity or neuropharmacology.

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.

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.

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.

A CMOS IC-based multisite measuring system for stimulation and recording in neural preparations in vitro

PubMed Central

Tateno, Takashi; Nishikawa, Jun

2014-01-01

In this report, we describe the system integration of a complementary metal oxide semiconductor (CMOS) integrated circuit (IC) chip, capable of both stimulation and recording of neurons or neural tissues, to investigate electrical signal propagation within cellular networks in vitro. The overall system consisted of three major subunits: a 5.0 × 5.0 mm CMOS IC chip, a reconfigurable logic device (field-programmable gate array, FPGA), and a PC. To test the system, microelectrode arrays (MEAs) were used to extracellularly measure the activity of cultured rat cortical neurons and mouse cortical slices. The MEA had 64 bidirectional (stimulation and recording) electrodes. In addition, the CMOS IC chip was equipped with dedicated analog filters, amplification stages, and a stimulation buffer. Signals from the electrodes were sampled at 15.6 kHz with 16-bit resolution. The measured input-referred circuitry noise was 10.1 μ V root mean square (10 Hz to 100 kHz), which allowed reliable detection of neural signals ranging from several millivolts down to approximately 33 μ Vpp. Experiments were performed involving the stimulation of neurons with several spatiotemporal patterns and the recording of the triggered activity. An advantage over current MEAs, as demonstrated by our experiments, includes the ability to stimulate (voltage stimulation, 5-bit resolution) spatiotemporal patterns in arbitrary subsets of electrodes. Furthermore, the fast stimulation reset mechanism allowed us to record neuronal signals from a stimulating electrode around 3 ms after stimulation. We demonstrate that the system can be directly applied to, for example, auditory neural prostheses in conjunction with an acoustic sensor and a sound processing system. PMID:25346683

A CMOS IC-based multisite measuring system for stimulation and recording in neural preparations in vitro.

PubMed

Tateno, Takashi; Nishikawa, Jun

2014-01-01

In this report, we describe the system integration of a complementary metal oxide semiconductor (CMOS) integrated circuit (IC) chip, capable of both stimulation and recording of neurons or neural tissues, to investigate electrical signal propagation within cellular networks in vitro. The overall system consisted of three major subunits: a 5.0 × 5.0 mm CMOS IC chip, a reconfigurable logic device (field-programmable gate array, FPGA), and a PC. To test the system, microelectrode arrays (MEAs) were used to extracellularly measure the activity of cultured rat cortical neurons and mouse cortical slices. The MEA had 64 bidirectional (stimulation and recording) electrodes. In addition, the CMOS IC chip was equipped with dedicated analog filters, amplification stages, and a stimulation buffer. Signals from the electrodes were sampled at 15.6 kHz with 16-bit resolution. The measured input-referred circuitry noise was 10.1 μ V root mean square (10 Hz to 100 kHz), which allowed reliable detection of neural signals ranging from several millivolts down to approximately 33 μ Vpp. Experiments were performed involving the stimulation of neurons with several spatiotemporal patterns and the recording of the triggered activity. An advantage over current MEAs, as demonstrated by our experiments, includes the ability to stimulate (voltage stimulation, 5-bit resolution) spatiotemporal patterns in arbitrary subsets of electrodes. Furthermore, the fast stimulation reset mechanism allowed us to record neuronal signals from a stimulating electrode around 3 ms after stimulation. We demonstrate that the system can be directly applied to, for example, auditory neural prostheses in conjunction with an acoustic sensor and a sound processing system.

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.

On-chip, multisite extracellular and intracellular recordings from primary cultured skeletal myotubes

PubMed Central

Rabieh, Noha; Ojovan, Silviya M.; Shmoel, Nava; Erez, Hadas; Maydan, Eilon; Spira, Micha E.

2016-01-01

In contrast to the extensive use of microelectrode array (MEA) technology in electrophysiological studies of cultured neurons and cardiac muscles, the vast field of skeletal muscle research has yet to adopt the technology. Here we demonstrate an empowering MEA technology for high quality, multisite, long-term electrophysiological recordings from cultured skeletal myotubes. Individual rat skeletal myotubes cultured on micrometer sized gold mushroom-shaped microelectrode (gMμE) based MEA tightly engulf the gMμEs, forming a high seal resistance between the myotubes and the gMμEs. As a consequence, spontaneous action potentials generated by the contracting myotubes are recorded as extracellular field potentials with amplitudes of up to 10 mV for over 14 days. Application of a 10 ms, 0.5–0.9 V voltage pulse through the gMμEs electroporated the myotube membrane, and transiently converted the extracellular to intracellular recording mode for 10–30 min. In a fraction of the cultures stable attenuated intracellular recordings were spontaneously produced. In these cases or after electroporation, subthreshold spontaneous potentials were also recorded. The introduction of the gMμE-MEA as a simple-to-use, high-quality electrophysiological tool together with the progress made in the use of cultured human myotubes opens up new venues for basic and clinical skeletal muscle research, preclinical drug screening, and personalized medicine. PMID:27812002

Multi-scale analysis of neural activity in humans: Implications for micro-scale electrocorticography.

PubMed

Kellis, Spencer; Sorensen, Larry; Darvas, Felix; Sayres, Conor; O'Neill, Kevin; Brown, Richard B; House, Paul; Ojemann, Jeff; Greger, Bradley

2016-01-01

Electrocorticography grids have been used to study and diagnose neural pathophysiology for over 50 years, and recently have been used for various neural prosthetic applications. Here we provide evidence that micro-scale electrodes are better suited for studying cortical pathology and function, and for implementing neural prostheses. This work compares dynamics in space, time, and frequency of cortical field potentials recorded by three types of electrodes: electrocorticographic (ECoG) electrodes, non-penetrating micro-ECoG (μECoG) electrodes that use microelectrodes and have tighter interelectrode spacing; and penetrating microelectrodes (MEA) that penetrate the cortex to record single- or multiunit activity (SUA or MUA) and local field potentials (LFP). While the finest spatial scales are found in LFPs recorded intracortically, we found that LFP recorded from μECoG electrodes demonstrate scales of linear similarity (i.e., correlation, coherence, and phase) closer to the intracortical electrodes than the clinical ECoG electrodes. We conclude that LFPs can be recorded intracortically and epicortically at finer scales than clinical ECoG electrodes are capable of capturing. Recorded with appropriately scaled electrodes and grids, field potentials expose a more detailed representation of cortical network activity, enabling advanced analyses of cortical pathology and demanding applications such as brain-computer interfaces. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Burst and Principal Components Analyses of MEA Data Separates Chemicals by Class

EPA Science Inventory

Microelectrode arrays (MEAs) detect drug and chemical induced changes in action potential "spikes" in neuronal networks and can be used to screen chemicals for neurotoxicity. Analytical "fingerprinting," using Principal Components Analysis (PCA) on spike trains recorded from prim...

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

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.

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.

Restoring motor control and sensory feedback in people with upper extremity amputations using arrays of 96 microelectrodes implanted in the median and ulnar nerves.

PubMed

Davis, T S; Wark, H A C; Hutchinson, D T; Warren, D J; O'Neill, K; Scheinblum, T; Clark, G A; Normann, R A; Greger, B

2016-06-01

An important goal of neuroprosthetic research is to establish bidirectional communication between the user and new prosthetic limbs that are capable of controlling >20 different movements. One strategy for achieving this goal is to interface the prosthetic limb directly with efferent and afferent fibres in the peripheral nervous system using an array of intrafascicular microelectrodes. This approach would provide access to a large number of independent neural pathways for controlling high degree-of-freedom prosthetic limbs, as well as evoking multiple-complex sensory percepts. Utah Slanted Electrode Arrays (USEAs, 96 recording/stimulating electrodes) were implanted for 30 days into the median (Subject 1-M, 31 years post-amputation) or ulnar (Subject 2-U, 1.5 years post-amputation) nerves of two amputees. Neural activity was recorded during intended movements of the subject's phantom fingers and a linear Kalman filter was used to decode the neural data. Microelectrode stimulation of varying amplitudes and frequencies was delivered via single or multiple electrodes to investigate the number, size and quality of sensory percepts that could be evoked. Device performance over time was assessed by measuring: electrode impedances, signal-to-noise ratios (SNRs), stimulation thresholds, number and stability of evoked percepts. The subjects were able to proportionally, control individual fingers of a virtual robotic hand, with 13 different movements decoded offline (r = 0.48) and two movements decoded online. Electrical stimulation across one USEA evoked >80 sensory percepts. Varying the stimulation parameters modulated percept quality. Devices remained intrafascicularly implanted for the duration of the study with no significant changes in the SNRs or percept thresholds. This study demonstrated that an array of 96 microelectrodes can be implanted into the human peripheral nervous system for up to 1 month durations. Such an array could provide intuitive control of a virtual prosthetic hand with broad sensory feedback.

Restoring motor control and sensory feedback in people with upper extremity amputations using arrays of 96 microelectrodes implanted in the median and ulnar nerves

NASA Astrophysics Data System (ADS)

Davis, T. S.; Wark, H. A. C.; Hutchinson, D. T.; Warren, D. J.; O'Neill, K.; Scheinblum, T.; Clark, G. A.; Normann, R. A.; Greger, B.

2016-06-01

Objective. An important goal of neuroprosthetic research is to establish bidirectional communication between the user and new prosthetic limbs that are capable of controlling >20 different movements. One strategy for achieving this goal is to interface the prosthetic limb directly with efferent and afferent fibres in the peripheral nervous system using an array of intrafascicular microelectrodes. This approach would provide access to a large number of independent neural pathways for controlling high degree-of-freedom prosthetic limbs, as well as evoking multiple-complex sensory percepts. Approach. Utah Slanted Electrode Arrays (USEAs, 96 recording/stimulating electrodes) were implanted for 30 days into the median (Subject 1-M, 31 years post-amputation) or ulnar (Subject 2-U, 1.5 years post-amputation) nerves of two amputees. Neural activity was recorded during intended movements of the subject’s phantom fingers and a linear Kalman filter was used to decode the neural data. Microelectrode stimulation of varying amplitudes and frequencies was delivered via single or multiple electrodes to investigate the number, size and quality of sensory percepts that could be evoked. Device performance over time was assessed by measuring: electrode impedances, signal-to-noise ratios (SNRs), stimulation thresholds, number and stability of evoked percepts. Main results. The subjects were able to proportionally, control individual fingers of a virtual robotic hand, with 13 different movements decoded offline (r = 0.48) and two movements decoded online. Electrical stimulation across one USEA evoked >80 sensory percepts. Varying the stimulation parameters modulated percept quality. Devices remained intrafascicularly implanted for the duration of the study with no significant changes in the SNRs or percept thresholds. Significance. This study demonstrated that an array of 96 microelectrodes can be implanted into the human peripheral nervous system for up to 1 month durations. Such an array could provide intuitive control of a virtual prosthetic hand with broad sensory feedback.

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.

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

Amorphous silicon carbide ultramicroelectrode arrays for neural stimulation and recording

NASA Astrophysics Data System (ADS)

Deku, Felix; Cohen, Yarden; Joshi-Imre, Alexandra; Kanneganti, Aswini; Gardner, Timothy J.; Cogan, Stuart F.

2018-02-01

Objective. Foreign body response to indwelling cortical microelectrodes limits the reliability of neural stimulation and recording, particularly for extended chronic applications in behaving animals. The extent to which this response compromises the chronic stability of neural devices depends on many factors including the materials used in the electrode construction, the size, and geometry of the indwelling structure. Here, we report on the development of microelectrode arrays (MEAs) based on amorphous silicon carbide (a-SiC). Approach. This technology utilizes a-SiC for its chronic stability and employs semiconductor manufacturing processes to create MEAs with small shank dimensions. The a-SiC films were deposited by plasma enhanced chemical vapor deposition and patterned by thin-film photolithographic techniques. To improve stimulation and recording capabilities with small contact areas, we investigated low impedance coatings on the electrode sites. The assembled devices were characterized in phosphate buffered saline for their electrochemical properties. Main results. MEAs utilizing a-SiC as both the primary structural element and encapsulation were fabricated successfully. These a-SiC MEAs had 16 penetrating shanks. Each shank has a cross-sectional area less than 60 µm2 and electrode sites with a geometric surface area varying from 20 to 200 µm2. Electrode coatings of TiN and SIROF reduced 1 kHz electrode impedance to less than 100 kΩ from ~2.8 MΩ for 100 µm2 Au electrode sites and increased the charge injection capacities to values greater than 3 mC cm‑2. Finally, we demonstrated functionality by recording neural activity from basal ganglia nucleus of Zebra Finches and motor cortex of rat. Significance. The a-SiC MEAs provide a significant advancement in the development of microelectrodes that over the years has relied on silicon platforms for device manufacture. These flexible a-SiC MEAs have the potential for decreased tissue damage and reduced foreign body response. The technique is promising and has potential for clinical translation and large scale manufacturing.

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.

Drug release from porous silicon for stable neural interface

NASA Astrophysics Data System (ADS)

Sun, Tao; Tsang, Wei Mong; Park, Woo-Tae

2014-02-01

70 μm-thick porous Si (PSi) layer with the pore size of 11.1 ± 7.6 nm was formed on an 8-in. Si wafer via an anodization process for the microfabrication of a microelectrode to record neural signals. To reduce host tissue responses to the microelectrode and achieve a stable neural interface, water-soluble dexamethesone (Dex) was loaded into the PSi via incubation with the drug solution overnight. After the drug loading process, the pore size of PSi reduced to 4.7 ± 2.6 nm on the basis of scanning electron microscopic (SEM) images, while its wettability was remarkably enhanced. Fluorescence images demonstrated that Dex was loaded into the porous structure of the PSi. Degradation rate of the PSi was investigated by incubation in distilled water for 21 days. Moreover, the drug release profile of the Dex-loaded PSi was a combination of an initial burst release and subsequent sustained release. To evaluate cellular responses to the drug release from the PSi, primary astrocytes were seeded on the surface of samples. After 2 days of culture, the Dex-loaded PSi could not only moderately prevent astrocyte adhesion in comparison with Si, but also more effectively suppress the activation of primary astrocytes than unloaded PSi due to the drug release. Therefore, it might be an effective method to reduce host tissue responses and stabilize the quality of the recorded neural signal by means of loading drugs into the PSi component of the microelectrode.

Asymmetric pallidal neuronal activity in patients with cervical dystonia

PubMed Central

Moll, Christian K. E.; Galindo-Leon, Edgar; Sharott, Andrew; Gulberti, Alessandro; Buhmann, Carsten; Koeppen, Johannes A.; Biermann, Maxine; Bäumer, Tobias; Zittel, Simone; Westphal, Manfred; Gerloff, Christian; Hamel, Wolfgang; Münchau, Alexander; Engel, Andreas K.

2014-01-01

The origin of asymmetric clinical manifestation of symptoms in patients suffering from cervical dystonia (CD) is hitherto poorly understood. Dysregulated neuronal activity in the basal ganglia has been suggested to have a role in the pathophysiology of CD. Here, we re-assessed the question to what extent relative changes occur in the direct vs. indirect basal ganglia pathway in CD, whether these circuit changes are lateralized, and how these alterations relate to CD symptoms. To this end, we recorded ongoing single cell and local field potential (LFP) activity from the external (GPe) and internal pallidal segment (GPi) of 13 CD patients undergoing microelectrode-guided stereotactic surgery for deep brain stimulation in the GPi. We compared pallidal recordings from CD patients operated under local anaesthesia (LA) with those obtained in CD patients operated under general anaesthesia (GA). In awake patients, mean GPe discharge rate (52 Hz) was lower than that of GPi (72 Hz). Mean GPi discharge ipsilateral to the side of head turning was higher than contralateral and correlated with torticollis symptom severity. Lateralized differences were absent at the level of the GPe and in recordings from patients operated under GA. Furthermore, in the GPi of CD patients there was a subpopulation of theta-oscillatory cells with unique bursting characteristics. Power and coherence of GPe– and GPi–LFPs were dominated by a theta peak and also exhibited band-specific interhemispheric differences. Strong cross-frequency coupling of low-gamma amplitude to theta phase was a feature of pallidal LFPs recorded under LA, but not GA. These results indicate that CD is associated with an asymmetric pallidal outflow. Based on the finding of symmetric neuronal discharges in the GPe, we propose that an imbalanced interhemispheric direct pathway gain may be involved in CD pathophysiology. PMID:24574981

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.

Neural hijacking: action of high-frequency electrical stimulation on cortical circuits.

PubMed

Cheney, P D; Griffin, D M; Van Acker, G M

2013-10-01

Electrical stimulation of the brain was one of the first experimental methods applied to understanding brain organization and function and it continues as a highly useful method both in research and clinical applications. Intracortical microstimulation (ICMS) involves applying electrical stimuli through a microelectrode suitable for recording the action potentials of single neurons. ICMS can be categorized into single-pulse stimulation; high-frequency, short-duration stimulation; and high-frequency, long-duration stimulation. For clinical and experimental reasons, considerable interest focuses on the mechanism of neural activation by electrical stimuli. In this article, we discuss recent results suggesting that action potentials evoked in cortical neurons by high-frequency electrical stimulation do not sum with the natural, behaviorally related background activity; rather, high-frequency stimulation eliminates and replaces natural activity. We refer to this as neural hijacking. We propose that a major component of the mechanism underlying neural hijacking is excitation of axons by ICMS and elimination of natural spikes by antidromic collision with stimulus-driven spikes evoked at high frequency. Evidence also supports neural hijacking as an important mechanism underlying the action of deep brain stimulation in the subthalamic nucleus and its therapeutic effect in treating Parkinson's disease.

Miniature electrometer preamplifier effectively compensates for input capacitance

NASA Technical Reports Server (NTRS)

Burrous, C. N.; Deboo, G. J.

1966-01-01

Negative capacitance preamplifier using a dual MOS /Metal Oxide Silicon/ transistor in conjunction with bipolar transistors is used with intracellular microelectrodes in recording bioelectric potentials. Applications would include use as a pickup plate video amplifier in storage tube tests and for pH and ionization chamber measurements.

Streaming potentials in gramicidin channels measured with ion-selective microelectrodes.

PubMed Central

Tripathi, S; Hladky, S B

1998-01-01

Streaming potentials have been measured for gramicidin channels with a new method employing ion-selective microelectrodes. It is shown that ideally ion-selective electrodes placed at the membrane surface record the true streaming potential. Using this method for ion concentrations below 100 mM, approximately seven water molecules are transported whenever a sodium, potassium, or cesium ion, passes through the channel. This new method confirms earlier measurements (Rosenberg, P.A., and A. Finkelstein. 1978. Interaction of ions and water in gramicidin A channels. J. Gen. Physiol. 72:327-340) in which the streaming potentials were calculated as the difference between electrical potentials measured in the presence of gramicidin and in the presence of the ion carriers valinomycin and nonactin. PMID:9635745

Neuroelectronics and modeling of electrical signals for monitoring and control of Parkinson's disease

NASA Astrophysics Data System (ADS)

Chintakuntla, Ritesh R.; Abraham, Jose K.; Varadan, Vijay K.

2009-03-01

The brain and the human nervous system are perhaps the most researched but least understood components of the human body. This is so because of the complex nature of its working and the high density of functions. The monitoring of neural signals could help one better understand the working of the brain and newer recording and monitoring methods have been developed ever since it was discovered that the brain communicates internally by means of electrical pulses. Neuroelectronics is the field which deals with the interface between electronics or semiconductors to living neurons. This includes monitoring of electrical activity from the brain as well as the development of feedback devices for stimulation of parts of the brain for treatment of disorders. In this paper these electrical signals are modeled through a nano/microelectrode arrays based on the electronic equivalent model using Cadence PSD 15.0. The results were compared with those previously published models such as Kupfmuller and Jenik's model, McGrogan's Neuron Model which are based on the Hodgkin and Huxley model. We have developed and equivalent circuit model using discrete passive components to simulate the electrical activity of the neurons. The simulated circuit can be easily be modified by adding some more ionic channels and the results can be used to predict necessary external stimulus needed for stimulation of neurons affected by the Parkinson's disease (PD). Implementing such a model in PD patients could predict the necessary voltages required for the electrical stimulation of the sub-thalamus region for the control tremor motion.

Decoding spoken words using local field potentials recorded from the cortical surface

NASA Astrophysics Data System (ADS)

Kellis, Spencer; Miller, Kai; Thomson, Kyle; Brown, Richard; House, Paul; Greger, Bradley

2010-10-01

Pathological conditions such as amyotrophic lateral sclerosis or damage to the brainstem can leave patients severely paralyzed but fully aware, in a condition known as 'locked-in syndrome'. Communication in this state is often reduced to selecting individual letters or words by arduous residual movements. More intuitive and rapid communication may be restored by directly interfacing with language areas of the cerebral cortex. We used a grid of closely spaced, nonpenetrating micro-electrodes to record local field potentials (LFPs) from the surface of face motor cortex and Wernicke's area. From these LFPs we were successful in classifying a small set of words on a trial-by-trial basis at levels well above chance. We found that the pattern of electrodes with the highest accuracy changed for each word, which supports the idea that closely spaced micro-electrodes are capable of capturing neural signals from independent neural processing assemblies. These results further support using cortical surface potentials (electrocorticography) in brain-computer interfaces. These results also show that LFPs recorded from the cortical surface (micro-electrocorticography) of language areas can be used to classify speech-related cortical rhythms and potentially restore communication to locked-in patients.

Signal processing methods for reducing artifacts in microelectrode brain recordings caused by functional electrical stimulation

NASA Astrophysics Data System (ADS)

Young, D.; Willett, F.; Memberg, W. D.; Murphy, B.; Walter, B.; Sweet, J.; Miller, J.; Hochberg, L. R.; Kirsch, R. F.; Ajiboye, A. B.

2018-04-01

Objective. Functional electrical stimulation (FES) is a promising technology for restoring movement to paralyzed limbs. Intracortical brain-computer interfaces (iBCIs) have enabled intuitive control over virtual and robotic movements, and more recently over upper extremity FES neuroprostheses. However, electrical stimulation of muscles creates artifacts in intracortical microelectrode recordings that could degrade iBCI performance. Here, we investigate methods for reducing the cortically recorded artifacts that result from peripheral electrical stimulation. Approach. One participant in the BrainGate2 pilot clinical trial had two intracortical microelectrode arrays placed in the motor cortex, and thirty-six stimulating intramuscular electrodes placed in the muscles of the contralateral limb. We characterized intracortically recorded electrical artifacts during both intramuscular and surface stimulation. We compared the performance of three artifact reduction methods: blanking, common average reference (CAR) and linear regression reference (LRR), which creates channel-specific reference signals, composed of weighted sums of other channels. Main results. Electrical artifacts resulting from surface stimulation were 175  ×  larger than baseline neural recordings (which were 110 µV peak-to-peak), while intramuscular stimulation artifacts were only 4  ×  larger. The artifact waveforms were highly consistent across electrodes within each array. Application of LRR reduced artifact magnitudes to less than 10 µV and largely preserved the original neural feature values used for decoding. Unmitigated stimulation artifacts decreased iBCI decoding performance, but performance was almost completely recovered using LRR, which outperformed CAR and blanking and extracted useful neural information during stimulation artifact periods. Significance. The LRR method was effective at reducing electrical artifacts resulting from both intramuscular and surface FES, and almost completely restored iBCI decoding performance (>90% recovery for surface stimulation and full recovery for intramuscular stimulation). The results demonstrate that FES-induced artifacts can be easily mitigated in FES  +  iBCI systems by using LRR for artifact reduction, and suggest that the LRR method may also be useful in other noise reduction applications.

Highly sensitive three-dimensional interdigitated microelectrode for microparticle detection using electrical impedance spectroscopy

NASA Astrophysics Data System (ADS)

Chang, Fu-Yu; Chen, Ming-Kun; Wang, Min-Haw; Jang, Ling-Sheng

2016-02-01

Cell impedance analysis is widely used for monitoring biological and medical reactions. In this study, a highly sensitive three-dimensional (3D) interdigitated microelectrode (IME) with a high aspect ratio on a polyimide (PI) flexible substrate was fabricated for microparticle detection (e.g. cell quantity detection) using electroforming and lithography technology. 3D finite element simulations were performed to compare the performance of the 3D IME (in terms of sensitivity and signal-to-noise ratio) to that of a planar IME for particles in the sensing area. Various quantities of particles were captured in Dulbecco’s modified Eagle medium and their impedances were measured. With the 3D IME, the particles were arranged in the gap, not on the electrode, avoiding the noise due to particle position. For the maximum particle quantities, the results show that the 3D IME has at least 5-fold higher sensitivity than that of the planar IME. The trends of impedance magnitude and phase due to particle quantity were verified using the equivalent circuit model. The impedance (1269 Ω) of 69 particles was used to estimate the particle quantity (68 particles) with 98.6% accuracy using a parabolic regression curve at 500 kHz.

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.

Developmental excitatory-to-inhibitory GABA polarity switch is delayed in Ts65Dn mice, a genetic model of Down syndrome.

PubMed

Lysenko, Larisa V; Kim, Jeesun; Madamba, Francisco; Tyrtyshnaia, Anna A; Ruparelia, Aarti; Kleschevnikov, Alexander M

2018-07-01

Down syndrome (DS) is the most frequent genetic cause of developmental abnormalities leading to intellectual disability. One notable phenomenon affecting the formation of nascent neural circuits during late developmental periods is developmental switch of GABA action from depolarizing to hyperpolarizing mode. We examined properties of this switch in DS using primary cultures and acute hippocampal slices from Ts65Dn mice, a genetic model of DS. Cultures of DIV3-DIV13 Ts65Dn and control normosomic (2 N) neurons were loaded with FURA-2 AM, and GABA action was assessed using local applications. In 2 N cultures, the number of GABA-activated cells dropped from ~100% to 20% between postnatal days 3-13 (P3-P13) reflecting the switch in GABA action polarity. In Ts65Dn cultures, the timing of this switch was delayed by 2-3 days. Next, microelectrode recordings of multi-unit activity (MUA) were performed in CA3 slices during bath application of the GABA A agonist isoguvacine. MUA frequency was increased in P8-P12 and reduced in P14-P22 slices reflecting the switch of GABA action from excitatory to inhibitory mode. The timing of this switch was delayed in Ts65Dn by approximately 2 days. Finally, frequency of giant depolarizing potentials (GDPs), a form of primordial neural activity, was significantly increased in slices from Ts65Dn pups at P12 and P14. These experimental evidences show that GABA action polarity switch is delayed in Ts65Dn model of DS, and that these changes lead to a delay in maturation of nascent neural circuits. These alterations may affect properties of neural circuits in adult animals and, therefore, represent a prospective target for pharmacotherapy of cognitive impairment in DS. Copyright © 2018 Elsevier Inc. 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.

Synaptic activation of putative sensory neurons by hexamethonium-sensitive nerve pathways in mouse colon.

PubMed

Hibberd, Timothy J; Travis, Lee; Wiklendt, Lukasz; Costa, Marcello; Brookes, Simon J H; Hu, Hongzhen; Keating, Damien J; Spencer, Nick J

2018-01-01

The gastrointestinal tract contains its own independent population of sensory neurons within the gut wall. These sensory neurons have been referred to as intrinsic primary afferent neurons (IPANs) and can be identified by immunoreactivity to calcitonin gene-related peptide (CGRP) in mice. A common feature of IPANs is a paucity of fast synaptic inputs observed during sharp microelectrode recordings. Whether this is observed using different recording techniques is of particular interest for understanding the physiology of these neurons and neural circuit modeling. Here, we imaged spontaneous and evoked activation of myenteric neurons in isolated whole preparations of mouse colon and correlated recordings with CGRP and nitric oxide synthase (NOS) immunoreactivity, post hoc. Calcium indicator fluo 4 was used for this purpose. Calcium responses were recorded in nerve cell bodies located 5-10 mm oral to transmural electrical nerve stimuli. A total of 618 recorded neurons were classified for CGRP or NOS immunoreactivity. Aboral electrical stimulation evoked short-latency calcium transients in the majority of myenteric neurons, including ~90% of CGRP-immunoreactive Dogiel type II neurons. Activation of Dogiel type II neurons had a time course consistent with fast synaptic transmission and was always abolished by hexamethonium (300 μM) and by low-calcium Krebs solution. The nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium iodide (during synaptic blockade) directly activated Dogiel type II neurons. The present study suggests that murine colonic Dogiel type II neurons receive prominent fast excitatory synaptic inputs from hexamethonium-sensitive neural pathways. NEW & NOTEWORTHY Myenteric neurons in isolated mouse colon were recorded using calcium imaging and then neurochemically defined. Short-latency calcium transients were detected in >90% of calcitonin gene-related peptide-immunoreactive neurons to electrical stimulation of hexamethonium-sensitive pathways. Putative sensory Dogiel type II calcitonin gene-related peptide-immunoreactive myenteric neurons may receive widespread fast synaptic inputs in mouse colon.

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.

Electroporation followed by electrochemical measurement of quantal transmitter release from single cells using a patterned microelectrode.

PubMed

Ghosh, Jaya; Liu, Xin; Gillis, Kevin D

2013-06-07

An electrochemical microelectrode located immediately adjacent to a single neuroendocrine cell can record spikes of amperometric current that result from exocytosis of oxidizable transmitter from individual vesicles, i.e., quantal exocytosis. Here, we report the development of an efficient method where the same electrochemical microelectrode is used to electropermeabilize an adjacent chromaffin cell and then measure the consequent quantal catecholamine release using amperometry. Trains of voltage pulses, 5-7 V in amplitude and 0.1-0.2 ms in duration, were used to reliably trigger release from cells using gold electrodes. Amperometric spikes induced by electropermeabilization had similar areas, peak heights and durations as amperometric spikes elicited by depolarizing high K(+) solutions, therefore release occurs from individual secretory granules. Uptake of trypan blue stain into cells demonstrated that the plasma membrane is permeabilized by the voltage stimulus. Voltage pulses did not degrade the electrochemical sensitivity of the electrodes assayed using a test analyte. Surprisingly, robust quantal release was elicited upon electroporation in the absence of Ca(2+) in the bath solution (0 Ca(2+)/5 mM EGTA). In contrast, electropermeabilization-induced transmitter release required Cl(-) in the bath solution in that bracketed experiments demonstrated a steep dependence of the rate of electropermeabilization-induced transmitter release on [Cl(-)] between 2 and 32 mM. Using the same electrochemical electrode to electroporate and record quantal release of catecholamines from an individual chromaffin cell allows precise timing of the stimulus, stimulation of a single cell at a time, and can be used to load membrane-impermeant substances into a cell.

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.

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

Maximum Acceleration Recording Circuit

NASA Technical Reports Server (NTRS)

Bozeman, Richard J., Jr.

1995-01-01

Coarsely digitized maximum levels recorded in blown fuses. Circuit feeds power to accelerometer and makes nonvolatile record of maximum level to which output of accelerometer rises during measurement interval. In comparison with inertia-type single-preset-trip-point mechanical maximum-acceleration-recording devices, circuit weighs less, occupies less space, and records accelerations within narrower bands of uncertainty. In comparison with prior electronic data-acquisition systems designed for same purpose, circuit simpler, less bulky, consumes less power, costs and analysis of data recorded in magnetic or electronic memory devices. Circuit used, for example, to record accelerations to which commodities subjected during transportation on trucks.

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

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

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.

Light-induced pH changes in the intact retinae of normal and early diabetic rats

PubMed Central

Dmitriev, Andrey V.; Henderson, Desmond; Linsenmeier, Robert A.

2016-01-01

Double-barreled H+-selective microelectrodes were used to measure local extracellular concentration of H+ ([H+]o) in the retina of dark-adapted anesthetized Long-Evans rats. The microelectrode advanced in steps of 30 μm throughout the retina from the vitreal surface to retinal pigment epithelium and then to the choroid, recording changes in [H+]o evoked by light stimulation. Recordings were performed in diabetic rats 1 to 3 months after intraperitoneal injection of streptozotocin and the results were compared with data obtained in age-matched control animals. Brief light stimulation (2.5 s) evoked changes of [H+]o with amplitudes of a few nM. Throughout the retina, there was a transient initial acidification for ~200 ms followed by steady alkalinization, although amplitudes and kinetics of these components were slightly variable in different retinal layers. No significant difference was found when the light-induced [H+]o changes recorded in various retinal layers of early diabetic rats were compared with the [H+]o changes from corresponding layers of control animals. Also, when H+-selective microelectrodes were located in the retinal pigment epithelium (RPE) layer, an increase in H+ was recorded, whose time course and amplitude were similar in control and diabetic rats. However, a striking difference between light-induced [H+]o changes in controls and diabetics was observed in the choriocapillaris, in the thin layer (10 – 20 μm) distal to the basal membrane of the RPE. In control rats, choroidal [H+]o decreased in a few cases, but much more often practically did not change. In contrast, diabetic rats demonstrated either an increase (in half of the cases) or no change in choroidal [H+]o. The data suggest that the active participation of the choroidal blood supply in stabilization of [H+]o could be partially compromised already at early stages of diabetes in rats. Interestingly, it appeared that the acid removal by the choroidal circulation was compromised most after 1 month of diabetes and tended to improve later. PMID:26639389

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

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.

Signal transfer within a cultured asymmetric cortical neuron circuit

NASA Astrophysics Data System (ADS)

Isomura, Takuya; Shimba, Kenta; Takayama, Yuzo; Takeuchi, Akimasa; Kotani, Kiyoshi; Jimbo, Yasuhiko

2015-12-01

Objective. Simplified neuronal circuits are required for investigating information representation in nervous systems and for validating theoretical neural network models. Here, we developed patterned neuronal circuits using micro fabricated devices, comprising a micro-well array bonded to a microelectrode-array substrate. Approach. The micro-well array consisted of micrometre-scale wells connected by tunnels, all contained within a silicone slab called a micro-chamber. The design of the micro-chamber confined somata to the wells and allowed axons to grow through the tunnels bidirectionally but with a designed, unidirectional bias. We guided axons into the point of the arrow structure where one of the two tunnel entrances is located, making that the preferred direction. Main results. When rat cortical neurons were cultured in the wells, their axons grew through the tunnels and connected to neurons in adjoining wells. Unidirectional burst transfers and other asymmetric signal-propagation phenomena were observed via the substrate-embedded electrodes. Seventy-nine percent of burst transfers were in the forward direction. We also observed rapid propagation of activity from sites of local electrical stimulation, and significant effects of inhibitory synapse blockade on bursting activity. Significance. These results suggest that this simple, substrate-controlled neuronal circuit can be applied to develop in vitro models of the function of cortical microcircuits or deep neural networks, better to elucidate the laws governing the dynamics of neuronal networks.

Signal transfer within a cultured asymmetric cortical neuron circuit.

PubMed

Isomura, Takuya; Shimba, Kenta; Takayama, Yuzo; Takeuchi, Akimasa; Kotani, Kiyoshi; Jimbo, Yasuhiko

2015-12-01

Simplified neuronal circuits are required for investigating information representation in nervous systems and for validating theoretical neural network models. Here, we developed patterned neuronal circuits using micro fabricated devices, comprising a micro-well array bonded to a microelectrode-array substrate. The micro-well array consisted of micrometre-scale wells connected by tunnels, all contained within a silicone slab called a micro-chamber. The design of the micro-chamber confined somata to the wells and allowed axons to grow through the tunnels bidirectionally but with a designed, unidirectional bias. We guided axons into the point of the arrow structure where one of the two tunnel entrances is located, making that the preferred direction. When rat cortical neurons were cultured in the wells, their axons grew through the tunnels and connected to neurons in adjoining wells. Unidirectional burst transfers and other asymmetric signal-propagation phenomena were observed via the substrate-embedded electrodes. Seventy-nine percent of burst transfers were in the forward direction. We also observed rapid propagation of activity from sites of local electrical stimulation, and significant effects of inhibitory synapse blockade on bursting activity. These results suggest that this simple, substrate-controlled neuronal circuit can be applied to develop in vitro models of the function of cortical microcircuits or deep neural networks, better to elucidate the laws governing the dynamics of neuronal networks.

A perforated CMOS microchip for immobilization and activity monitoring of electrogenic cells

NASA Astrophysics Data System (ADS)

Greve, F.; Lichtenberg, J.; Kirstein, K.-U.; Frey, U.; Perriard, J.-C.; Hierlemann, A.

2007-03-01

CMOS-based microelectrode systems offer decisive advantages over conventional micro-electrode arrays, which include the possibility to perform on-chip signal conditioning or to efficiently use larger numbers of electrodes to obtain statistically relevant data, e.g., in pharmacological drug screening. A larger number of electrodes can only be realized with the help of on-chip multiplexing and readout schemes, which require integrated electronics. Another fundamental issue in performing high-fidelity recordings from electrogenic cells is a good electrical coupling between the cells and the microelectrodes, in particular, since the recorded extracellular signals are in the range of only 10-1000 µV. In this paper we present the first CMOS microelectrode system with integrated micromechanical cell-placement features fabricated in a commercial CMOS process with subsequent post-CMOS bulk micromachining. This new microdevice aims at enabling the precise placement of single cells in the center of the electrodes to ensure an efficient use of the available electrodes, even for low-density cell cultures. Small through-chip holes have been generated at the metal-electrode sites by using a combination of bulk micromachining and reactive-ion etching. These holes act as orifices so that cell immobilization can be achieved by means of pneumatic anchoring. The chip additionally hosts integrated circuitry, i.e., multiplexers to select the respective readout electrodes, an amplifier with selectable gain (2×, 10×, 100×), and a high-pass filter (100 Hz cut-off). In this paper we show that electrical signals from most of the electrodes can be recorded, even in low-density cultures of neonatal rat cardiomyocytes, by using perforated metal electrodes and by applying a small underpressure from the backside of the chip. The measurements evidenced that, in most cases, about 90% of the electrodes were covered with single cells, approximately 4% were covered with more than one cell due to clustering and approximately 6% were not covered with any cell, mostly as a consequence of orifice clogging. After 4 days of culturing, the cells were still in place on the electrodes so that the cell electrical activity could be measured using the on-chip circuitry. Measured signal amplitudes were in the range of 500-700 µV, while the input-referred noise of the readout was below 15 µVrms (100 Hz-4 kHz bandwidth). We report on the development and fabrication of this new cell-biological tool and present first results collected during the characterization and evaluation of the chip. The recordings of electrical potentials of neonatal rat cardiomyocytes after several days in vitro, which, on the one hand, were conventionally cultured (no pneumatic anchoring) and, on the other hand, were anchored and immobilized, will be detailed.

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.

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.

Automated serum chloride analysis using the Apple computer

PubMed Central

Taylor, Paul J.; Bouska, Rosalie A.

1988-01-01

Chloride analysis employing a coulometric technique is a wellestablished method. However, the equipment needed is specialized and somewhat expensive. The purpose of this paper is to report the development of the hardware and software to perform this analysis using an Apple computer to control the coulometric titration, as well as to automate it and to print out the results. The Apple computer is used to control the flow of current in a circuit, which includes silver and platinum electrodes where the following reactions take place: A g → A g + + l e −    ( at silver anode ) 2 H 2 O + 2 e − → 2 O H − + H 2    ( at platinum cathode ) The generated silver ions then react with the chloride ion in the sample to form AgCl. A g + + C l − → A g C l ( s ) When all of the chloride ion has been titrated, the concentration of silver ions in solution increases rapidly, which causes an increase in the current between two silver microelectrodes. This current is converted to a voltage and amplified by a simple circuit. This voltage is read by the analogue-to-digital converter. The computer stops the titration and calculates the chloride ion content of the sample. Thus, the computer controls the apparatus, records the data, and reacts to the data to terminate the analyses and prints out the results and messages to the analyst. Analysis of standards and reference sera indicate the method is rapid, accurate and precise. Application of this apparatus as a teaching aidfor electronics to chemistry and medical students is also described. PMID:18925182

Network interactions within the canine intrinsic cardiac nervous system: implications for reflex control of regional cardiac function

PubMed Central

Beaumont, Eric; Salavatian, Siamak; Southerland, E Marie; Vinet, Alain; Jacquemet, Vincent; Armour, J Andrew; Ardell, Jeffrey L

2013-01-01

The aims of the study were to determine how aggregates of intrinsic cardiac (IC) neurons transduce the cardiovascular milieu versus responding to changes in central neuronal drive and to determine IC network interactions subsequent to induced neural imbalances in the genesis of atrial fibrillation (AF). Activity from multiple IC neurons in the right atrial ganglionated plexus was recorded in eight anaesthetized canines using a 16-channel linear microelectrode array. Induced changes in IC neuronal activity were evaluated in response to: (1) focal cardiac mechanical distortion; (2) electrical activation of cervical vagi or stellate ganglia; (3) occlusion of the inferior vena cava or thoracic aorta; (4) transient ventricular ischaemia, and (5) neurally induced AF. Low level activity (ranging from 0 to 2.7 Hz) generated by 92 neurons was identified in basal states, activities that displayed functional interconnectivity. The majority (56%) of IC neurons so identified received indirect central inputs (vagus alone: 25%; stellate ganglion alone: 27%; both: 48%). Fifty per cent transduced the cardiac milieu responding to multimodal stressors applied to the great vessels or heart. Fifty per cent of IC neurons exhibited cardiac cycle periodicity, with activity occurring primarily in late diastole into isovolumetric contraction. Cardiac-related activity in IC neurons was primarily related to direct cardiac mechano-sensory inputs and indirect autonomic efferent inputs. In response to mediastinal nerve stimulation, most IC neurons became excessively activated; such network behaviour preceded and persisted throughout AF. It was concluded that stochastic interactions occur among IC local circuit neuronal populations in the control of regional cardiac function. Modulation of IC local circuit neuronal recruitment may represent a novel approach for the treatment of cardiac disease, including atrial arrhythmias. PMID:23818689

Corrosion of Tungsten Microelectrodes used in Neural Recording Applications

PubMed Central

Patrick, Erin; Orazem, Mark E.; Sanchez, Justin C.; Nishida, Toshikazu

2011-01-01

In neuroprosthetic applications, long-term electrode viability is necessary for robust recording of the activity of neural populations used for generating communication and control signals. The corrosion of tungsten microwire electrodes used for intracortical recording applications was analyzed in a controlled bench-top study and compared to the corrosion of tungsten microwires used in an in vivo study. Two electrolytes were investigated for the benchtop electrochemical analysis: 0.9% phosphate buffered saline (PBS) and 0.9% PBS containing 30 mM of hydrogen peroxide. The oxidation and reduction reactions responsible for corrosion were found by measurement of the open circuit potential and analysis of Pourbaix diagrams. Dissolution of tungsten to form the tungstic ion was found to be the corrosion mechanism. The corrosion rate was estimated from the polarization resistance, which was extrapolated from the electrochemical impedance spectroscopy data. The results show that tungsten microwires in an electrolyte of PBS have a corrosion rate of 300–700 µm/yr. The corrosion rate for tungsten microwires in an electrolyte containing PBS and 30 mM H2O2 is accelerated to 10,000–20,000 µm/yr. The corrosion rate was found to be controlled by the concentration of the reacting species in the cathodic reaction (e.g. O2 and H2O2). The in vivo corrosion rate, averaged over the duration of implantation, was estimated to be 100 µm/yr. The reduced in vivo corrosion rate as compared to the benchtop rate is attributed to decreased rate of oxygen diffusion caused by the presence of a biological film and a reduced concentration of available oxygen in the brain. PMID:21470563

Corrosion of tungsten microelectrodes used in neural recording applications.

PubMed

Patrick, Erin; Orazem, Mark E; Sanchez, Justin C; Nishida, Toshikazu

2011-06-15

In neuroprosthetic applications, long-term electrode viability is necessary for robust recording of the activity of neural populations used for generating communication and control signals. The corrosion of tungsten microwire electrodes used for intracortical recording applications was analyzed in a controlled bench-top study and compared to the corrosion of tungsten microwires used in an in vivo study. Two electrolytes were investigated for the bench-top electrochemical analysis: 0.9% phosphate buffered saline (PBS) and 0.9% PBS containing 30 mM of hydrogen peroxide. The oxidation and reduction reactions responsible for corrosion were found by measurement of the open circuit potential and analysis of Pourbaix diagrams. Dissolution of tungsten to form the tungstic ion was found to be the corrosion mechanism. The corrosion rate was estimated from the polarization resistance, which was extrapolated from the electrochemical impedance spectroscopy data. The results show that tungsten microwires in an electrolyte of PBS have a corrosion rate of 300-700 μm/yr. The corrosion rate for tungsten microwires in an electrolyte containing PBS and 30 mM H₂O₂ is accelerated to 10,000-20,000 μm/yr. The corrosion rate was found to be controlled by the concentration of the reacting species in the cathodic reaction (e.g. O₂ and H₂O₂). The in vivo corrosion rate, averaged over the duration of implantation, was estimated to be 100 μm/yr. The reduced in vivo corrosion rate as compared to the bench-top rate is attributed to decreased rate of oxygen diffusion caused by the presence of a biological film and a reduced concentration of available oxygen in the brain. Copyright © 2011 Elsevier B.V. All rights reserved.

Reflective lens-free imaging on high-density silicon microelectrode arrays for monitoring and evaluation of in vitro cardiac contractility

PubMed Central

Pauwelyn, Thomas; Stahl, Richard; Mayo, Lakyn; Zheng, Xuan; Lambrechts, Andy; Janssens, Stefan; Lagae, Liesbet; Reumers, Veerle; Braeken, Dries

2018-01-01

The high rate of drug attrition caused by cardiotoxicity is a major challenge for drug development. Here, we developed a reflective lens-free imaging (RLFI) approach to non-invasively record in vitro cell deformation in cardiac monolayers with high temporal (169 fps) and non-reconstructed spatial resolution (352 µm) over a field-of-view of maximally 57 mm2. The method is compatible with opaque surfaces and silicon-based devices. Further, we demonstrated that the system can detect the impairment of both contractility and fast excitation waves in cardiac monolayers. Additionally, the RLFI device was implemented on a CMOS-based microelectrode array to retrieve multi-parametric information of cardiac cells, thereby offering more in-depth analysis of drug-induced (cardiomyopathic) effects for preclinical cardiotoxicity screening applications. PMID:29675322

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

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.

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

Interface design for CMOS-integrated Electrochemical Impedance Spectroscopy (EIS) biosensors.

PubMed

Manickam, Arun; Johnson, Christopher Andrew; Kavusi, Sam; Hassibi, Arjang

2012-10-29

Electrochemical Impedance Spectroscopy (EIS) is a powerful electrochemical technique to detect biomolecules. EIS has the potential of carrying out label-free and real-time detection, and in addition, can be easily implemented using electronic integrated circuits (ICs) that are built through standard semiconductor fabrication processes. This paper focuses on the various design and optimization aspects of EIS ICs, particularly the bio-to-semiconductor interface design. We discuss, in detail, considerations such as the choice of the electrode surface in view of IC manufacturing, surface linkers, and development of optimal bio-molecular detection protocols. We also report experimental results, using both macro- and micro-electrodes to demonstrate the design trade-offs and ultimately validate our optimization procedures.

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

A 1024-Channel CMOS Microelectrode Array With 26,400 Electrodes for Recording and Stimulation of Electrogenic Cells In Vitro

PubMed Central

Ballini, Marco; Müller, Jan; Livi, Paolo; Chen, Yihui; Frey, Urs; Stettler, Alexander; Shadmani, Amir; Viswam, Vijay; Jones, Ian Lloyd; Jäckel, David; Radivojevic, Milos; Lewandowska, Marta K.; Gong, Wei; Fiscella, Michele; Bakkum, Douglas J.; Heer, Flavio; Hierlemann, Andreas

2017-01-01

To advance our understanding of the functioning of neuronal ensembles, systems are needed to enable simultaneous recording from a large number of individual neurons at high spatiotemporal resolution and good signal-to-noise ratio. Moreover, stimulation capability is highly desirable for investigating, for example, plasticity and learning processes. Here, we present a microelectrode array (MEA) system on a single CMOS die for in vitro recording and stimulation. The system incorporates 26,400 platinum electrodes, fabricated by in-house post-processing, over a large sensing area (3.85 × 2.10 mm2) with sub-cellular spatial resolution (pitch of 17.5 μm). Owing to an area and power efficient implementation, we were able to integrate 1024 readout channels on chip to record extracellular signals from a user-specified selection of electrodes. These channels feature noise values of 2.4 μVrms in the action-potential band (300 Hz–10 kHz) and 5.4 μVrms in the local-field-potential band (1 Hz–300 Hz), and provide programmable gain (up to 78 dB) to accommodate various biological preparations. Amplified and filtered signals are digitized by 10 bit parallel single-slope ADCs at 20 kSamples/s. The system also includes 32 stimulation units, which can elicit neural spikes through either current or voltage pulses. The chip consumes only 75 mW in total, which obviates the need of active cooling even for sensitive cell cultures. PMID:28502989

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.

A study of the dynamics of seizure propagation across micro domains in the vicinity of the seizure onset zone

PubMed Central

Basu, Ishita; Kudela, Pawel; Korzeniewska, Anna; Franaszczuk, Piotr J.; Anderson, William S.

2015-01-01

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 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. Approach We used 7 complex partial seizures recorded from 4 patients undergoing intracranial monitoring for surgical evaluation to reconstruct the seizure propagation pattern over sliding windows using a directed transfer function measure. Main results We showed that a directed transfer function can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with known propagation pattern. In general, depending on the location of the micro-electrode grid with respect to the clinical seizure onset zone and the time from seizure onset, ictal propagation changed in directional characteristics over a 2 to 10 seconds time scale, with gross directionality limited to spatial dimensions of approximately 9mm2. 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 seizure onset zone 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. PMID:26061006

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

Design and preparation of open circuit potential biosensor for in vitro and in vivo glucose monitoring.

PubMed

Song, Yonggui; Su, Dan; Shen, Yuan; Liu, Hongyu; Wang, Li

2017-01-01

A novel open circuit potential biosensor (OCPS) composed of a working electrode and a Ag/AgCl reference electrode was designed for in vivo continuous glucose monitoring in this work. The macroporous carbon derived from kenaf stem (KSC) was used to construct a KSC microelectrode (denoted as KSCME) which was subsequently used to load glucose oxidase (GOD) as the working electrode. The resulting GOD/KSCMEs could catalyze the oxidation of glucose directly to result in changes of the open circuit potential (V oc ) of the OCPS. The V oc of OCPS was dependent on the glucose concentration, showing a linear range of 0.03-10.0 mM (R = 0.999) with a detection limit of 10 μM. In addition, the OCPS exhibited good selectivity for glucose over other common endogenous interferences. The feasibility of the proposed OCPS for glucose detection in mice skin tumors and normal tissue homogenate samples (in vitro experiment) and rat subcutaneous glucose monitoring (in vivo experiment) was also demonstrated with satisfactory results. The biosensor represents a novel example of a superficial cancer diagnostic device, and the proposed OCPS also provides new ideas for the development of a simple and highly selective device for continuous glucose sensing.

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.

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.

Design, Fabrication and Characterization of a Low-Impedance 3D Electrode Array System for Neuro-Electrophysiology

PubMed Central

Kusko, Mihaela; Craciunoiu, Florea; Amuzescu, Bogdan; Halitzchi, Ferdinand; Selescu, Tudor; Radoi, Antonio; Popescu, Marian; Simion, Monica; Bragaru, Adina; Ignat, Teodora

2012-01-01

Recent progress in patterned microelectrode manufacturing technology and microfluidics has opened the way to a large variety of cellular and molecular biosensor-based applications. In this extremely diverse and rapidly expanding landscape, silicon-based technologies occupy a special position, given their statute of mature, consolidated, and highly accessible areas of development. Within the present work we report microfabrication procedures and workflows for 3D patterned gold-plated microelectrode arrays (MEA) of different shapes (pyramidal, conical and high aspect ratio), and we provide a detailed characterization of their physical features during all the fabrication steps to have in the end a reliable technology. Moreover, the electrical performances of MEA silicon chips mounted on standardized connector boards via ultrasound wire-bonding have been tested using non-destructive electrochemical methods: linear sweep and cyclic voltammetry, impedance spectroscopy. Further, an experimental recording chamber package suitable for in vitro electrophysiology experiments has been realized using custom-design electronics for electrical stimulus delivery and local field potential recording, included in a complete electrophysiology setup, and the experimental structures have been tested on newborn rat hippocampal slices, yielding similar performance compared to commercially available MEA equipments. PMID:23208555

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.

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.

Neural correlates of high-gamma oscillations (60–200 Hz) in macaque local field potentials and their potential implications in electrocorticography

PubMed Central

Crone, Nathan E.; Niebur, Ernst; Franaszczuk, Piotr J.; Hsiao, Steven S.

2009-01-01

Recent studies using electrocorticographic (ECoG) recordings in humans have shown that functional activation of cortex is associated with an increase in power in the high-gamma frequency range (∼60–200 Hz). Here we investigate the neural correlates of this high-gamma activity in local field potential (LFP). Single units and LFP were recorded with microelectrodes from the hand region of macaque SII cortex while vibrotactile stimuli of varying intensities were presented to the hand. We found that high-gamma power in the LFP was strongly correlated with the average firing rate recorded by the microelectrodes, both temporally and on a trial-by-trial basis. In comparison, the correlation between firing rate and low-gamma power (40–80 Hz) was much smaller. In order to explore the potential effects of neuronal firing on ECoG, we developed a model to estimate ECoG power generated by different firing patterns of the underlying cortical population and studied how ECoG power varies with changes in firing rate versus the degree of synchronous firing between neurons in the population. Both an increase in firing rate and neuronal synchrony increased high-gamma power in the simulated ECoG data. However, ECoG high-gamma activity was much more sensitive to increases in neuronal synchrony than firing rate. PMID:18987189

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

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

Structure-property relationships in the optimization of polysilicon thin films for electrical recording/stimulation of single neurons.

PubMed

Saha, Rajarshi; Muthuswamy, Jit

2007-06-01

We had earlier demonstrated the use of polysilicon microelectrodes for recording electrical activity from single neurons in vivo. Good machinability and compatibility with CMOS processing further make polysilicon an attractive interface material between biological environments on one hand and MEMS technology and digital circuits on the other hand. In this study, we focus on optimizing the polysilicon thin films for (a) electrical recording and (b) stimulation of single neurons by minimizing its electrochemical impedance spectra and maximizing its charge storage/injection capacity respectively. The structure-property relationships in ion-implanted (phosphorus) LPCVD polysilicon thin films under different annealing and doping conditions were carefully assessed during this optimization process. A 2D model of the polysilicon thin film consisting of 4 grains and 3 grain boundaries was constructed and the effect of grain size and grain boundaries on dc resistivity was simulated using device simulator ATLAS. Optimal processing conditions and doping concentrations resulted in a 10-fold decrease in electrochemical impedance from 1.1 kOmega to 0.1 kOmega at 1 kHz (area of polysilicon interface = 4.8 mm(2)). Subsequent characterizations showed that evolution of secondary grains within the polysilicon thin films at optimal doping and annealing conditions (10(21)/cm(3) of phosphorus and annealed at 1200 degrees C) was responsible for decreasing the impedance. Cyclic voltammetry studies demonstrated that charge storage properties of low doped (10(15)/cm(3)) thin films was 111.4 microC/cm(2) in phosphate buffered saline which compares well with platinum wires (approximately 50 microC/cm(2)) and the double-layered capacitance (C(dl)) could be sustained between -1 to 1 V before breakdown and hydrolysis. We conclude that polysilicon can be optimized for recording and stimulating single neurons and can be a valuable interface material between neurons and CMOS or MEMS devices.

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

Electrothermal Microactuators With Peg Drive Improve Performance for Brain Implant Applications

PubMed Central

Anand, Sindhu; Sutanto, Jemmy; Baker, Michael S.; Okandan, Murat; Muthuswamy, Jit

2013-01-01

This paper presents a new actuation scheme for in-plane bidirectional translation of polysilicon microelectrodes. The new Chevron-peg actuation scheme uses microelectromechanical systems (MEMS) based electrothermal microactuators to move microelectrodes for brain implant applications. The design changes were motivated by specific needs identified by the in vivo testing of an earlier generation of MEMS microelectrodes that were actuated by the Chevron-latch type of mechanism. The microelectrodes actuated by the Chevron-peg mechanism discussed here show improved performance in the following key areas: higher force generation capability (111 μN per heat strip compared to 50 μN), reduced power consumption (91 mW compared to 360 mW), and reliable performance with consistent forward and backward movements of microelectrodes. Failure analysis of the Chevron-latch and the Chevron-peg type of actuation schemes showed that the latter is more robust to wear over four million cycles of operation. The parameters for the activation waveforms for Chevron-peg actuators were optimized using statistical analysis. Waveforms with a 1-ms time period and a 1-Hz frequency of operation showed minimal error between the expected and the actual movement of the microelectrodes. The new generation of Chevron-peg actuators and microelectrodes are therefore expected to enhance the longevity and performance of implanted microelectrodes in the brain.  [2011-0341] PMID:24431926

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...

Impedimetric method for measuring ultra-low E. coli concentrations in human urine.

PubMed

Settu, Kalpana; Chen, Ching-Jung; Liu, Jen-Tsai; Chen, Chien-Lung; Tsai, Jang-Zern

2015-04-15

In this study, we developed an interdigitated gold microelectrode-based impedance sensor to detect Escherichia coli (E. coli) in human urine samples for urinary tract infection (UTI) diagnosis. E. coli growth in human urine samples was successfully monitored during a 12-h culture, and the results showed that the maximum relative changes could be measured at 10Hz. An equivalent electrical circuit model was used for evaluating the variations in impedance characteristics of bacterial growth. The equivalent circuit analysis indicated that the change in impedance values at low frequencies was caused by double layer capacitance due to bacterial attachment and formation of biofilm on electrode surface in urine. A linear relationship between the impedance change and initial E. coli concentration was obtained with the coefficient of determination R(2)>0.90 at various growth times of 1, 3, 5, 7, 9 and 12h in urine. Thus our sensor is capable of detecting a wide range of E. coli concentration, 7×10(0) to 7×10(8) cells/ml, in urine samples with high sensitivity. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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.

A portable microelectrode array recording system incorporating cultured neuronal networks for neurotoxin detection.

PubMed

Pancrazio, Joseph J; Gray, Samuel A; Shubin, Yura S; Kulagina, Nadezhda; Cuttino, David S; Shaffer, Kara M; Eisemann, Kevin; Curran, Anthony; Zim, Bret; Gross, Guenter W; O'Shaughnessy, Thomas J

2003-10-01

Cultured neuronal networks, which have the capacity to respond to a wide range of neuroactive compounds, have been suggested to be useful for both screening known analytes and unknown compounds for acute neuropharmacologic effects. Extracellular recording from cultured neuronal networks provides a means for extracting physiologically relevant activity, i.e. action potential firing, in a noninvasive manner conducive for long-term measurements. Previous work from our laboratory described prototype portable systems capable of high signal-to-noise extracellular recordings from cardiac myocytes. The present work describes a portable system tailored to monitoring neuronal extracellular potentials that readily incorporates standardized microelectrode arrays developed by and in use at the University of North Texas. This system utilizes low noise amplifier and filter boards, a two-stage thermal control system with integrated fluidics and a graphical user interface for data acquisition and control implemented on a personal computer. Wherever possible, off-the-shelf components have been utilized for system design and fabrication. During use with cultured neuronal networks, the system typically exhibits input referred noise levels of only 4-6 microVRMS, such that extracellular potentials exceeding 40 microV can be readily resolved. A flow rate of up to 1 ml/min was achieved while the cell recording chamber temperature was maintained within a range of 36-37 degrees C. To demonstrate the capability of this system to resolve small extracellular potentials, pharmacological experiments with cultured neuronal networks have been performed using ion channel blockers, tetrodotoxin and tityustoxin. The implications of the experiments for neurotoxin detection are discussed.

A Computerized Microelectrode Recording to Magnetic Resonance Imaging Mapping System for Subthalamic Nucleus Deep Brain Stimulation Surgery.

PubMed

Dodani, Sunjay S; Lu, Charles W; Aldridge, J Wayne; Chou, Kelvin L; Patil, Parag G

2018-06-01

Accurate electrode placement is critical to the success of deep brain stimulation (DBS) surgery. Suboptimal targeting may arise from poor initial target localization, frame-based targeting error, or intraoperative brain shift. These uncertainties can make DBS surgery challenging. To develop a computerized system to guide subthalamic nucleus (STN) DBS electrode localization and to estimate the trajectory of intraoperative microelectrode recording (MER) on magnetic resonance (MR) images algorithmically during DBS surgery. Our method is based upon the relationship between the high-frequency band (HFB; 500-2000 Hz) signal from MER and voxel intensity on MR images. The HFB profile along an MER trajectory recorded during surgery is compared to voxel intensity profiles along many potential trajectories in the region of the surgically planned trajectory. From these comparisons of HFB recordings and potential trajectories, an estimate of the MER trajectory is calculated. This calculated trajectory is then compared to actual trajectory, as estimated by postoperative high-resolution computed tomography. We compared 20 planned, calculated, and actual trajectories in 13 patients who underwent STN DBS surgery. Targeting errors for our calculated trajectories (2.33 mm ± 0.2 mm) were significantly less than errors for surgically planned trajectories (2.83 mm ± 0.2 mm; P = .01), improving targeting prediction in 70% of individual cases (14/20). Moreover, in 4 of 4 initial MER trajectories that missed the STN, our method correctly indicated the required direction of targeting adjustment for the DBS lead to intersect the STN. A computer-based algorithm simultaneously utilizing MER and MR information potentially eases electrode localization during STN DBS surgery.

A novel carbon tipped single micro-optrode for combined optogenetics and electrophysiology

PubMed Central

Vizvári, Attila D.; Bali, Zsolt K.; Márki, Balázs; Nagy, Lili V.; Kónya, Zoltán; Madarász, Dániel; Henn-Mike, Nóra; Varga, Csaba; Hernádi, István

2018-01-01

Optical microelectrodes (optrodes) are used in neuroscience to transmit light into the brain of a genetically modified animal to evoke and record electrical activity from light-sensitive neurons. Our novel micro-optrode solution integrates a light-transmitting 125 micrometer optical fiber and a 9 micrometer carbon monofilament to form an electrical lead element, which is contained in a borosilicate glass sheathing coaxial arrangement ending with a micrometer-sized carbon tip. This novel unit design is stiff and slender enough to be used for targeting deep brain areas, and may cause less tissue damage compared with previous models. The center-positioned carbon fiber is less prone to light-induced artifacts than side-lit metal microelectrodes previously presented. The carbon tip is capable of not only recording electrical signals of neuronal origin but can also provide valuable surface area for electron transfer, which is essential in electrochemical (voltammetry, amperometry) or microbiosensor applications. We present details of design and manufacture as well as operational examples of the newly developed single micro-optrode, which includes assessments of 1) carbon tip length–impedance relationship, 2) light transmission capabilities, 3) photoelectric artifacts in carbon fibers, 4) responses to dopamine using fast-scan cyclic voltammetry in vivo, and 5) optogenetic stimulation and spike or local field potential recording from the rat brain transfected with channelrhodopsin-2. With this work, we demonstrate that our novel carbon tipped single micro-optrode may open up new avenues for use in optogenetic stimulation when needing to be combined with extracellular recording, electrochemical, or microbiosensor measurements performed on a millisecond basis. PMID:29513711

Importance of Thickness in Human Cardiomyocyte Network for Effective Electrophysiological Stimulation Using On-Chip Extracellular Microelectrodes

NASA Astrophysics Data System (ADS)

Hamada, Tomoyo; Nomura, Fumimasa; Kaneko, Tomoyuki; Yasuda, Kenji

2012-06-01

We have developed a three-dimensionally controlled in vitro human cardiomyocyte network assay for the measurements of drug-induced conductivity changes and the appearance of fatal arrhythmia such as ventricular tachycardia/fibrillation for more precise in vitro predictive cardiotoxicity. To construct an artificial conductance propagation model of a human cardiomyocyte network, first, we examined the cell concentration dependence of the cell network heights and found the existence of a height limit of cell networks, which was double-layer height, whereas the cardiomyocytes were effectively and homogeneously cultivated within the microchamber maintaining their spatial distribution constant and their electrophysiological conductance and propagation were successfully recorded using a microelectrode array set on the bottom of the microchamber. The pacing ability of a cardiomyocyte's electrophysiological response has been evaluated using microelectrode extracellular stimulation, and the stimulation for pacing also successfully regulated the beating frequencies of two-layered cardiomyocyte networks, whereas monolayered cardiomyocyte networks were hardly stimulated by the external electrodes using the two-layered cardiomyocyte stimulation condition. The stability of the lined-up shape of human cardiomyocytes within the rectangularly arranged agarose microchambers was limited for a two-layered cardiomyocyte network because their stronger force generation shrunk those cells after peeling off the substrate. The results indicate the importance of fabrication technology of thickness control of cellular networks for effective extracellular stimulation and the potential concerning thick cardiomyocyte networks for long-term cultivation.

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.

76 FR 9374 - Proposed Extension of Existing Information Collection; Examinations and Testing of Electrical...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-17

... related detached components; 75.800-4 Testing, examination and maintenance of circuit breakers; record; 75...-4 Testing, examination and maintenance of circuit breakers; record; 75.1001-1 Devices for..., testing, and maintenance; 77.800-2 Testing, examination and maintenance of circuit breakers; record; and...

Recording and Modulation of Epileptiform Activity in Rodent Brain Slices Coupled to Microelectrode Arrays.

PubMed

Panuccio, Gabriella; Colombi, Ilaria; Chiappalone, Michela

2018-05-15

Temporal lobe epilepsy (TLE) is the most common partial complex epileptic syndrome and the least responsive to medications. Deep brain stimulation (DBS) is a promising approach when pharmacological treatment fails or neurosurgery is not recommended. Acute brain slices coupled to microelectrode arrays (MEAs) represent a valuable tool to study neuronal network interactions and their modulation by electrical stimulation. As compared to conventional extracellular recording techniques, they provide the added advantages of a greater number of observation points and a known inter-electrode distance, which allow studying the propagation path and speed of electrophysiological signals. However, tissue oxygenation may be greatly impaired during MEA recording, requiring a high perfusion rate, which comes at the cost of decreased signal-to-noise ratio and higher oscillations in the experimental temperature. Electrical stimulation further stresses the brain tissue, making it difficult to pursue prolonged recording/stimulation epochs. Moreover, electrical modulation of brain slice activity needs to target specific structures/pathways within the brain slice, requiring that electrode mapping be easily and quickly performed live during the experiment. Here, we illustrate how to perform the recording and electrical modulation of 4-aminopyridine (4AP)-induced epileptiform activity in rodent brain slices using planar MEAs. We show that the brain tissue obtained from mice outperforms rat brain tissue and is thus better suited for MEA experiments. This protocol guarantees the generation and maintenance of a stable epileptiform pattern that faithfully reproduces the electrophysiological features observed with conventional field potential recording, persists for several hours, and outlasts sustained electrical stimulation for prolonged epochs. Tissue viability throughout the experiment is achieved thanks to the use of a small-volume custom recording chamber allowing for laminar flow and quick solution exchange even at low (1 mL/min) perfusion rates. Quick MEA mapping for real-time monitoring and selection of stimulating electrodes is performed by a custom graphic user interface (GUI).

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.

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.

QSpike tools: a generic framework for parallel batch preprocessing of extracellular neuronal signals recorded by substrate microelectrode arrays.

PubMed

Mahmud, Mufti; Pulizzi, Rocco; Vasilaki, Eleni; Giugliano, Michele

2014-01-01

Micro-Electrode Arrays (MEAs) have emerged as a mature technique to investigate brain (dys)functions in vivo and in in vitro animal models. Often referred to as "smart" Petri dishes, MEAs have demonstrated a great potential particularly for medium-throughput studies in vitro, both in academic and pharmaceutical industrial contexts. Enabling rapid comparison of ionic/pharmacological/genetic manipulations with control conditions, MEAs are employed to screen compounds by monitoring non-invasively the spontaneous and evoked neuronal electrical activity in longitudinal studies, with relatively inexpensive equipment. However, in order to acquire sufficient statistical significance, recordings last up to tens of minutes and generate large amount of raw data (e.g., 60 channels/MEA, 16 bits A/D conversion, 20 kHz sampling rate: approximately 8 GB/MEA,h uncompressed). Thus, when the experimental conditions to be tested are numerous, the availability of fast, standardized, and automated signal preprocessing becomes pivotal for any subsequent analysis and data archiving. To this aim, we developed an in-house cloud-computing system, named QSpike Tools, where CPU-intensive operations, required for preprocessing of each recorded channel (e.g., filtering, multi-unit activity detection, spike-sorting, etc.), are decomposed and batch-queued to a multi-core architecture or to a computers cluster. With the commercial availability of new and inexpensive high-density MEAs, we believe that disseminating QSpike Tools might facilitate its wide adoption and customization, and inspire the creation of community-supported cloud-computing facilities for MEAs users.

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.

Multiscale Aspects of Generation of High-Gamma Activity during Seizures in Human Neocortex123

PubMed Central

Marcuccilli, Charles J.; Ben-Mabrouk, Faiza; Lew, Sean M.; Goodman, Robert R.; McKhann, Guy M.; Frim, David M.; Kohrman, Michael H.; Schevon, Catherine A.; van Drongelen, Wim

2016-01-01

High-gamma (HG; 80-150 Hz) activity in macroscopic clinical records is considered a marker for critical brain regions involved in seizure initiation; it is correlated with pathological multiunit firing during neocortical seizures in the seizure core, an area identified by correlated multiunit spiking and low frequency seizure activity. However, the effects of the spatiotemporal dynamics of seizure on HG power generation are not well understood. Here, we studied HG generation and propagation, using a three-step, multiscale signal analysis and modeling approach. First, we analyzed concurrent neuronal and microscopic network HG activity in neocortical slices from seven intractable epilepsy patients. We found HG activity in these networks, especially when neurons displayed paroxysmal depolarization shifts and network activity was highly synchronized. Second, we examined HG activity acquired with microelectrode arrays recorded during human seizures (n = 8). We confirmed the presence of synchronized HG power across microelectrode records and the macroscale, both specifically associated with the core region of the seizure. Third, we used volume conduction-based modeling to relate HG activity and network synchrony at different network scales. We showed that local HG oscillations require high levels of synchrony to cross scales, and that this requirement is met at the microscopic scale, but not within macroscopic networks. Instead, we present evidence that HG power at the macroscale may result from harmonics of ongoing seizure activity. Ictal HG power marks the seizure core, but the generating mechanism can differ across spatial scales. PMID:27257623

30 CFR 77.900-2 - Testing, examination, and maintenance of circuit breakers; record.

Code of Federal Regulations, 2011 CFR

2011-07-01

... protecting low- and medium-voltage circuits serving three-phase alternating current equipment and such record... AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits...

30 CFR 77.900-2 - Testing, examination, and maintenance of circuit breakers; record.

Code of Federal Regulations, 2010 CFR

2010-07-01

... protecting low- and medium-voltage circuits serving three-phase alternating current equipment and such record... AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits...

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

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

Decoding 3-D Reach and Grasp Kinematics from High-Frequency Local Field Potentials in Primate Primary Motor Cortex

PubMed Central

Zhuang, Jun; Vargas-Irwin, Carlos; Donoghue, John P.

2011-01-01

Intracortical microelectrode array recordings generate a variety of neural signals with potential application as control signals in neural interface systems. Previous studies have focused on single and multiunit activity, as well as low frequency local field potentials (LFPs), but have not explored higher frequency (>200 Hz) LFPs. In addition, the potential to decode three dimensional (3-D) reach and grasp kinematics based on LFPs has not been demonstrated. Here, we use mutual information and decoding analyses to probe the information content about 3-D reaching and grasping of 7 different LFP frequency bands in the range of 0.3 Hz – 400 Hz. LFPs were recorded via 96-microelectrode arrays in primary motor cortex (M1) of two monkeys performing free reaching to grasp moving objects. Mutual information analyses revealed that higher frequency bands (e.g. 100 – 200 Hz and 200 – 400 Hz) carried the most information about the examined kinematics. Furthermore, Kalman filter decoding revealed that broadband high frequency LFPs, likely reflecting multiunit activity, provided the best decoding performance as well as substantial accuracy in reconstructing reach kinematics, grasp aperture and aperture velocity. These results indicate that LFPs, especially high frequency bands, could be useful signals for neural interfaces controlling 3-D reach and grasp kinematics. PMID:20403782

A Micro-Electrode Array device coupled to a laser-based system for the local stimulation of neurons by optical release of glutamate.

PubMed

Ghezzi, Diego; Menegon, Andrea; Pedrocchi, Alessandra; Valtorta, Flavia; Ferrigno, Giancarlo

2008-10-30

Optical stimulation is a promising approach to investigate the local dynamic responses of cultured neurons. In particular, flash photolysis of caged compounds offers the advantage of allowing the rapid change of concentration of either extracellular or intracellular molecules, such as neurotransmitters or second messengers, for the stimulation or modulation of neuronal activity. We describe here the use of an ultra-violet (UV) laser diode coupled to an optical fibre for the local activation of caged compounds combined with a Micro-Electrode Array (MEA) device. Local uncaging was achieved by UV irradiation through the optical fibre previously positioned by using a red laser diode. The size of the stimulation was determined using caged fluorescein, whereas its efficacy was tested by studying the effect of uncaging the neurotransmitter glutamate. Uncaged glutamate evoked neuronal responses that were recorded using either fluorescence measurements or electrophysiological recordings with MEAs, thus showing the ability of our system to induce local neuronal excitation. This method allows overcoming the limitations of the MEA system related to unfocused electrical stimulation and induction of electrical artefacts. In addition, the coupling of a UV laser diode to an optical fibre allows a precise local stimulation and a quick change of the stimulation point.

Zika virus-induced hyper excitation precedes death of mouse primary neuron.

PubMed

Gaburro, Julie; Bhatti, Asim; Sundaramoorthy, Vinod; Dearnley, Megan; Green, Diane; Nahavandi, Saeid; Paradkar, Prasad N; Duchemin, Jean-Bernard

2018-04-27

Zika virus infection in new born is linked to congenital syndromes, especially microcephaly. Studies have shown that these neuropathies are the result of significant death of neuronal progenitor cells in the central nervous system of the embryo, targeted by the virus. Although cell death via apoptosis is well acknowledged, little is known about possible pathogenic cellular mechanisms triggering cell death in neurons. We used in vitro embryonic mouse primary neuron cultures to study possible upstream cellular mechanisms of cell death. Neuronal networks were grown on microelectrode array and electrical activity was recorded at different times post Zika virus infection. In addition to this method, we used confocal microscopy and Q-PCR techniques to observe morphological and molecular changes after infection. Zika virus infection of mouse primary neurons triggers an early spiking excitation of neuron cultures, followed by dramatic loss of this activity. Using NMDA receptor antagonist, we show that this excitotoxicity mechanism, likely via glutamate, could also contribute to the observed nervous system defects in human embryos and could open new perspective regarding the causes of adult neuropathies. This model of excitotoxicity, in the context of neurotropic virus infection, highlights the significance of neuronal activity recording with microelectrode array and possibility of more than one lethal mechanism after Zika virus infection in the nervous system.

Laminar Profile of Spontaneous and Evoked Theta: Rhythmic Modulation of Cortical Processing During Word Integration

PubMed Central

Halgren, Eric; Kaestner, Erik; Marinkovic, Ksenija; Cash, Sydney S.; Wang, Chunmao; Schomer, Donald L.; Madsen, Joseph R.; Ulbert, Istvan

2015-01-01

Theta may play a central role during language understanding and other extended cognitive processing, providing an envelope for widespread integration of participating cortical areas. We used linear microelectrode arrays in epileptics to define the circuits generating theta in inferotemporal, perirhinal, entorhinal, prefrontal and anterior cingulate cortices. In all locations, theta was generated by excitatory current sinks in middle layers which receive predominantly feedforward inputs, alternating with sinks in superficial layers which receive mainly feedback/associative inputs. Baseline and event-related theta were generated by indistinguishable laminar profiles of transmembrane currents and unit-firing. Word presentation could reset theta phase, permitting theta to contribute to late event-related potentials, even when theta power decreases relative to baseline. Limited recordings during sentence reading are consistent with rhythmic theta activity entrained by a given word modulating the neural background for the following word. These findings show that theta occurs spontaneously, and can be momentarily suppressed, reset and synchronized by words. Theta represents an alternation between feedforward/divergent and associative/convergent processing modes that may temporally organize sustained processing and optimize the timing of memory formation. We suggest that words are initially encoded via a ventral feedforward stream which is lexicosemantic in the anteroventral temporal lobe; its arrival may trigger a widespread theta rhythm which integrates the word within a larger context. PMID:25801916

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

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

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.

Biophysics of microchannel-enabled neuron-electrode interfaces.

PubMed

Wang, Ling; Riss, Michael; Buitrago, Jennifer Olmos; Claverol-Tinturé, Enric

2012-04-01

We have previously described the use of microchannels (μChannels) as substrate-integrated equivalents of micropipettes and advantageous neuron-electrode interface enhancers. The use of μChannels to establish stable recording and stimulation of threading axons results in a high signal-to-noise ratio (SNR), potentially high-throughput and low-cost alternative to conventional substrate-embedded microelectrodes. Here we confirm the consistent achievement of high SNRs with μChannels and systematically characterize the impact of μChannel geometry on the measured signals via numerical simulations and in vitro experiments. We demonstrate and rationalize how channels with a length of ≤300 μm and channel cross section of ≤12 μm(2) support spontaneous formation of seals and yield spike sizes in the millivolt range. Despite the low degree of complexity involved in their fabrication and use, μChannel devices provide a single-unit mean SNR of 101 ± 76, which compares favourably with the SNR obtained from typical microelectrode arrays.

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

A 32-channel fully implantable wireless neurosensor for simultaneous recording from two cortical regions.

PubMed

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

2011-01-01

We present a fully implantable, wireless, neurosensor for multiple-location neural interface applications. The device integrates two independent 16-channel intracortical microelectrode arrays and can simultaneously acquire 32 channels of broadband neural data from two separate cortical areas. The system-on-chip implantable sensor is built on a flexible Kapton polymer substrate and incorporates three very low power subunits: two cortical subunits connected to a common subcutaneous subunit. Each cortical subunit has an ultra-low power 16-channel preamplifier and multiplexer integrated onto a cortical microelectrode array. The subcutaneous epicranial unit has an inductively coupled power supply, two analog-to-digital converters, a low power digital controller chip, and microlaser-based infrared telemetry. The entire system is soft encapsulated with biocompatible flexible materials for in vivo applications. Broadband neural data is conditioned, amplified, and analog multiplexed by each of the cortical subunits and passed to the subcutaneous component, where it is digitized and combined with synchronization data and wirelessly transmitted transcutaneously using high speed infrared telemetry.

Amperometric Self-Referencing Ceramic Based Microelectrode Arrays for D-Serine Detection.

PubMed

Campos-Beltrán, Diana; Konradsson-Geuken, Åsa; Quintero, Jorge E; Marshall, Lisa

2018-03-06

D-serine is the major D-amino acid in the mammalian central nervous system. As the dominant co-agonist of the endogenous synaptic NMDA receptor, D-serine plays a role in synaptic plasticity, learning, and memory. Alterations in D-serine are linked to neuropsychiatric disorders including schizophrenia. Thus, it is of increasing interest to monitor the concentration of D-serine in vivo as a relevant player in dynamic neuron-glia network activity. Here we present a procedure for amperometric detection of D-serine with self-referencing ceramic-based microelectrode arrays (MEAs) coated with D-amino acid oxidase from the yeast Rhodotorula gracilis (RgDAAO). We demonstrate in vitro D-serine recordings with a mean sensitivity of 8.61 ± 0.83 pA/µM to D-serine, a limit of detection (LOD) of 0.17 ± 0.01 µM, and a selectivity ratio of 80:1 or greater for D-serine over ascorbic acid (mean ± SEM; n = 12) that can be used for freely moving studies.

30 CFR 75.900-4 - Testing, examination, and maintenance of circuit breakers; record.

Code of Federal Regulations, 2011 CFR

2011-07-01

... circuits serving three-phase alternating current equipment used in the mine. Such record shall be kept in a... Underground Low- and Medium-Voltage Alternating Current Circuits § 75.900-4 Testing, examination, and...

30 CFR 75.900-4 - Testing, examination, and maintenance of circuit breakers; record.

Code of Federal Regulations, 2010 CFR

2010-07-01

... circuits serving three-phase alternating current equipment used in the mine. Such record shall be kept in a... Underground Low- and Medium-Voltage Alternating Current Circuits § 75.900-4 Testing, examination, and...

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.

Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation

PubMed Central

Salavatian, Siamak; Beaumont, Eric; Longpré, Jean-Philippe; Armour, J. Andrew; Vinet, Alain; Jacquemet, Vincent; Shivkumar, Kalyanam

2016-01-01

Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 μs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P < 0.001). Convergent LCNs were preferentially activated by MNS. Preemptive RCV reduced MNS-induced changes in LCN activity (by 70%) while mitigating MNS-induced AF (by 75%). Preemptive LCV reduced LCN activity by 60% while mitigating AF potential by 40%. IC neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory. PMID:27591222

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.

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

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.

Electronic circuits

NASA Technical Reports Server (NTRS)

1976-01-01

Twenty-nine circuits and circuit techniques developed for communications and instrumentation technology are described. Topics include pulse-code modulation, phase-locked loops, data coding, data recording, detection circuits, logic circuits, oscillators, and amplifiers.

Encrypting Digital Camera with Automatic Encryption Key Deletion

NASA Technical Reports Server (NTRS)

Oakley, Ernest C. (Inventor)

2007-01-01

A digital video camera includes an image sensor capable of producing a frame of video data representing an image viewed by the sensor, an image memory for storing video data such as previously recorded frame data in a video frame location of the image memory, a read circuit for fetching the previously recorded frame data, an encryption circuit having an encryption key input connected to receive the previously recorded frame data from the read circuit as an encryption key, an un-encrypted data input connected to receive the frame of video data from the image sensor and an encrypted data output port, and a write circuit for writing a frame of encrypted video data received from the encrypted data output port of the encryption circuit to the memory and overwriting the video frame location storing the previously recorded frame data.

Chemistry integrated circuit: chemical system on a complementary metal oxide semiconductor integrated circuit.

PubMed

Nakazato, Kazuo

2014-03-28

By integrating chemical reactions on a large-scale integration (LSI) chip, new types of device can be created. For biomedical applications, monolithically integrated sensor arrays for potentiometric, amperometric and impedimetric sensing of biomolecules have been developed. The potentiometric sensor array detects pH and redox reaction as a statistical distribution of fluctuations in time and space. For the amperometric sensor array, a microelectrode structure for measuring multiple currents at high speed has been proposed. The impedimetric sensor array is designed to measure impedance up to 10 MHz. The multimodal sensor array will enable synthetic analysis and make it possible to standardize biosensor chips. Another approach is to create new functional devices by integrating molecular systems with LSI chips, for example image sensors that incorporate biological materials with a sensor array. The quantum yield of the photoelectric conversion of photosynthesis is 100%, which is extremely difficult to achieve by artificial means. In a recently developed process, a molecular wire is plugged directly into a biological photosynthetic system to efficiently conduct electrons to a gold electrode. A single photon can be detected at room temperature using such a system combined with a molecular single-electron transistor.

Development of a bench-top device for parallel climate-controlled recordings of neuronal cultures activity with microelectrode arrays.

PubMed

Regalia, Giulia; Biffi, Emilia; Achilli, Silvia; Ferrigno, Giancarlo; Menegon, Andrea; Pedrocchi, Alessandra

2016-02-01

Two binding requirements for in vitro studies on long-term neuronal networks dynamics are (i) finely controlled environmental conditions to keep neuronal cultures viable and provide reliable data for more than a few hours and (ii) parallel operation on multiple neuronal cultures to shorten experimental time scales and enhance data reproducibility. In order to fulfill these needs with a Microelectrode Arrays (MEA)-based system, we designed a stand-alone device that permits to uninterruptedly monitor neuronal cultures activity over long periods, overcoming drawbacks of existing MEA platforms. We integrated in a single device: (i) a closed chamber housing four MEAs equipped with access for chemical manipulations, (ii) environmental control systems and embedded sensors to reproduce and remotely monitor the standard in vitro culture environment on the lab bench (i.e. in terms of temperature, air CO2 and relative humidity), and (iii) a modular MEA interface analog front-end for reliable and parallel recordings. The system has been proven to assure environmental conditions stable, physiological and homogeneos across different cultures. Prolonged recordings (up to 10 days) of spontaneous and pharmacologically stimulated neuronal culture activity have not shown signs of rundown thanks to the environmental stability and have not required to withdraw the cells from the chamber for culture medium manipulations. This system represents an effective MEA-based solution to elucidate neuronal network phenomena with slow dynamics, such as long-term plasticity, effects of chronic pharmacological stimulations or late-onset pathological mechanisms. © 2015 Wiley Periodicals, Inc.

QSpike tools: a generic framework for parallel batch preprocessing of extracellular neuronal signals recorded by substrate microelectrode arrays

PubMed Central

Mahmud, Mufti; Pulizzi, Rocco; Vasilaki, Eleni; Giugliano, Michele

2014-01-01

Micro-Electrode Arrays (MEAs) have emerged as a mature technique to investigate brain (dys)functions in vivo and in in vitro animal models. Often referred to as “smart” Petri dishes, MEAs have demonstrated a great potential particularly for medium-throughput studies in vitro, both in academic and pharmaceutical industrial contexts. Enabling rapid comparison of ionic/pharmacological/genetic manipulations with control conditions, MEAs are employed to screen compounds by monitoring non-invasively the spontaneous and evoked neuronal electrical activity in longitudinal studies, with relatively inexpensive equipment. However, in order to acquire sufficient statistical significance, recordings last up to tens of minutes and generate large amount of raw data (e.g., 60 channels/MEA, 16 bits A/D conversion, 20 kHz sampling rate: approximately 8 GB/MEA,h uncompressed). Thus, when the experimental conditions to be tested are numerous, the availability of fast, standardized, and automated signal preprocessing becomes pivotal for any subsequent analysis and data archiving. To this aim, we developed an in-house cloud-computing system, named QSpike Tools, where CPU-intensive operations, required for preprocessing of each recorded channel (e.g., filtering, multi-unit activity detection, spike-sorting, etc.), are decomposed and batch-queued to a multi-core architecture or to a computers cluster. With the commercial availability of new and inexpensive high-density MEAs, we believe that disseminating QSpike Tools might facilitate its wide adoption and customization, and inspire the creation of community-supported cloud-computing facilities for MEAs users. PMID:24678297

Modeling and Simulation of Microelectrode-Retina Interactions

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

Beckerman, M

2002-11-30

The goal of the retinal prosthesis project is the development of an implantable microelectrode array that can be used to supply visually-driven electrical input to cells in the retina, bypassing nonfunctional rod and cone cells, thereby restoring vision to blind individuals. This goal will be achieved through the study of the fundamentals of electrical engineering, vision research, and biomedical engineering with the aim of acquiring the knowledge needed to engineer a high-density microelectrode-tissue hybrid sensor that will restore vision to millions of blind persons. The modeling and simulation task within this project is intended to address the question how bestmore » to stimulate, and communicate with, cells in the retina using implanted microelectrodes.« less

High-channel-count, high-density microelectrode array for closed-loop investigation of neuronal networks.

PubMed

Tsai, David; John, Esha; Chari, Tarun; Yuste, Rafael; Shepard, Kenneth

2015-01-01

We present a system for large-scale electrophysiological recording and stimulation of neural tissue with a planar topology. The recording system has 65,536 electrodes arranged in a 256 × 256 grid, with 25.5 μm pitch, and covering an area approximately 42.6 mm(2). The recording chain has 8.66 μV rms input-referred noise over a 100 ~ 10k Hz bandwidth while providing up to 66 dB of voltage gain. When recording from all electrodes in the array, it is capable of 10-kHz sampling per electrode. All electrodes can also perform patterned electrical microstimulation. The system produces ~ 1 GB/s of data when recording from the full array. To handle, store, and perform nearly real-time analyses of this large data stream, we developed a framework based around Xilinx FPGAs, Intel x86 CPUs and the NVIDIA Streaming Multiprocessors to interface with the electrode array.

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.

Advanced Ring-Shaped Microelectrode Assay Combined with Small Rectangular Electrode for Quasi-In vivo Measurement of Cell-to-Cell Conductance in Cardiomyocyte Network

NASA Astrophysics Data System (ADS)

Nomura, Fumimasa; Kaneko, Tomoyuki; Hamada, Tomoyo; Hattori, Akihiro; Yasuda, Kenji

2013-06-01

To predict the risk of fatal arrhythmia induced by cardiotoxicity in the highly complex human heart system, we have developed a novel quasi-in vivo electrophysiological measurement assay, which combines a ring-shaped human cardiomyocyte network and a set of two electrodes that form a large single ring-shaped electrode for the direct measurement of irregular cell-to-cell conductance occurrence in a cardiomyocyte network, and a small rectangular microelectrode for forced pacing of cardiomyocyte beating and for acquiring the field potential waveforms of cardiomyocytes. The advantages of this assay are as follows. The electrophysiological signals of cardiomyocytes in the ring-shaped network are superimposed directly on a single loop-shaped electrode, in which the information of asynchronous behavior of cell-to-cell conductance are included, without requiring a set of huge numbers of microelectrode arrays, a set of fast data conversion circuits, or a complex analysis in a computer. Another advantage is that the small rectangular electrode can control the position and timing of forced beating in a ring-shaped human induced pluripotent stem cell (hiPS)-derived cardiomyocyte network and can also acquire the field potentials of cardiomyocytes. First, we constructed the human iPS-derived cardiomyocyte ring-shaped network on the set of two electrodes, and acquired the field potential signals of particular cardiomyocytes in the ring-shaped cardiomyocyte network during simultaneous acquisition of the superimposed signals of whole-cardiomyocyte networks representing cell-to-cell conduction. Using the small rectangular electrode, we have also evaluated the response of the cell network to electrical stimulation. The mean and SD of the minimum stimulation voltage required for pacing (VMin) at the small rectangular electrode was 166+/-74 mV, which is the same as the magnitude of amplitude for the pacing using the ring-shaped electrode (179+/-33 mV). The results showed that the addition of a small rectangular electrode into the ring-shaped electrode was effective for the simultaneous measurement of whole-cell-network signals and single-cell/small-cluster signals on a local site in the cell network, and for the pacing by electrical stimulation of cardiomyocyte networks.

[Effects of bilateral deep brain stimulation in the subthalamic nucleus using two methods of target structure verification].

PubMed

Goubareva, N N; Fedorova, N V; Bril', E V; Tomskiy, A A; Gamaleya, A A; Poddubskaya, A A; Shabalov, V A; Omarova, S M

To evaluate the efficacy of deep brain stimulation in the subthalamic nucleus (DBS STN) in patients with Parkinson's disease (PD) using different methods of targeting according to the dynamics of motor symptoms of PD. The study involved 90 patients treated with DBS STN. In 30 cases intraoperative microelectrode recording (MER) was used. MER was not performed in 30 patients of the comparison group. The control group consisted of 30 patients with PD who received conservative treatment. Hoehn and Yahr scale, Tinetti Balance and Mobility Scale (TBMS), Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Quality of Life-39 Scoring System (РDQ-39), Schwab & England ADL Scale were used. Levodopa equivalent daily dose (LEDD, 2010) was calculated for each patient. The effect of DBS STN using intraoperative microelectrode recording on the main motor symptoms, motor complications, walking as well as indicators of quality of life and daily activities was shown. In both DBS STN groups, there was a significant reduction in the LEDD and marked improvement of the control of motor symptoms of PD. A significant reduction in the severity of motor fluctuations (50%) and drug-induced dyskinesia (51%) was observed. Quality of life and daily activity in off-medication condition were significantly improved in both DBS STN groups of patients, irrespective of the method of target planning (75-100%), compared with the control group.

Microelectrode array recordings of cultured hippocampal networks reveal a simple model for transcription and protein synthesis-dependent plasticity

PubMed Central

Arnold, Fiona JL; Hofmann, Frank; Bengtson, C. Peter; Wittmann, Malte; Vanhoutte, Peter; Bading, Hilmar

2005-01-01

A simplified cell culture system was developed to study neuronal plasticity. As changes in synaptic strength may alter network activity patterns, we grew hippocampal neurones on a microelectrode array (MEA) and monitored their collective behaviour with 60 electrodes simultaneously. We found that exposure of the network for 15 min to the GABAA receptor antagonist bicuculline induced an increase in synaptic efficacy at excitatory synapses that was associated with an increase in the frequency of miniature AMPA receptor-mediated EPSCs and a change in network activity from uncoordinated firing of neurones (lacking any recognizable pattern) to a highly organized, periodic and synchronous burst pattern. Induction of recurrent synchronous bursting was dependent on NMDA receptor activation and required extracellular signal-regulated kinase (ERK)1/2 signalling and translation of pre-existing mRNAs. Once induced, the burst pattern persisted for several days; its maintenance phase (> 4 h) was dependent on gene transcription taking place in a critical period of 120 min following induction. Thus, cultured hippocampal neurones display a simple, transcription and protein synthesis-dependent form of plasticity. The non-invasive nature of MEA recordings provides a significant advantage over traditional assays for synaptic connectivity (i.e. long-term potentiation in brain slices) and facilitates the search for activity-regulated genes critical for late-phase plasticity. PMID:15618268

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.

Microelectrode array recordings of cultured hippocampal networks reveal a simple model for transcription and protein synthesis-dependent plasticity.

PubMed

Arnold, Fiona J L; Hofmann, Frank; Bengtson, C Peter; Wittmann, Malte; Vanhoutte, Peter; Bading, Hilmar

2005-04-01

A simplified cell culture system was developed to study neuronal plasticity. As changes in synaptic strength may alter network activity patterns, we grew hippocampal neurones on a microelectrode array (MEA) and monitored their collective behaviour with 60 electrodes simultaneously. We found that exposure of the network for 15 min to the GABA(A) receptor antagonist bicuculline induced an increase in synaptic efficacy at excitatory synapses that was associated with an increase in the frequency of miniature AMPA receptor-mediated EPSCs and a change in network activity from uncoordinated firing of neurones (lacking any recognizable pattern) to a highly organized, periodic and synchronous burst pattern. Induction of recurrent synchronous bursting was dependent on NMDA receptor activation and required extracellular signal-regulated kinase (ERK)1/2 signalling and translation of pre-existing mRNAs. Once induced, the burst pattern persisted for several days; its maintenance phase (> 4 h) was dependent on gene transcription taking place in a critical period of 120 min following induction. Thus, cultured hippocampal neurones display a simple, transcription and protein synthesis-dependent form of plasticity. The non-invasive nature of MEA recordings provides a significant advantage over traditional assays for synaptic connectivity (i.e. long-term potentiation in brain slices) and facilitates the search for activity-regulated genes critical for late-phase plasticity.

Caudal Zona Incerta/VOP Radiofrequency Lesioning Guided by Combined Stereotactic MRI and Microelectrode Recording for Posttraumatic Midbrain Resting-Kinetic Tremor.

PubMed

Contreras Lopez, William Omar; Azevedo, Angelo R; Cury, Rubens G; Alencar, Francisco; Neville, Iuri S; Reis, Paul R; Navarro, Jessie; Monaco, Bernardo; da Silva, Fabio E Fernandes; Teixeira, Manoel J; Fonoff, Erich T

2016-02-01

Reporting the outcome of two patients who underwent unilateral ablative stereotactic surgery to treat pharmacologic resistant posttraumatic tremor (PTT). We present two patients (31 and 47 years old) with refractory PTT severely affecting their quality of life. Under stereotactic guidance, refined by T2-weighted magnetic resonance imaging and double-channel multiunit microelectrode recording (MER), three sequential radiofrequency lesions were performed in the caudal zona incerta (cZi) up to the base of thalamus (VOP). Effects of cZi/VOP lesion were prospectively rated with a tremor rating scale. Both patients demonstrated intraoperative tremor suppression with sustained results up to 18 months follow-up, with improvement of 92% and 84%, respectively, on the tremor rating scale. Tremor improvement was associated with enhancement functionality and quality of life for the patients. The patients returned to their work after the procedure. No adverse effects were observed up to the last follow-up. Radiofrequency lesion of the cZi/VOP target was effective for posttraumatic tremor in both cases. The use of T2-weighted images and MER was found helpful in increasing the precision and safety of the procedure, because it leads the RF probe by relying on neighbor structures based on thalamus and subthalamic nucleus. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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

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.

Functional characterization of GABAA receptor-mediated modulation of cortical neuron network activity in microelectrode array recordings.

PubMed

Bader, Benjamin M; Steder, Anne; Klein, Anders Bue; Frølund, Bente; Schroeder, Olaf H U; Jensen, Anders A

2017-01-01

The numerous γ-aminobutyric acid type A receptor (GABAAR) subtypes are differentially expressed and mediate distinct functions at neuronal level. In this study we have investigated GABAAR-mediated modulation of the spontaneous activity patterns of primary neuronal networks from murine frontal cortex by characterizing the effects induced by a wide selection of pharmacological tools at a plethora of activity parameters in microelectrode array (MEA) recordings. The basic characteristics of the primary cortical neurons used in the recordings were studied in some detail, and the expression levels of various GABAAR subunits were investigated by western blotting and RT-qPCR. In the MEA recordings, the pan-GABAAR agonist muscimol and the GABABR agonist baclofen were observed to mediate phenotypically distinct changes in cortical network activity. Selective augmentation of αβγ GABAAR signaling by diazepam and of δ-containing GABAAR (δ-GABAAR) signaling by DS1 produced pronounced changes in the majority of the activity parameters, both drugs mediating similar patterns of activity changes as muscimol. The apparent importance of δ-GABAAR signaling for network activity was largely corroborated by the effects induced by the functionally selective δ-GABAAR agonists THIP and Thio-THIP, whereas the δ-GABAAR selective potentiator DS2 only mediated modest effects on network activity, even when co-applied with low THIP concentrations. Interestingly, diazepam exhibited dramatically right-shifted concentration-response relationships at many of the activity parameters when co-applied with a trace concentration of DS1 compared to when applied alone. In contrast, the potencies and efficacies displayed by DS1 at the networks were not substantially altered by the concomitant presence of diazepam. In conclusion, the holistic nature of the information extractable from the MEA recordings offers interesting insights into the contributions of various GABAAR subtypes/subgroups to cortical network activity and the putative functional interplay between these receptors in these neurons.

Relationship between physiological excitatory and inhibitory measures of excitability in the left vs. right human motor cortex and peripheral electrodermal activity.

PubMed

Bracco, Martina; Turriziani, Patrizia; Smirni, Daniela; Mangano, Renata Giuseppa; Oliveri, Massimiliano

2017-02-22

The current study was aimed at investigating the relationships of excitatory and inhibitory circuits of the left vs. right primary motor cortex with peripheral electrodermal activity (EDA). Ten healthy subjects participated in two experimental sessions. In each session, EDA was recorded for 10min from the palmar surface of the left hand. Immediately after EDA recording, Transcranial Magnetic Stimulation (TMS) was used to probe excitatory and inhibitory circuits of the left or right primary motor cortex using two protocols of stimulation: the input-output curve for recording of motor evoked potentials, for testing excitatory circuits; the long-interval cortical inhibition (LICI) protocol, for testing inhibitory circuits. In both cases, motor evoked potentials were recorded with surface electrodes from a contralateral hand muscle. The main results showed that in the right motor cortex, excitatory circuits directly correlate and inhibitory circuits inversely correlate with sympathetic activation. In the left motor cortex, both excitatory and inhibitory circuits are inversely correlated with sympathetic activation. These findings may suggest a bi-hemispheric mode of control of vegetative system by motor cortices, with the right hemisphere mainly involved in sympathetic control. Copyright © 2017. Published by Elsevier B.V.

Heterogeneous Origins of Human Sleep Spindles in Different Cortical Layers.

PubMed

Hagler, Donald J; Ulbert, István; Wittner, Lucia; Erőss, Loránd; Madsen, Joseph R; Devinsky, Orrin; Doyle, Werner; Fabó, Dániel; Cash, Sydney S; Halgren, Eric

2018-03-21

Sleep spindles are a cardinal feature in human NREM sleep and may be important for memory consolidation. We studied the intracortical organization of spindles in men and women by recording spontaneous sleep spindles from different cortical layers using linear microelectrode arrays. Two patterns of spindle generation were identified using visual inspection, and confirmed with factor analysis. Spindles (10-16 Hz) were largest and most common in upper and middle channels, with limited involvement of deep channels. Many spindles were observed in only upper or only middle channels, but approximately half occurred in both. In spindles involving both middle and upper channels, the spindle envelope onset in middle channels led upper by ∼25-50 ms on average. The phase relationship between spindle waves in upper and middle channels varied dynamically within spindle epochs, and across individuals. Current source density analysis demonstrated that upper and middle channel spindles were both generated by an excitatory supragranular current sink while an additional deep source was present for middle channel spindles only. Only middle channel spindles were accompanied by deep low (25-50 Hz) and high (70-170 Hz) gamma activity. These results suggest that upper channel spindles are generated by supragranular pyramids, and middle channel by infragranular. Possibly, middle channel spindles are generated by core thalamocortical afferents, and upper channel by matrix. The concurrence of these patterns could reflect engagement of cortical circuits in the integration of more focal (core) and distributed (matrix) aspects of memory. These results demonstrate that at least two distinct intracortical systems generate human sleep spindles. SIGNIFICANCE STATEMENT Bursts of ∼14 Hz oscillations, lasting ∼1 s, have been recognized for over 80 years as cardinal features of mammalian sleep. Recent findings suggest that they play a key role in organizing cortical activity during memory consolidation. We used linear microelectrode arrays to study their intracortical organization in humans. We found that spindles could be divided into two types. One mainly engages upper layers of the cortex, which are considered to be specialized for associative activity. The other engages both upper and middle layers, including those devoted to sensory input. The interaction of these two spindle types may help organize the interaction of sensory and associative aspects of memory consolidation. Copyright © 2018 the authors 0270-6474/18/383013-13$15.00/0.

Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor.

PubMed

Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M

2011-12-18

The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be recorded, thus showing that a stable and tight seal forms between the nanotube and cell membrane. We also show that multiple BIT-FETs can record multiplexed intracellular signals from both single cells and networks of cells.

Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor

NASA Astrophysics Data System (ADS)

Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M.

2012-03-01

The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be recorded, thus showing that a stable and tight seal forms between the nanotube and cell membrane. We also show that multiple BIT-FETs can record multiplexed intracellular signals from both single cells and networks of cells.

Large-scale, high-density (up to 512 channels) recording of local circuits in behaving animals

PubMed Central

Berényi, Antal; Somogyvári, Zoltán; Nagy, Anett J.; Roux, Lisa; Long, John D.; Fujisawa, Shigeyoshi; Stark, Eran; Leonardo, Anthony; Harris, Timothy D.

2013-01-01

Monitoring representative fractions of neurons from multiple brain circuits in behaving animals is necessary for understanding neuronal computation. Here, we describe a system that allows high-channel-count recordings from a small volume of neuronal tissue using a lightweight signal multiplexing headstage that permits free behavior of small rodents. The system integrates multishank, high-density recording silicon probes, ultraflexible interconnects, and a miniaturized microdrive. These improvements allowed for simultaneous recordings of local field potentials and unit activity from hundreds of sites without confining free movements of the animal. The advantages of large-scale recordings are illustrated by determining the electroanatomic boundaries of layers and regions in the hippocampus and neocortex and constructing a circuit diagram of functional connections among neurons in real anatomic space. These methods will allow the investigation of circuit operations and behavior-dependent interregional interactions for testing hypotheses of neural networks and brain function. PMID:24353300

Spatial Analysis of Slowly Oscillating Electric Activity in the Gut of Mice Using Low Impedance Arrayed Microelectrodes

PubMed Central

Taniguchi, Mizuki; Kajioka, Shunichi; Shozib, Habibul B.; Sawamura, Kenta; Nakayama, Shinsuke

2013-01-01

Smooth and elaborate gut motility is based on cellular cooperation, including smooth muscle, enteric neurons and special interstitial cells acting as pacemaker cells. Therefore, spatial characterization of electric activity in tissues containing these electric excitable cells is required for a precise understanding of gut motility. Furthermore, tools to evaluate spatial electric activity in a small area would be useful for the investigation of model animals. We thus employed a microelectrode array (MEA) system to simultaneously measure a set of 8×8 field potentials in a square area of ∼1 mm2. The size of each recording electrode was 50×50 µm2, however the surface area was increased by fixing platinum black particles. The impedance of microelectrode was sufficiently low to apply a high-pass filter of 0.1 Hz. Mapping of spectral power, and auto-correlation and cross-correlation parameters characterized the spatial properties of spontaneous electric activity in the ileum of wild-type (WT) and W/Wv mice, the latter serving as a model of impaired network of pacemaking interstitial cells. Namely, electric activities measured varied in both size and cooperativity in W/Wv mice, despite the small area. In the ileum of WT mice, procedures suppressing the excitability of smooth muscle and neurons altered the propagation of spontaneous electric activity, but had little change in the period of oscillations. In conclusion, MEA with low impedance electrodes enables to measure slowly oscillating electric activity, and is useful to evaluate both histological and functional changes in the spatio-temporal property of gut electric activity. PMID:24124480

ZERO SUPPRESSION FOR RECORDERS

DOEpatents

Fort, W.G.S.

1958-12-30

A zero-suppression circuit for self-balancing recorder instruments is presented. The essential elements of the circuit include a converter-amplifier having two inputs, one for a reference voltage and the other for the signal voltage under analysis, and a servomotor with two control windings, one coupled to the a-c output of the converter-amplifier and the other receiving a reference input. Each input circuit to the converter-amplifier has a variable potentiometer and the sliders of the potentiometer are ganged together for movement by the servoinotor. The particular noveity of the circuit resides in the selection of resistance values for the potentiometer and a resistor in series with the potentiometer of the signal circuit to ensure the full value of signal voltage variation is impressed on a recorder mechanism driven by servomotor.

A Wireless FSCV Monitoring IC With Analog Background Subtraction and UWB Telemetry.

PubMed

Dorta-Quiñones, Carlos I; Wang, Xiao Y; Dokania, Rajeev K; Gailey, Alycia; Lindau, Manfred; Apsel, Alyssa B

2016-04-01

A 30-μW wireless fast-scan cyclic voltammetry monitoring integrated circuit for ultra-wideband (UWB) transmission of dopamine release events in freely-behaving small animals is presented. On-chip integration of analog background subtraction and UWB telemetry yields a 32-fold increase in resolution versus standard Nyquist-rate conversion alone, near a four-fold decrease in the volume of uplink data versus single-bit, third-order, delta-sigma modulation, and more than a 20-fold reduction in transmit power versus narrowband transmission for low data rates. The 1.5- mm(2) chip, which was fabricated in 65-nm CMOS technology, consists of a low-noise potentiostat frontend, a two-step analog-to-digital converter (ADC), and an impulse-radio UWB transmitter (TX). The duty-cycled frontend and ADC/UWB-TX blocks draw 4 μA and 15 μA from 3-V and 1.2-V supplies, respectively. The chip achieves an input-referred current noise of 92 pA(rms) and an input current range of ±430 nA at a conversion rate of 10 kHz. The packaged device operates from a 3-V coin-cell battery, measures 4.7 × 1.9 cm(2), weighs 4.3 g (including the battery and antenna), and can be carried by small animals. The system was validated by wirelessly recording flow-injection of dopamine with concentrations in the range of 250 nM to 1 μM with a carbon-fiber microelectrode (CFM) using 300-V/s FSCV.

A Wireless FSCV Monitoring IC with Analog Background Subtraction and UWB Telemetry

PubMed Central

Dorta-Quiñones, Carlos I.; Wang, Xiao Y.; Dokania, Rajeev K.; Gailey, Alycia; Lindau, Manfred; Apsel, Alyssa B.

2015-01-01

A 30-μW wireless fast-scan cyclic voltammetry monitoring integrated circuit for ultra-wideband (UWB) transmission of dopamine release events in freely-behaving small animals is presented. On-chip integration of analog background subtraction and UWB telemetry yields a 32-fold increase in resolution versus standard Nyquist-rate conversion alone, near a four-fold decrease in the volume of uplink data versus single-bit, third-order, delta-sigma modulation, and more than a 20-fold reduction in transmit power versus narrowband transmission for low data rates. The 1.5-mm2 chip, which was fabricated in 65-nm CMOS technology, consists of a low-noise potentiostat frontend, a two-step analog-to-digital converter (ADC), and an impulse-radio UWB transmitter (TX). The duty-cycled frontend and ADC/UWB-TX blocks draw 4 μA and 15 μA from 3-V and 1.2-V supplies, respectively. The chip achieves an input-referred current noise of 92 pArms and an input current range of ±430 nA at a conversion rate of 10 kHz. The packaged device operates from a 3-V coin-cell battery, measures 4.7 × 1.9 cm2, weighs 4.3 g (including the battery and antenna), and can be carried by small animals. The system was validated by wirelessly recording flow-injection of dopamine with concentrations in the range of 250 nM to 1 μM with a carbon-fiber microelectrode (CFM) using 300-V/s FSCV. PMID:26057983

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.

Isolated Rat Hepatocyte Couplets: A Primary Secretory Unit for Electrophysiologic Studies of Bile Secretory Function

NASA Astrophysics Data System (ADS)

Graf, J.; Gautam, A.; Boyer, J. L.

1984-10-01

Hepatocyte couplets were isolated by collagenase perfusion from rat liver. Between adjacent cells, the bile canaliculus forma a closed space into which secretion occurs. As in intact liver, Mg2+-ATPase is localized at the canalicular lumen, the organic anion fluorescein is excreted, and secretion is modified by osmotic gradients. By passing a microelectrode through one cell into the canalicular vacuole, a transepithelial potential profile was obtained. In 27 cell couplets the steady-state intracellular (-26.3 ± 5.3 mV) and intracanalicular (-5.9 ± 3.3 mV) potentials were recorded at 37 degrees C with reference to the external medium. Input resistances were determined within the cell (86 ± 23 MΩ ) and in the bile canalicular lumen (32 ± 17 MΩ ) by passing current pulses through the microelectrode. These data define electrical driving forces for ion transport across the sinusoidal, canalicular, and paracellular barriers and indicate ion permeation across a leaky paracellular junctional pathway. These findings indicate that the isolated hepatocyte couplet is an effective model for electrophysiologic studies of bile secretory function.

Modulation of cultured neural networks using neurotrophin release from hydrogel-coated microelectrode arrays

NASA Astrophysics Data System (ADS)

Jun, Sang Beom; Hynd, Matthew R.; Dowell-Mesfin, Natalie M.; Al-Kofahi, Yousef; Roysam, Badrinath; Shain, William; Kim, Sung June

2008-06-01

Polyacrylamide and poly(ethylene glycol) diacrylate hydrogels were synthesized and characterized for use as drug release and substrates for neuron cell culture. Protein release kinetics was determined by incorporating bovine serum albumin (BSA) into hydrogels during polymerization. To determine if hydrogel incorporation and release affect bioactivity, alkaline phosphatase was incorporated into hydrogels and a released enzyme activity determined using the fluorescence-based ELF-97 assay. Hydrogels were then used to deliver a brain-derived neurotrophic factor (BDNF) from hydrogels polymerized over planar microelectrode arrays (MEAs). Primary hippocampal neurons were cultured on both control and neurotrophin-containing hydrogel-coated MEAs. The effect of released BDNF on neurite length and process arborization was investigated using automated image analysis. An increased spontaneous activity as a response to the released BDNF was recorded from the neurons cultured on the top of hydrogel layers. These results demonstrate that proteins of biological interest can be incorporated into hydrogels to modulate development and function of cultured neural networks. These results also set the stage for development of hydrogel-coated neural prosthetic devices for local delivery of various biologically active molecules.

A microelectrode array electrodeposited with reduced graphene oxide and Pt nanoparticles for norepinephrine and electrophysiological recordings

NASA Astrophysics Data System (ADS)

Wang, Li; Song, Yilin; Zhang, Yu; Xu, Shengwei; Xu, Huiren; Wang, Mixia; Wang, Yang; Cai, Xinxia

2017-11-01

Norepinephrine (NE), a common neurotransmitter released by locus coeruleus neurons, plays an essential role in the communication mechanism of the mammalian nervous system. In this work, a microelectrode array (MEA) was fabricated by micro-electromechanical system (MEMS) technology to provide a rapid, sensitive and reliable method for the direct determination in NE dynamic secretion. To improve the electrical performance, the MEA was electrodeposited with the reduced graphene oxide and Pt nanoparticles (rGOPNps). rGOPNps-MEA was investigated using scanning electron microscopy, atomic force microscopy and electrochemical impedance spectroscopy, differential pulse voltammetry exhibited remarkably electrocatalytic properties towards NE. Calibration results showed a sensitivity of 1.03 nA µM-1 to NE with a detection limit of 0.08 µM. In Particular, the MEA was successfully used for measuring dynamic extracellular NE secretion from the locus coeruleus brain slice, as well as monitoring spike firing from the hippocampal brain slice. This fabricated device has potential in studies of spatially resolved delivery of trace neurochemicals and electrophysiological activities of a variety of biological tissues in vitro.

Implantation of Neural Probes in the Brain Elicits Oxidative Stress

PubMed Central

Ereifej, Evon S.; Rial, Griffin M.; Hermann, John K.; Smith, Cara S.; Meade, Seth M.; Rayyan, Jacob M.; Chen, Keying; Feng, He; Capadona, Jeffrey R.

2018-01-01

Clinical implantation of intracortical microelectrodes has been hindered, at least in part, by the perpetual inflammatory response occurring after device implantation. The neuroinflammatory response observed after device implantation has been correlated to oxidative stress that occurs due to neurological injury and disease. However, there has yet to be a definitive link of oxidative stress to intracortical microelectrode implantation. Thus, the objective of this study is to give direct evidence of oxidative stress following intracortical microelectrode implantation. This study also aims to identify potential molecular targets to attenuate oxidative stress observed postimplantation. Here, we implanted adult rats with silicon non-functional microelectrode probes for 4 weeks and compared the oxidative stress response to no surgery controls through postmortem gene expression analysis and qualitative histological observation of oxidative stress markers. Gene expression analysis results at 4 weeks postimplantation indicated that EH domain-containing 2, prion protein gene (Prnp), and Stearoyl-Coenzyme A desaturase 1 (Scd1) were all significantly higher for animals implanted with intracortical microelectrode probes compared to no surgery control animals. To the contrary, NADPH oxidase activator 1 (Noxa1) relative gene expression was significantly lower for implanted animals compared to no surgery control animals. Histological observation of oxidative stress showed an increased expression of oxidized proteins, lipids, and nucleic acids concentrated around the implant site. Collectively, our results reveal there is a presence of oxidative stress following intracortical microelectrode implantation compared to no surgery controls. Further investigation targeting these specific oxidative stress linked genes could be beneficial to understanding potential mechanisms and downstream therapeutics that can be utilized to reduce oxidative stress-mediated damage following microelectrode implantation. PMID:29487848

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

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

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.

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.

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.

Chronic recruitment of primary afferent neurons by microstimulation in the feline dorsal root ganglia

NASA Astrophysics Data System (ADS)

Fisher, Lee E.; Ayers, Christopher A.; Ciollaro, Mattia; Ventura, Valérie; Weber, Douglas J.; Gaunt, Robert A.

2014-06-01

Objective. This study describes results of primary afferent neural microstimulation experiments using microelectrode arrays implanted chronically in the lumbar dorsal root ganglia (DRG) of four cats. The goal was to test the stability and selectivity of these microelectrode arrays as a potential interface for restoration of somatosensory feedback after damage to the nervous system such as amputation. Approach. A five-contact nerve-cuff electrode implanted on the sciatic nerve was used to record the antidromic compound action potential response to DRG microstimulation (2-15 µA biphasic pulses, 200 µs cathodal pulse width), and the threshold for eliciting a response was tracked over time. Recorded responses were segregated based on conduction velocity to determine thresholds for recruiting Group I and Group II/Aβ primary afferent fibers. Main results. Thresholds were initially low (5.1 ± 2.3 µA for Group I and 6.3 ± 2.0 µA for Group II/Aβ) and increased over time. Additionally the number of electrodes with thresholds less than or equal to 15 µA decreased over time. Approximately 12% of tested electrodes continued to elicit responses at 15 µA up to 26 weeks after implantation. Higher stimulation intensities (up to 30 µA) were tested in one cat at 23 weeks post-implantation yielding responses on over 20 additional electrodes. Within the first six weeks after implantation, approximately equal numbers of electrodes elicited only Group I or Group II/Aβ responses at threshold, but the relative proportion of Group II/Aβ responses decreased over time. Significance. These results suggest that it is possible to activate Group I or Group II/Aβ primary afferent fibers in isolation with penetrating microelectrode arrays implanted in the DRG, and that those responses can be elicited up to 26 weeks after implantation, although it may be difficult to achieve a consistent response day-to-day with currently available electrode technology. The DRG are compelling targets for sensory neuroprostheses with potential to achieve recruitment of a range of sensory fiber types over multiple months after implantation.

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

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.

Telemetric recordings of single neuron activity and visual scenes in monkeys walking in an open field.

PubMed

Lei, Yanlin; Sun, Ninglei; Wilson, Fraser A W; Wang, Xiusong; Chen, Nanhui; Yang, Jianzhen; Peng, Yanping; Wang, Jianhong; Tian, Shaohua; Wang, Maohua; Miao, Yingda; Zhu, Weina; Qi, Hua; Ma, Yuanye

2004-05-30

This paper describes a portable recording system and methods for obtaining chronic recordings of single units and tracking rhesus monkey behavior in an open field. The integrated system consists of four major components: (1) microelectrode assembly; (2) head-stage; (3) recording station; and (4) data storage station, the first three of which are carried by the monkey and weigh 800 g. Our system provides synchronized video and electrophysiological signals, which are transmitted by a wireless system to a distance of 50 m. Its major advantages are that neuronal recordings are made in freely moving monkeys, and well-separated action potentials with amplitude five times higher than the background noise are usually recorded and readily kept for many hours. Using this system, we were able to study "place cells" in non-human primate brains. The described methods provide a new way to examine correlations between single neuron activity and primate behaviors, and can also be used to study the cellular basis of social behaviors in non-human primates.

Development and investigation of flexible polymer neural probe for chronic neural recording

NASA Astrophysics Data System (ADS)

Smith, Courtney; Song, Kyo D.; Yoon, Hargsoon; Kim, Woong-Ki; Zeng, Tao; Sanford, Larry D.

2012-04-01

Neural recording through microelectrodes requires biocompatibility and long term chronic usage. With a potential for various applications and effort to improve the performance of neural recording probes, consideration is taken to the tissue and cellular effects in these device designs. The degeneration of neurons due to brain tissue motion is an issue along with brain tissue inflammation in the insertion of the probes. To account for motion and irritation the material structure of the probes must be improved upon. This research presents the fabrication of neural probes on the microscale utilizing flexible polymers. Polyimide neural probes have been considered possibly to reduce degradation in their variability caused by brain motion. The microfabrication of the polyimide neural probe has an increased flexibility while accounting for biocompatibility and the needs for chronic use. Through microfabrication processes a needle probe is produced and tested for neural recording.

Formation of holographic memory for optically reconfigurable gate array by angle-multiplexing recording of multi-circuit information in liquid crystal composites

NASA Astrophysics Data System (ADS)

Ogiwara, Akifumi; Maekawa, Hikaru; Watanabe, Minoru; Moriwaki, Retsu

2014-02-01

A holographic polymer-dispersed liquid crystal (HPDLC) memory to record multi-context information for an optically reconfigurable gate array is formed by the angle-multiplexing recording using a successive laser exposure in liquid crystal (LC) composites. The laser illumination system is constructed using the half mirror and photomask written by the different configuration contexts placed on the motorized stages under the control of a personal computer. The fabricated holographic memory implements a precise reconstruction of configuration contexts corresponding to the various logical circuits such as OR circuit and NOR circuit by the laser illumination at different incident angle in the HPDLC memory.

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 evaluation of the conductivity profile in the somatosensory barrel cortex of Wistar rats.

PubMed

Goto, Takakuni; Hatanaka, Rieko; Ogawa, Takeshi; Sumiyoshi, Akira; Riera, Jorge; Kawashima, Ryuta

2010-12-01

Microelectrode arrays used to record local field potentials from the brain are being built with increasingly more spatial resolution, ranging from the initially developed laminar arrays to those with planar and three-dimensional (3D) formats. In parallel with such development in recording techniques, current source density (CSD) analyses have recently been expanded up to the continuous-3D form. Unfortunately, the effect of the conductivity profile on the CSD analysis performed with contemporary microelectrode arrays has not yet been evaluated and most of the studies assumed it was homogeneous and isotropic. In this study, we measured the conductivity profile in the somatosensory barrel cortex of Wistar rats. To that end, we combined multisite electrophysiological data recorded with a homemade assembly of silicon-based probes and a nonlinear least-squares algorithm that implicitly assumed that the cerebral cortex of rodents could be locally approximated as a layered anisotropic spherical volume conductor. The eccentricity of the six cortical layers in the somatosensory barrel cortex was evaluated from postmortem histological images. We provided evidence for the local spherical character of the entire barrels field, with concentric cortical layers. We found significant laminar dependencies in the conductivity values with radial/tangential anisotropies. These results were in agreement with the layer-dependent orientations of myelinated axons, but hardly related to densities of cells. Finally, we demonstrated through simulations that ignoring the real conductivity profile in the somatosensory barrel cortex of rats caused considerable errors in the CSD reconstruction, with pronounced effects on the continuous-3D form and charge-unbalanced CSD. We concluded that the conductivity profile must be included in future developments of CSD analysis, especially for rodents.

Multivariate regression methods for estimating velocity of ictal discharges from human microelectrode recordings

NASA Astrophysics Data System (ADS)

Liou, Jyun-you; Smith, Elliot H.; Bateman, Lisa M.; McKhann, Guy M., II; Goodman, Robert R.; Greger, Bradley; Davis, Tyler S.; Kellis, Spencer S.; House, Paul A.; Schevon, Catherine A.

2017-08-01

Objective. Epileptiform discharges, an electrophysiological hallmark of seizures, can propagate across cortical tissue in a manner similar to traveling waves. Recent work has focused attention on the origination and propagation patterns of these discharges, yielding important clues to their source location and mechanism of travel. However, systematic studies of methods for measuring propagation are lacking. Approach. We analyzed epileptiform discharges in microelectrode array recordings of human seizures. The array records multiunit activity and local field potentials at 400 micron spatial resolution, from a small cortical site free of obstructions. We evaluated several computationally efficient statistical methods for calculating traveling wave velocity, benchmarking them to analyses of associated neuronal burst firing. Main results. Over 90% of discharges met statistical criteria for propagation across the sampled cortical territory. Detection rate, direction and speed estimates derived from a multiunit estimator were compared to four field potential-based estimators: negative peak, maximum descent, high gamma power, and cross-correlation. Interestingly, the methods that were computationally simplest and most efficient (negative peak and maximal descent) offer non-inferior results in predicting neuronal traveling wave velocities compared to the other two, more complex methods. Moreover, the negative peak and maximal descent methods proved to be more robust against reduced spatial sampling challenges. Using least absolute deviation in place of least squares error minimized the impact of outliers, and reduced the discrepancies between local field potential-based and multiunit estimators. Significance. Our findings suggest that ictal epileptiform discharges typically take the form of exceptionally strong, rapidly traveling waves, with propagation detectable across millimeter distances. The sequential activation of neurons in space can be inferred from clinically-observable EEG data, with a variety of straightforward computation methods available. This opens possibilities for systematic assessments of ictal discharge propagation in clinical and research settings.

30 CFR 75.800-4 - Testing, examination, and maintenance of circuit breakers; record.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Underground High-Voltage Distribution § 75.800-4 Testing, examination, and maintenance of circuit breakers... adjustment of all circuit breakers protecting high-voltage circuits which enter any underground area of the...

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.

Simple and fast method for fabrication of endoscopic implantable sensor arrays.

PubMed

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

2014-06-26

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.

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

Theta-burst microstimulation in the human entorhinal area improves memory specificity.

PubMed

Titiz, Ali S; Hill, Michael R H; Mankin, Emily A; M Aghajan, Zahra; Eliashiv, Dawn; Tchemodanov, Natalia; Maoz, Uri; Stern, John; Tran, Michelle E; Schuette, Peter; Behnke, Eric; Suthana, Nanthia A; Fried, Itzhak

2017-10-24

The hippocampus is critical for episodic memory, and synaptic changes induced by long-term potentiation (LTP) are thought to underlie memory formation. In rodents, hippocampal LTP may be induced through electrical stimulation of the perforant path. To test whether similar techniques could improve episodic memory in humans, we implemented a microstimulation technique that allowed delivery of low-current electrical stimulation via 100 μm -diameter microelectrodes. As thirteen neurosurgical patients performed a person recognition task, microstimulation was applied in a theta-burst pattern, shown to optimally induce LTP. Microstimulation in the right entorhinal area during learning significantly improved subsequent memory specificity for novel portraits; participants were able both to recognize previously-viewed photos and reject similar lures. These results suggest that microstimulation with physiologic level currents-a radical departure from commonly used deep brain stimulation protocols-is sufficient to modulate human behavior and provides an avenue for refined interrogation of the circuits involved in human memory.

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.

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 ...

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.

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

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

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.

The Plastic Response to Monocular Deprivation Persists after Chronic Depletion of Norepinephrine in Kitten Visual Cortex.

DTIC Science & Technology

1982-06-21

82 N F BEAR, J 0 DANIELS NOOOI%-& B -K-0136 UNCLASSIFIED TR-3 NL 0 M I~i Sol~hhh~hI ffl join hh So ’ g . I3 *22 Q36m 111112=" MICROCOPY RESOLUTION TEST...CHART NATIONAL BUREAU OF STANDARDS_-1963-A SECURITY CLASSIFICATION OF THIS PAGE ( b *ie., D.,. Entiered) REPORT DOCUMENTATION PAGE 4 RV.ADWSTRUCTIONS...microelectrodes ( Levick , 1972) were fitted into our dual microdrive advance which allows stimultaneous recording from both hemispheres. Each electrode was

Effects of L-glutamate on 1F Helix aspersa neurons

NASA Astrophysics Data System (ADS)

Bernal-Martínez, Juan; Ortega Soto, Arturo

2004-09-01

The aim of this work is to characterize the effect of L-glut and related compounds on the electrical properties of 1F identified neurons of the garden snail Helix aspersa. We used intracellular recording experiments with regular microelectrodes, in current clamp conditions. We report here that the putative L-glut receptor present in 1F Helix neurons has some similarities with the L-glut receptor present in vertebrates, regarding ionic permeability and biophysical properties. However, these responses show different pharmacological properties from those receptors found in vertebrates and mammals.

Development of the Mayo Investigational Neuromodulation Control System: toward a closed-loop electrochemical feedback system for deep brain stimulation

PubMed Central

Chang, Su-Youne; Kimble, Christopher J.; Kim, Inyong; Paek, Seungleal B.; Kressin, Kenneth R.; Boesche, Joshua B.; Whitlock, Sidney V.; Eaker, Diane R.; Kasasbeh, Aimen; Horne, April E.; Blaha, Charles D.; Bennet, Kevin E.; Lee, Kendall H.

2014-01-01

Object Conventional deep brain stimulation (DBS) devices continue to rely on an open-loop system in which stimulation is independent of functional neural feedback. The authors previously proposed that as the foundation of a DBS “smart” device, a closed-loop system based on neurochemical feedback, may have the potential to improve therapeutic outcomes. Alterations in neurochemical release are thought to be linked to the clinical benefit of DBS, and fast-scan cyclic voltammetry (FSCV) has been shown to be effective for recording these evoked neurochemical changes. However, the combination of FSCV with conventional DBS devices interferes with the recording and identification of the evoked analytes. To integrate neurochemical recording with neurostimulation, the authors developed the Mayo Investigational Neuromodulation Control System (MINCS), a novel, wirelessly controlled stimulation device designed to interface with FSCV performed by their previously described Wireless Instantaneous Neurochemical Concentration Sensing System (WINCS). Methods To test the functionality of these integrated devices, various frequencies of electrical stimulation were applied by MINCS to the medial forebrain bundle of the anesthetized rat, and striatal dopamine release was recorded by WINCS. The parameters for FSCV in the present study consisted of a pyramidal voltage waveform applied to the carbon-fiber microelectrode every 100 msec, ramping between −0.4 V and +1.5 V with respect to an Ag/AgCl reference electrode at a scan rate of either 400 V/sec or 1000 V/sec. The carbon-fiber microelectrode was held at the baseline potential of −0.4 V between scans. Results By using MINCS in conjunction with WINCS coordinated through an optic fiber, the authors interleaved intervals of electrical stimulation with FSCV scans and thus obtained artifact-free wireless FSCV recordings. Electrical stimulation of the medial forebrain bundle in the anesthetized rat by MINCS elicited striatal dopamine release that was time-locked to stimulation and increased progressively with stimulation frequency. Conclusions Here, the authors report a series of proof-of-principle tests in the rat brain demonstrating MINCS to be a reliable and flexible stimulation device that, when used in conjunction with WINCS, performs wirelessly controlled stimulation concurrent with artifact-free neurochemical recording. These findings suggest that the integration of neurochemical recording with neurostimulation may be a useful first step toward the development of a closed-loop DBS system for human application. PMID:24116724

Sensor readout detector circuit

DOEpatents

Chu, Dahlon D.; Thelen, Jr., Donald C.

1998-01-01

A sensor readout detector circuit is disclosed that is capable of detecting sensor signals down to a few nanoamperes or less in a high (microampere) background noise level. The circuit operates at a very low standby power level and is triggerable by a sensor event signal that is above a predetermined threshold level. A plurality of sensor readout detector circuits can be formed on a substrate as an integrated circuit (IC). These circuits can operate to process data from an array of sensors in parallel, with only data from active sensors being processed for digitization and analysis. This allows the IC to operate at a low power level with a high data throughput for the active sensors. The circuit may be used with many different types of sensors, including photodetectors, capacitance sensors, chemically-sensitive sensors or combinations thereof to provide a capability for recording transient events or for recording data for a predetermined period of time following an event trigger. The sensor readout detector circuit has applications for portable or satellite-based sensor systems.

Sensor readout detector circuit

DOEpatents

Chu, D.D.; Thelen, D.C. Jr.

1998-08-11

A sensor readout detector circuit is disclosed that is capable of detecting sensor signals down to a few nanoamperes or less in a high (microampere) background noise level. The circuit operates at a very low standby power level and is triggerable by a sensor event signal that is above a predetermined threshold level. A plurality of sensor readout detector circuits can be formed on a substrate as an integrated circuit (IC). These circuits can operate to process data from an array of sensors in parallel, with only data from active sensors being processed for digitization and analysis. This allows the IC to operate at a low power level with a high data throughput for the active sensors. The circuit may be used with many different types of sensors, including photodetectors, capacitance sensors, chemically-sensitive sensors or combinations thereof to provide a capability for recording transient events or for recording data for a predetermined period of time following an event trigger. The sensor readout detector circuit has applications for portable or satellite-based sensor systems. 6 figs.

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.

Bioelectronic tongue of taste buds on microelectrode array for salt sensing.

PubMed

Liu, Qingjun; Zhang, Fenni; Zhang, Diming; Hu, Ning; Wang, Hua; Hsia, K Jimmy; Wang, Ping

2013-02-15

Taste has received great attention for its potential applications. In this work, we combine the biological tissue with micro-chips to establish a novel bioelectronic tongue system for salt taste detection. Before experiment, we established a computational model of action potential in salt taste receptor cell, simulating the responsive results to natural salt stimuli of NaCl solution with various concentrations. Then 36-channel microelectrode arrays (MEA) with the diameter of 30 μm were fabricated on the glass substrate, and taste epithelium was stripped from rat and fixed on MEA. When stimulated by the salt stimuli, electrophysiological activities of taste receptor cells in taste buds were measured through a multi-channel recording system. Both simulation and experiment results showed a dose-dependent increase in NaCl-induced potentials of taste receptor cells, which indicated good applications in salt measurements. The multi-channel analysis demonstrated that different groups of MEA channels were activated during stimulations, indicating non-overlapping populations of receptor cells in taste buds involved in salt taste perception. The study provides an effective and reliable biosensor platform to help recognize and distinguish salt taste components. Copyright © 2012 Elsevier B.V. All rights reserved.

Complex analysis of neuronal spike trains of deep brain nuclei in patients with Parkinson's disease.

PubMed

Chan, Hsiao-Lung; Lin, Ming-An; Lee, Shih-Tseng; Tsai, Yu-Tai; Chao, Pei-Kuang; Wu, Tony

2010-04-05

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been used to alleviate symptoms of Parkinson's disease. During image-guided stereotactic surgery, signals from microelectrode recordings are used to distinguish the STN from adjacent areas, particularly from the substantia nigra pars reticulata (SNr). Neuronal firing patterns based on interspike intervals (ISI) are commonly used. In the present study, arrival time-based measures, including Lempel-Ziv complexity and deviation-from-Poisson index were employed. Our results revealed significant differences in the arrival time-based measures among non-motor STN, motor STN and SNr and better discrimination than the ISI-based measures. The larger deviations from the Poisson process in the SNr implied less complex dynamics of neuronal discharges. If spike classification was not used, the arrival time-based measures still produced statistical differences among STN subdivisions and SNr, but the ISI-based measures only showed significant differences between motor and non-motor STN. Arrival time-based measures are less affected by spike misclassifications, and may be used as an adjunct for the identification of the STN during microelectrode targeting. Copyright 2010 Elsevier Inc. All rights reserved.

Dynamics of Single Hydrogen Bubbles at a Platinum Microelectrode.

PubMed

Yang, Xuegeng; Karnbach, Franziska; Uhlemann, Margitta; Odenbach, Stefan; Eckert, Kerstin

2015-07-28

Bubble dynamics, including the formation, growth, and detachment, of single H2 bubbles was studied at a platinum microelectrode during the electrolysis of 1 M H2SO4 electrolyte. The bubbles were visualized through a microscope by a high-speed camera. Electrochemical measurements were conducted in parallel to measure the transient current. The periodic current oscillations, resulting from the periodic formation and detachment of single bubbles, allow the bubble lifetime and size to be predicted from the transient current. A comparison of the bubble volume calculated from the current and from the recorded bubble image shows a gas evolution efficiency increasing continuously with the growth of the bubble until it reaches 100%. Two different substrates, glass and epoxy, were used to embed the Pt wire. While nearly no difference was found with respect to the growth law for the bubble radius, the contact angle differs strongly for the two types of cell. Data provided for the contact point evolution further complete the image of single hydrogen bubble growth. Finally, the velocity field driven by the detached bubble was measured by means of PIV, and the effects of the convection on the subsequent bubble were evaluated.

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.

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.

A new kind of universal smart home security safety monitoring system

NASA Astrophysics Data System (ADS)

Li, Biqing; Li, Zhao

2018-04-01

With the current level of social development, improved quality of life, existence and security issues of law and order has become an important issue. This graduation project adopts the form of wireless transmission, to STC89C52 microcontroller as the host control human infrared induction anti-theft monitoring system. The system mainly consists of main control circuit, power supply circuit, activities of the human body detection module, sound and light alarm circuit, record and display circuit. The main function is to achieve exploration activities on the human body, then the information is transmitted to the control panel, according to the system microcontroller program control sound and light alarm circuit, while recording the alarm location and time, and always check the record as required, and ultimately achieve the purpose of monitoring. The advantage of using pyroelectric infrared sensor can be installed in a hidden place, not easy to find, and low cost, good detection results, and has broad prospects for development.

Fabrication and modeling of stretchable conductors for traumatic brain injury research

NASA Astrophysics Data System (ADS)

Cao, Wenzhe

Stretchable electronics are an emergent class of electronics that can retain their electric functionality under large mechanical deformation, such as stretching, bending and compression. Like traditional electric circuits, stretchable electronics rely on electrical conductors, but in this specific instance the conductors must also be stretchable. This thesis research had three goals: (1) fabricate elastically stretchable conductors that retain their electrical conductance when stretched by tens of percent of strain; (2) understand the underlying stretching mechanism of gold conductors on polydimethylsiloxane (PDMS) substrates; (3) produce a special device---a stretchable microelectrode array, which contains a matrix of stretchable conductors that enables a new approach to studying traumatic brain injury. We first developed and optimized the micro-fabrication process to make elastically stretchable thin gold film conductors on PDMS substrates. The conductors can retain electrical conduction while being stretched reversibly to 140% uniaxially and 16% radially. We further developed a fabrication process to encapsulate the conductors with either a commercially available photopatternable silicone (PPS) or with PDMS. 100 microm by 100 microm vias were patterned in the encapsulation layer to expose electrical contacts. PPS encapsulated conductors can be stretched uniaxially to 80%, and the PDMS encapsulated conductor can be stretched to ˜15%, without losing electrical conduction. We also introduced acrylate-based shape memory polymers (SMPs) as a new type of substrate for stretchable conductors. Their stiffness can be tuned by varying the monomer composition or by changing the ambient temperature. Thin gold film conductors deposited on pre-strained SMPs remain conductive when first stretched and then relaxed to their pre-strain value. Moreover, an SMP can also serve as a stretchable carrier to make pre-strained conductors on an overlying PDMS membrane. The resistance of gold conductors made on pre-strained PDMS changes less during stretching than that made on non-pre-strained PDMS substrate. We built a model of the electrical resistance in function of strain. The model is based on the topography of the thin gold film on PDMS. This model is a first attempt at predicting electrical resistance of stretchable thin gold film conductors. Lastly, we fabricated stretchable microelectrode arrays (SMEAs). They were utilized at Columbia University to study traumatic brain injury (TBI). Tissues cultured on SMEA remained viable for 19 days, and the electrodes were able to both stimulate and record neural tissue activity before, during and after stretching. Therefore SMEAs are able to bring together mechanical injury, electrophysiological recording and pharmacological studies. The SMEAs could serve as in vitro platforms for high throughput therapeutic screening and discovery for traumatic injury. The ability to reproducibly fabricate stretchable conductors using micro-fabrication technology will facilitate adoption by industry. The ability to understand the stretching mechanism will enable us to design more robust material systems. The SMEA prototypes demonstrate that stretchable conductors are practical, and their mechanical compatibility with biological systems also makes them candidates for use in biomedical devices.

NeuroMap: A Spline-Based Interactive Open-Source Software for Spatiotemporal Mapping of 2D and 3D MEA Data

PubMed Central

Abdoun, Oussama; Joucla, Sébastien; Mazzocco, Claire; Yvert, Blaise

2010-01-01

A major characteristic of neural networks is the complexity of their organization at various spatial scales, from microscopic local circuits to macroscopic brain-scale areas. Understanding how neural information is processed thus entails the ability to study them at multiple scales simultaneously. This is made possible using microelectrodes array (MEA) technology. Indeed, high-density MEAs provide large-scale coverage (several square millimeters) of whole neural structures combined with microscopic resolution (about 50 μm) of unit activity. Yet, current options for spatiotemporal representation of MEA-collected data remain limited. Here we present NeuroMap, a new interactive Matlab-based software for spatiotemporal mapping of MEA data. NeuroMap uses thin plate spline interpolation, which provides several assets with respect to conventional mapping methods used currently. First, any MEA design can be considered, including 2D or 3D, regular or irregular, arrangements of electrodes. Second, spline interpolation allows the estimation of activity across the tissue with local extrema not necessarily at recording sites. Finally, this interpolation approach provides a straightforward analytical estimation of the spatial Laplacian for better current sources localization. In this software, coregistration of 2D MEA data on the anatomy of the neural tissue is made possible by fine matching of anatomical data with electrode positions using rigid-deformation-based correction of anatomical pictures. Overall, NeuroMap provides substantial material for detailed spatiotemporal analysis of MEA data. The package is distributed under GNU General Public License and available at http://sites.google.com/site/neuromapsoftware. PMID:21344013

NeuroMap: A Spline-Based Interactive Open-Source Software for Spatiotemporal Mapping of 2D and 3D MEA Data.

PubMed

Abdoun, Oussama; Joucla, Sébastien; Mazzocco, Claire; Yvert, Blaise

2011-01-01

A major characteristic of neural networks is the complexity of their organization at various spatial scales, from microscopic local circuits to macroscopic brain-scale areas. Understanding how neural information is processed thus entails the ability to study them at multiple scales simultaneously. This is made possible using microelectrodes array (MEA) technology. Indeed, high-density MEAs provide large-scale coverage (several square millimeters) of whole neural structures combined with microscopic resolution (about 50 μm) of unit activity. Yet, current options for spatiotemporal representation of MEA-collected data remain limited. Here we present NeuroMap, a new interactive Matlab-based software for spatiotemporal mapping of MEA data. NeuroMap uses thin plate spline interpolation, which provides several assets with respect to conventional mapping methods used currently. First, any MEA design can be considered, including 2D or 3D, regular or irregular, arrangements of electrodes. Second, spline interpolation allows the estimation of activity across the tissue with local extrema not necessarily at recording sites. Finally, this interpolation approach provides a straightforward analytical estimation of the spatial Laplacian for better current sources localization. In this software, coregistration of 2D MEA data on the anatomy of the neural tissue is made possible by fine matching of anatomical data with electrode positions using rigid-deformation-based correction of anatomical pictures. Overall, NeuroMap provides substantial material for detailed spatiotemporal analysis of MEA data. The package is distributed under GNU General Public License and available at http://sites.google.com/site/neuromapsoftware.

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.

A closed-loop compressive-sensing-based neural recording system.

PubMed

Zhang, Jie; Mitra, Srinjoy; Suo, Yuanming; Cheng, Andrew; Xiong, Tao; Michon, Frederic; Welkenhuysen, Marleen; Kloosterman, Fabian; Chin, Peter S; Hsiao, Steven; Tran, Trac D; Yazicioglu, Firat; Etienne-Cummings, Ralph

2015-06-01

This paper describes a low power closed-loop compressive sensing (CS) based neural recording system. This system provides an efficient method to reduce data transmission bandwidth for implantable neural recording devices. By doing so, this technique reduces a majority of system power consumption which is dissipated at data readout interface. The design of the system is scalable and is a viable option for large scale integration of electrodes or recording sites onto a single device. The entire system consists of an application-specific integrated circuit (ASIC) with 4 recording readout channels with CS circuits, a real time off-chip CS recovery block and a recovery quality evaluation block that provides a closed feedback to adaptively adjust compression rate. Since CS performance is strongly signal dependent, the ASIC has been tested in vivo and with standard public neural databases. Implemented using efficient digital circuit, this system is able to achieve >10 times data compression on the entire neural spike band (500-6KHz) while consuming only 0.83uW (0.53 V voltage supply) additional digital power per electrode. When only the spikes are desired, the system is able to further compress the detected spikes by around 16 times. Unlike other similar systems, the characteristic spikes and inter-spike data can both be recovered which guarantes a >95% spike classification success rate. The compression circuit occupied 0.11mm(2)/electrode in a 180nm CMOS process. The complete signal processing circuit consumes <16uW/electrode. Power and area efficiency demonstrated by the system make it an ideal candidate for integration into large recording arrays containing thousands of electrode. Closed-loop recording and reconstruction performance evaluation further improves the robustness of the compression method, thus making the system more practical for long term recording.

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...

Telescience testbed experiments for biomedical studies: fertilization potential recording of amphibian eggs using tele-manipulation under stereoscopic vision.

PubMed

Watanabe, S; Tanaka, M; Wada, Y; Suzuki, H; Takagi, S; Mori, S; Fukai, K; Kanazawa, Y; Takagi, M; Hirakawa, K; Ogasawara, K; Tsumura, K; Ogawa, K; Matsumoto, K; Nagaoka, S; Suzuki, T; Shimura, D; Yamashita, M; Nishio, S

1994-07-01

The telescience testbed experiments were carried out to test and investigate the tele-manipulation techniques in the intracellular potential recording of amphibian eggs. Implementation of telescience testbed was set up in the two separated laboratories of the Tsukuba Space center of NASDA, which were connected by tele-communication links. Manipulators respective for a microelectrode and a sample stage of microscope were moved by computers, of which command signals were transmitted from a computer in a remote control room. The computer in the control room was operated by an investigator (PI) who controlled the movement of each manipulator remotely. A stereoscopic vision of the microscope image were prepared by using a head mounted display (HMD) and were indispensable to the intracellular single cell recording. The fertilization potential of amphibian eggs was successfully obtained through the remote operating system.

Tracking individual action potentials throughout mammalian axonal arbors.

PubMed

Radivojevic, Milos; Franke, Felix; Altermatt, Michael; Müller, Jan; Hierlemann, Andreas; Bakkum, Douglas J

2017-10-09

Axons are neuronal processes specialized for conduction of action potentials (APs). The timing and temporal precision of APs when they reach each of the synapses are fundamentally important for information processing in the brain. Due to small diameters of axons, direct recording of single AP transmission is challenging. Consequently, most knowledge about axonal conductance derives from modeling studies or indirect measurements. We demonstrate a method to noninvasively and directly record individual APs propagating along millimeter-length axonal arbors in cortical cultures with hundreds of microelectrodes at microsecond temporal resolution. We find that cortical axons conduct single APs with high temporal precision (~100 µs arrival time jitter per mm length) and reliability: in more than 8,000,000 recorded APs, we did not observe any conduction or branch-point failures. Upon high-frequency stimulation at 100 Hz, successive became slower, and their arrival time precision decreased by 20% and 12% for the 100th AP, respectively.

Introductory overview of research instruments for recording the electrical activity of neurons in the human brain

NASA Astrophysics Data System (ADS)

Garell, P. C.; Granner, M. A.; Noh, M. D.; Howard, M. A.; Volkov, I. O.; Gillies, G. T.

1998-12-01

Scientific advancement is often spurred by the development of new instruments for investigation. Over the last several decades, many new instruments have been produced to further our understanding of the physiology of the human brain. We present a partial overview of some of these instruments, paying particular attention to those which record the electrical activity of the human brain. We preface the review with a brief primer on neuroanatomy and physiology, followed by a discussion of the latest types of apparatus used to investigate various properties of the central nervous system. A special focus is on microelectrode investigations that employ both intracellular and extracellular methods of recording the electrical activity of single neurons; another is on the modern electroencephalographic, electrocorticographic, and magnetoencephalographic methods used to study the spontaneous and evoked field potentials of the brain. Some examples of clinical applications are included, where appropriate.

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.

A Multipurpose CMOS Platform for Nanosensing

PubMed Central

Bonanno, Alberto; Sanginario, Alessandro; Marasso, Simone L.; Miccoli, Beatrice; Bejtka, Katarzyna; Benetto, Simone; Demarchi, Danilo

2016-01-01

This paper presents a customizable sensing system based on functionalized nanowires (NWs) assembled onto complementary metal oxide semiconductor (CMOS) technology. The Micro-for-Nano (M4N) chip integrates on top of the electronics an array of aluminum microelectrodes covered with gold by means of a customized electroless plating process. The NW assembly process is driven by an array of on-chip dielectrophoresis (DEP) generators, enabling a custom layout of different nanosensors on the same microelectrode array. The electrical properties of each assembled NW are singularly sensed through an in situ CMOS read-out circuit (ROC) that guarantees a low noise and reliable measurement. The M4N chip is directly connected to an external microcontroller for configuration and data processing. The processed data are then redirected to a workstation for real-time data visualization and storage during sensing experiments. As proof of concept, ZnO nanowires have been integrated onto the M4N chip to validate the approach that enables different kind of sensing experiments. The device has been then irradiated by an external UV source with adjustable power to measure the ZnO sensitivity to UV-light exposure. A maximum variation of about 80% of the ZnO-NW resistance has been detected by the M4N system when the assembled 5 μm × 500 nm single ZnO-NW is exposed to an estimated incident radiant UV-light flux in the range of 1 nW–229 nW. The performed experiments prove the efficiency of the platform conceived for exploiting any kind of material that can change its capacitance and/or resistance due to an external stimulus. PMID:27916911

A Multipurpose CMOS Platform for Nanosensing.

PubMed

Bonanno, Alberto; Sanginario, Alessandro; Marasso, Simone L; Miccoli, Beatrice; Bejtka, Katarzyna; Benetto, Simone; Demarchi, Danilo

2016-11-30

This paper presents a customizable sensing system based on functionalized nanowires (NWs) assembled onto complementary metal oxide semiconductor (CMOS) technology. The Micro-for-Nano (M4N) chip integrates on top of the electronics an array of aluminum microelectrodes covered with gold by means of a customized electroless plating process. The NW assembly process is driven by an array of on-chip dielectrophoresis (DEP) generators, enabling a custom layout of different nanosensors on the same microelectrode array. The electrical properties of each assembled NW are singularly sensed through an in situ CMOS read-out circuit (ROC) that guarantees a low noise and reliable measurement. The M4N chip is directly connected to an external microcontroller for configuration and data processing. The processed data are then redirected to a workstation for real-time data visualization and storage during sensing experiments. As proof of concept, ZnO nanowires have been integrated onto the M4N chip to validate the approach that enables different kind of sensing experiments. The device has been then irradiated by an external UV source with adjustable power to measure the ZnO sensitivity to UV-light exposure. A maximum variation of about 80% of the ZnO-NW resistance has been detected by the M4N system when the assembled 5 μ m × 500 nm single ZnO-NW is exposed to an estimated incident radiant UV-light flux in the range of 1 nW-229 nW. The performed experiments prove the efficiency of the platform conceived for exploiting any kind of material that can change its capacitance and/or resistance due to an external stimulus.

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.

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.

Implications of chronic daily anti-oxidant administration on the inflammatory response to intracortical microelectrodes

NASA Astrophysics Data System (ADS)

Potter-Baker, Kelsey A.; Stewart, Wade G.; Tomaszewski, William H.; Wong, Chun T.; Meador, William D.; Ziats, Nicholas P.; Capadona, Jeffrey R.

2015-08-01

Objective. Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes. Approach. Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg kg-1. The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/neuroprotection following device implantation. Main results. Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals. Significance. Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes.

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...

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...

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.

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.

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.

Flexible inorganic light emitting diodes and transparent PEDOT:PSS/Parylene C for simultaneous optogenetics and electrocorticography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lee, Keundong; Ganji, Mehran; Hossain, Lorraine; Ro, Yun Goo; Lee, Sang Heon; Park, Jong-woo; Yoo, Dongha; Yoon, Jiyoung; Yi, Gyu-Chul; Dayeh, Shadi A.

2017-02-01

Electrocorticography (ECoG) is a powerful tool for direct mapping of local field potentials from the brain surface. Progress in development of high-fidelity materials such as poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) on thin conformal substrates such as parylene C enabled intimate contact with cortical surfaces and higher quality recordings from small volumes of neurons. Meanwhile, stimulation of neuronal activity is conventionally accomplished with electrical microstimulation and transcranial magnetic stimulation that can be combined with ECoG to form the basis of bidirectional neural interface. However, these stimulation mechanisms are less controlled and primitively understood on the local and cellular levels. With the advent of optogenetics, the localization and specificity of neuronal stimulation and inhibition is possible. Therefore, the development of integrated devices that can merge the sensitivity of ECoG or depth recording with optogenetic tools can lead to newer frontiers in understanding the neuronal activity. Herein, we introduce a hybrid device comprising flexible inorganic LED arrays integrated PEDOT:PSS/parylene C microelectrode arrays for high resolution bidirectional neuronal interfaces. The flexible inorganic LEDs have been developed by the metal-organic vapor phase epitaxy of position-controlled GaN microLEDs on ZnO nanostructured templates pre-grown at precise locations on a graphene layer. By transferring it onto the microelectrode arrays, it can provides the individual electrical addressability by light stimulation patterns. We will present experimental and simulation results on the optoelectronic characteristics and light activation capability of flexible microLEDs and their evaluation in vivo.

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.

Electrophysiological Recordings from the Giant Fiber System

PubMed Central

Allen, Marcus J

2010-01-01

The giant fiber system (GFS) of Drosophila is a well-characterized neuronal circuit that mediates the escape response in the fly. It is one of the few adult neural circuits from which electrophysiological recordings can be made routinely. This article describes a simple procedure for stimulating the giant fiber neurons directly in the brain of the adult fly and obtaining recordings from the output muscles of the giant fiber system. PMID:20647357

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

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.

Extracellular Recordings of Patterned Human Pluripotent Stem Cell-Derived Cardiomyocytes on Aligned Fibers.

PubMed

Li, Junjun; Minami, Itsunari; Yu, Leqian; Tsuji, Kiyotaka; Nakajima, Minako; Qiao, Jing; Suzuki, Masato; Shimono, Ken; Nakatsuji, Norio; Kotera, Hitetoshi; Liu, Li; Chen, Yong

2016-01-01

Human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (CMs) hold high potential for use in drug assessment and myocardial regeneration. To create tissue-like constructs of CMs for extracellular monitoring, we placed aligned fibers (AFs) on the surface of a microelectrode array and then seeded hiPSC-CMs for subsequent monitoring for 14 days. As expected, the CMs organized into anisotropic and matured tissue and the extracellular recordings showed reduced premature beating higher signal amplitude and a higher probability of T-wave detection as compared to the culture without fibers. The CMs on the aligned fibers samples also exhibited anisotropic propagation of the field potential. These results therefore suggest that the hiPSC-CMs cultured on AFs can be used more reliably for cell based assays.

Extracellular Recordings of Patterned Human Pluripotent Stem Cell-Derived Cardiomyocytes on Aligned Fibers

PubMed Central

Minami, Itsunari; Yu, Leqian; Nakajima, Minako; Qiao, Jing; Shimono, Ken; Nakatsuji, Norio; Kotera, Hitetoshi; Chen, Yong

2016-01-01

Human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (CMs) hold high potential for use in drug assessment and myocardial regeneration. To create tissue-like constructs of CMs for extracellular monitoring, we placed aligned fibers (AFs) on the surface of a microelectrode array and then seeded hiPSC-CMs for subsequent monitoring for 14 days. As expected, the CMs organized into anisotropic and matured tissue and the extracellular recordings showed reduced premature beating higher signal amplitude and a higher probability of T-wave detection as compared to the culture without fibers. The CMs on the aligned fibers samples also exhibited anisotropic propagation of the field potential. These results therefore suggest that the hiPSC-CMs cultured on AFs can be used more reliably for cell based assays. PMID:27446217

76 FR 15340 - In the Matter of Certain GPS Devices and Products Containing Same; Notice of Commission...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-21

....usitc.gov . The public record for this investigation may be viewed on the Commission's electronic docket... Circuit (``Federal Circuit''). On April 12, 2010, the Federal Circuit affirmed the Commission's Final...

Effects of Ag+ on ion transport by the corneal epithelium of the rabbit.

PubMed

Klyce, S D; Marshall, W S

1982-01-01

Exposure of the in vitro rabbit corneal epithelium to Ag+ by the addition of AgNO3 (10(-7)-10(-5) M) to the apical surface or by the use of imperfectly chlorided Ag/AgCl half-cells in Ussing-style membrane chambers, greatly increases short-circuit current and transepithelial potential. The early phase (the first 30 min) of the short-circuit current stimulation by Ag+ is linearly dependent on tear-side sodium concentration, is largely a result of a tenfold increase in net Na+ uptake and is incompletely inhibited by ouabain, suggesting that Ag+ increases cation (primarily Na+) conductance of the apical membrane. This mechanism for the Ag+ effect is supported by microelectrode experiments, wherein Ag+ depolarizes specifically the apical barrier potential and increases apical barrier conductance. A later phase in the effect (0.5-3 hr) is characterized by a gradual increase in 36Cl- and 14C-mannitol unidirectional fluxes, by a decline in epithelial resting potential and short-circuit current, by complete ouabain inhibition and by fit to saturation kinetics with respect to Na+ concentration in the bathing media. This phase of the effect apparently reflects a nonselective opening of the paracellular pathway in the epithelium and is rate-limited by Na+ pump activity at the basolateral membrane. Both phases are associated with swelling of the corneal stroma and may be rapidly reversed using thiol agents (reduced glutathione and dithiothreitol). The results suggest that Ag+ may be useful in the study of cation transport by epithelia and the work provides basic physiological information that is pertinent to the prophylactic use of AgNO3 in clinical ophthalmology.

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...

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

Cell-substrate impedance fluctuations of single amoeboid cells encode cell-shape and adhesion dynamics

NASA Astrophysics Data System (ADS)

Leonhardt, Helmar; Gerhardt, Matthias; Höppner, Nadine; Krüger, Kirsten; Tarantola, Marco; Beta, Carsten

2016-01-01

We show systematic electrical impedance measurements of single motile cells on microelectrodes. Wild-type cells and mutant strains were studied that differ in their cell-substrate adhesion strength. We recorded the projected cell area by time-lapse microscopy and observed irregular oscillations of the cell shape. These oscillations were correlated with long-term variations in the impedance signal. Superposed to these long-term trends, we observed fluctuations in the impedance signal. Their magnitude clearly correlated with the adhesion strength, suggesting that strongly adherent cells display more dynamic cell-substrate interactions.

A system for multichannel recording and automatic reading of information. [for onboard cosmic ray counter

NASA Technical Reports Server (NTRS)

Bogomolov, E. A.; Yevstafev, Y. Y.; Karakadko, V. K.; Lubyanaya, N. D.; Romanov, V. A.; Totubalina, M. G.; Yamshchikov, M. A.

1975-01-01

A system for the recording and processing of telescope data is considered for measurements of EW asymmetry. The information is recorded by 45 channels on a continuously moving 35-mm film. The dead time of the recorder is about 0.1 sec. A sorting electronic circuit is used to reduce the errors when the statistical time distribution of the pulses is recorded. The recorded information is read out by means of photoresistors. The phototransmitter signals are fed either to the mechanical recorder unit for preliminary processing, or to a logical circuit which controls the operation of the punching device. The punched tape is processed by an electronic computer.

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

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

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.

System for Multiplexing Acoustic Emission (AE) Instrumentation

NASA Technical Reports Server (NTRS)

Prosser, William H. (Inventor); Perey, Daniel F. (Inventor); Gorman, Michael R. (Inventor); Scales, Edgar F. (Inventor)

2003-01-01

An acoustic monitoring device has at least two acoustic sensors with a triggering mechanism and a multiplexing circuit. After the occurrence of a triggering event at a sensor, the multiplexing circuit allows a recording component to record acoustic emissions at adjacent sensors. The acoustic monitoring device is attached to a solid medium to detect the occurrence of damage.

Model-based evaluation of the short-circuited tripolar cuff configuration.

PubMed

Andreasen, Lotte N S; Struijk, Johannes J

2006-05-01

Recordings of neural information for use as feedback in functional electrical stimulation are often contaminated with interfering signals from muscles and from stimulus pulses. The cuff electrode used for the neural recording can be optimized to improve the S/I ratio. In this work, we evaluate a model of both the nerve signal and the interfering signals recorded by a cuff, and subsequently use this model to study the signal to interference ratio of different cuff designs and to evaluate a recently introduced short-circuited tripolar cuff configuration. The results of the model showed good agreement with results from measurements in rabbits and confirmed the superior performance of the short-circuited tripolar configuration as compared with the traditionally used tripolar configuration.

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.

Lab-on-CMOS Integration of Microfluidics and Electrochemical Sensors

PubMed Central

Huang, Yue; Mason, Andrew J.

2013-01-01

This paper introduces a CMOS-microfluidics integration scheme for electrochemical microsystems. A CMOS chip was embedded into a micro-machined silicon carrier. By leveling the CMOS chip and carrier surface to within 100 nm, an expanded obstacle-free surface suitable for photolithography was achieved. Thin film metal planar interconnects were microfabricated to bridge CMOS pads to the perimeter of the carrier, leaving a flat and smooth surface for integrating microfluidic structures. A model device containing SU-8 microfluidic mixers and detection channels crossing over microelectrodes on a CMOS integrated circuit was constructed using the chip-carrier assembly scheme. Functional integrity of microfluidic structures and on-CMOS electrodes was verified by a simultaneous sample dilution and electrochemical detection experiment within multi-channel microfluidics. This lab-on-CMOS integration process is capable of high packing density, is suitable for wafer-level batch production, and opens new opportunities to combine the performance benefits of on-CMOS sensors with lab-on-chip platforms. PMID:23939616

Lab-on-CMOS integration of microfluidics and electrochemical sensors.

PubMed

Huang, Yue; Mason, Andrew J

2013-10-07

This paper introduces a CMOS-microfluidics integration scheme for electrochemical microsystems. A CMOS chip was embedded into a micro-machined silicon carrier. By leveling the CMOS chip and carrier surface to within 100 nm, an expanded obstacle-free surface suitable for photolithography was achieved. Thin film metal planar interconnects were microfabricated to bridge CMOS pads to the perimeter of the carrier, leaving a flat and smooth surface for integrating microfluidic structures. A model device containing SU-8 microfluidic mixers and detection channels crossing over microelectrodes on a CMOS integrated circuit was constructed using the chip-carrier assembly scheme. Functional integrity of microfluidic structures and on-CMOS electrodes was verified by a simultaneous sample dilution and electrochemical detection experiment within multi-channel microfluidics. This lab-on-CMOS integration process is capable of high packing density, is suitable for wafer-level batch production, and opens new opportunities to combine the performance benefits of on-CMOS sensors with lab-on-chip platforms.

Ultrasensitive and label-free detection of pathogenic avian influenza DNA by using CMOS impedimetric sensors.

PubMed

Lai, Wei-An; Lin, Chih-Heng; Yang, Yuh-Shyong; Lu, Michael S-C

2012-05-15

This work presents miniaturized CMOS (complementary metal oxide semiconductor) sensors for non-faradic impedimetric detection of AIV (avian influenza virus) oligonucleotides. The signal-to-noise ratio is significantly improved by monolithic sensor integration to reduce the effect of parasitic capacitances. The use of sub-μm interdigitated microelectrodes is also beneficial for promoting the signal coupling efficiency. Capacitance changes associated with surface modification, functionalization, and DNA hybridization were extracted from the measured frequency responses based on an equivalent-circuit model. Hybridization of the AIV H5 capture and target DNA probes produced a capacitance reduction of -13.2 ± 2.1% for target DNA concentrations from 1 fM to 10 fM, while a capacitance increase was observed when H5 target DNA was replaced with non-complementary H7 target DNA. With the demonstrated superior sensing capabilities, this miniaturized CMOS sensing platform shows great potential for label-free point-of-care biosensing applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Digital micromirror based near-infrared illumination system for plasmonic photothermal neuromodulation.

PubMed

Jung, Hyunjun; Kang, Hongki; Nam, Yoonkey

2017-06-01

Light-mediated neuromodulation techniques provide great advantages to investigate neuroscience due to its high spatial and temporal resolution. To generate a spatial pattern of neural activity, it is necessary to develop a system for patterned-light illumination to a specific area. Digital micromirror device (DMD) based patterned illumination system have been used for neuromodulation due to its simple configuration and design flexibility. In this paper, we developed a patterned near-infrared (NIR) illumination system for region specific photothermal manipulation of neural activity using NIR-sensitive plasmonic gold nanorods (GNRs). The proposed system had high power transmission efficiency for delivering power density up to 19 W/mm 2 . We used a GNR-coated microelectrode array (MEA) to perform biological experiments using E18 rat hippocampal neurons and showed that it was possible to inhibit neural spiking activity of specific area in neural circuits with the patterned NIR illumination. This patterned NIR illumination system can serve as a promising neuromodulation tool to investigate neuroscience in a wide range of physiological and clinical applications.

PCACE- PERSONAL COMPUTER AIDED CABLING ENGINEERING

NASA Technical Reports Server (NTRS)

Billitti, J. W.

1994-01-01

A computerized interactive harness engineering program has been developed to provide an inexpensive, interactive system which is designed for learning and using an engineering approach to interconnection systems. PCACE is basically a database system that stores information as files of individual connectors and handles wiring information in circuit groups stored as records. This directly emulates the typical manual engineering methods of data handling, thus making the user interface to the program very natural. Data files can be created, viewed, manipulated, or printed in real time. The printed ouput is in a form ready for use by fabrication and engineering personnel. PCACE also contains a wide variety of error-checking routines including connector contact checks during hardcopy generation. The user may edit existing harness data files or create new files. In creating a new file, the user is given the opportunity to insert all the connector and harness boiler plate data which would be part of a normal connector wiring diagram. This data includes the following: 1) connector reference designator, 2) connector part number, 3) backshell part number, 4) cable reference designator, 5) cable part number, 6) drawing revision, 7) relevant notes, 8) standard wire gauge, and 9) maximum circuit count. Any item except the maximum circuit count may be left blank, and any item may be changed at a later time. Once a file is created and organized, the user is directed to the main menu and has access to the file boiler plate, the circuit wiring records, and the wiring records index list. The organization of a file is such that record zero contains the connector/cable boiler plate, and all other records contain circuit wiring data. Each wiring record will handle a circuit with as many as nine wires in the interface. The record stores the circuit name and wire count and the following data for each wire: 1) wire identifier, 2) contact, 3) splice, 4) wire gauge if different from standard, 5) wire/group type, 6) wire destination, and 7) note number. The PCACE record structure allows for a wide variety of wiring forms using splices and shields, yet retains sufficient structure to maintain ease of use. PCACE is written in TURBO Pascal 3.0 and has been implemented on IBM PC, XT, and AT systems under DOS 3.1 with a memory of 512K of 8 bit bytes, two floppy disk drives, an RGB monitor, and a printer with ASCII control characters. PCACE was originally developed in 1983, and the IBM version was released in 1986.

Depth-time interpolation of feature trends extracted from mobile microelectrode data with kernel functions.

PubMed

Wong, Stephen; Hargreaves, Eric L; Baltuch, Gordon H; Jaggi, Jurg L; Danish, Shabbar F

2012-01-01

Microelectrode recording (MER) is necessary for precision localization of target structures such as the subthalamic nucleus during deep brain stimulation (DBS) surgery. Attempts to automate this process have produced quantitative temporal trends (feature activity vs. time) extracted from mobile MER data. Our goal was to evaluate computational methods of generating spatial profiles (feature activity vs. depth) from temporal trends that would decouple automated MER localization from the clinical procedure and enhance functional localization in DBS surgery. We evaluated two methods of interpolation (standard vs. kernel) that generated spatial profiles from temporal trends. We compared interpolated spatial profiles to true spatial profiles that were calculated with depth windows, using correlation coefficient analysis. Excellent approximation of true spatial profiles is achieved by interpolation. Kernel-interpolated spatial profiles produced superior correlation coefficient values at optimal kernel widths (r = 0.932-0.940) compared to standard interpolation (r = 0.891). The choice of kernel function and kernel width resulted in trade-offs in smoothing and resolution. Interpolation of feature activity to create spatial profiles from temporal trends is accurate and can standardize and facilitate MER functional localization of subcortical structures. The methods are computationally efficient, enhancing localization without imposing additional constraints on the MER clinical procedure during DBS surgery. Copyright © 2012 S. Karger AG, Basel.

Propagating Neural Source Revealed by Doppler Shift of Population Spiking Frequency

PubMed Central

Zhang, Mingming; Shivacharan, Rajat S.; Chiang, Chia-Chu; Gonzalez-Reyes, Luis E.

2016-01-01

Electrical activity in the brain during normal and abnormal function is associated with propagating waves of various speeds and directions. It is unclear how both fast and slow traveling waves with sometime opposite directions can coexist in the same neural tissue. By recording population spikes simultaneously throughout the unfolded rodent hippocampus with a penetrating microelectrode array, we have shown that fast and slow waves are causally related, so a slowly moving neural source generates fast-propagating waves at ∼0.12 m/s. The source of the fast population spikes is limited in space and moving at ∼0.016 m/s based on both direct and Doppler measurements among 36 different spiking trains among eight different hippocampi. The fact that the source is itself moving can account for the surprising direction reversal of the wave. Therefore, these results indicate that a small neural focus can move and that this phenomenon could explain the apparent wave reflection at tissue edges or multiple foci observed at different locations in neural tissue. SIGNIFICANCE STATEMENT The use of novel techniques with an unfolded hippocampus and penetrating microelectrode array to record and analyze neural activity has revealed the existence of a source of neural signals that propagates throughout the hippocampus. The source itself is electrically silent, but its location can be inferred by building isochrone maps of population spikes that the source generates. The movement of the source can also be tracked by observing the Doppler frequency shift of these spikes. These results have general implications for how neural signals are generated and propagated in the hippocampus; moreover, they have important implications for the understanding of seizure generation and foci localization. PMID:27013678

Comparative study of microelectrode recording-based STN location and MRI-based STN location in low to ultra-high field (7.0 T) T2-weighted MRI images

NASA Astrophysics Data System (ADS)

Verhagen, Rens; Schuurman, P. Richard; van den Munckhof, Pepijn; Fiorella Contarino, M.; de Bie, Rob M. A.; Bour, Lo J.

2016-12-01

Objective. The correspondence between the anatomical STN and the STN observed in T2-weighted MRI images used for deep brain stimulation (DBS) targeting remains unclear. Using a new method, we compared the STN borders seen on MRI images with those estimated by intraoperative microelectrode recordings (MER). Approach. We developed a method to automatically generate a detailed estimation of STN shape and the location of its borders, based on multiple-channel MER measurements. In 33 STNs of 19 Parkinson patients, we quantitatively compared the dorsal and lateral borders of this MER-based STN model with the STN borders visualized by 1.5 T (n = 14), 3.0 T (n = 10) and 7.0 T (n = 9) T2-weighted MRI. Main results. The dorsal border was identified more dorsally on coronal T2 MRI than by the MER-based STN model, with a significant difference in the 3.0 T (range 0.97-1.19 mm) and 7.0 T (range 1.23-1.25 mm) groups. The lateral border was significantly more medial on 1.5 T (mean: 1.97 mm) and 3.0 T (mean: 2.49 mm) MRI than in the MER-based STN; a difference that was not found in the 7.0 T group. Significance. The STN extends further in the dorsal direction on coronal T2 MRI images than is measured by MER. Increasing MRI field strength to 3.0 T or 7.0 T yields similar discrepancies between MER and MRI at the dorsal STN border. In contrast, increasing MRI field strength to 7.0 T may be useful for identification of the lateral STN border and thereby improve DBS targeting.

Microelectrode array recordings of cardiac action potentials as a high throughput method to evaluate pesticide toxicity.

PubMed

Natarajan, A; Molnar, P; Sieverdes, K; Jamshidi, A; Hickman, J J

2006-04-01

The threat of environmental pollution, biological warfare agent dissemination and new diseases in recent decades has increased research into cell-based biosensors. The creation of this class of sensors could specifically aid the detection of toxic chemicals and their effects in the environment, such as pyrethroid pesticides. Pyrethroids are synthetic pesticides that have been used increasingly over the last decade to replace other pesticides like DDT. In this study we used a high-throughput method to detect pyrethroids by using multielectrode extracellular recordings from cardiac cells. The data from this cell-electrode hybrid system was compared to published results obtained with patch-clamp electrophysiology and also used as an alternative method to further understand pyrethroid effects. Our biosensor consisted of a confluent monolayer of cardiac myocytes cultured on microelectrode arrays (MEA) composed of 60 substrate-integrated electrodes. Spontaneous activity of these beating cells produced extracellular field potentials in the range of 100 microV to nearly 1200 microV with a beating frequency of 0.5-4 Hz. All of the tested pyrethroids; alpha-Cypermethrin, Tetramethrin and Tefluthrin, produced similar changes in the electrophysiological properties of the cardiac myocytes, namely reduced beating frequency and amplitude. The sensitivity of our toxin detection method was comparable to earlier patch-clamp studies, which indicates that, in specific applications, high-throughput extracellular methods can replace single-cell studies. Moreover, the similar effect of all three pyrethroids on the measured parameters suggests, that not only detection of the toxins but, their classification might also be possible with this method. Overall our results support the idea that whole cell biosensors might be viable alternatives when compared to current toxin detection methods.

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.

Cell culture chamber with gas supply for prolonged recording of human neuronal cells on microelectrode array.

PubMed

Kreutzer, Joose; Ylä-Outinen, Laura; Mäki, Antti-Juhana; Ristola, Mervi; Narkilahti, Susanna; Kallio, Pasi

2017-03-15

Typically, live cell analyses are performed outside an incubator in an ambient air, where the lack of sufficient CO 2 supply results in a fast change of pH and the high evaporation causes concentration drifts in the culture medium. That limits the experiment time for tens of minutes. In many applications, e.g. in neurotoxicity studies, a prolonged measurement of extracellular activity is, however, essential. We demonstrate a simple cell culture chamber that enables stable culture conditions during prolonged extracellular recordings on a microelectrode array (MEA) outside an incubator. The proposed chamber consists of a gas permeable silicone structure that enables gas transfer into the chamber. We show that the culture chamber supports the growth of the human embryonic stem cell (hESC)-derived neurons both inside and outside an incubator. The structure provides very low evaporation, stable pH and osmolarity, and maintains strong signaling of hESC-derived neuronal networks over three-day MEA experiments. Existing systems are typically complex including continuous perfusion of medium or relatively large amount of gas to supply. The proposed chamber requires only a supply of very low flow rate (1.5ml/min) of non-humidified 5% CO 2 gas. Utilizing dry gas supply makes the proposed chamber simple to use. Using the proposed culture structure on top of MEA, we can maintain hESC-derived neural networks over three days outside an incubator. Technically, the structure requires very low flow rate of dry gas supporting, however, low evaporation and maintaining the pH of the culture. Copyright © 2017 Elsevier B.V. All rights reserved.

Near-field electromagnetic holography for high-resolution analysis of network interactions in neuronal tissue

PubMed Central

Kjeldsen, Henrik D.; Kaiser, Marcus; Whittington, Miles A.

2015-01-01

Background Brain function is dependent upon the concerted, dynamical interactions between a great many neurons distributed over many cortical subregions. Current methods of quantifying such interactions are limited by consideration only of single direct or indirect measures of a subsample of all neuronal population activity. New method Here we present a new derivation of the electromagnetic analogy to near-field acoustic holography allowing high-resolution, vectored estimates of interactions between sources of electromagnetic activity that significantly improves this situation. In vitro voltage potential recordings were used to estimate pseudo-electromagnetic energy flow vector fields, current and energy source densities and energy dissipation in reconstruction planes at depth into the neural tissue parallel to the recording plane of the microelectrode array. Results The properties of the reconstructed near-field estimate allowed both the utilization of super-resolution techniques to increase the imaging resolution beyond that of the microelectrode array, and facilitated a novel approach to estimating causal relationships between activity in neocortical subregions. Comparison with existing methods The holographic nature of the reconstruction method allowed significantly better estimation of the fine spatiotemporal detail of neuronal population activity, compared with interpolation alone, beyond the spatial resolution of the electrode arrays used. Pseudo-energy flow vector mapping was possible with high temporal precision, allowing a near-realtime estimate of causal interaction dynamics. Conclusions Basic near-field electromagnetic holography provides a powerful means to increase spatial resolution from electrode array data with careful choice of spatial filters and distance to reconstruction plane. More detailed approaches may provide the ability to volumetrically reconstruct activity patterns on neuronal tissue, but the ability to extract vectored data with the method presented already permits the study of dynamic causal interactions without bias from any prior assumptions on anatomical connectivity. PMID:26026581

Near-field electromagnetic holography for high-resolution analysis of network interactions in neuronal tissue.

PubMed

Kjeldsen, Henrik D; Kaiser, Marcus; Whittington, Miles A

2015-09-30

Brain function is dependent upon the concerted, dynamical interactions between a great many neurons distributed over many cortical subregions. Current methods of quantifying such interactions are limited by consideration only of single direct or indirect measures of a subsample of all neuronal population activity. Here we present a new derivation of the electromagnetic analogy to near-field acoustic holography allowing high-resolution, vectored estimates of interactions between sources of electromagnetic activity that significantly improves this situation. In vitro voltage potential recordings were used to estimate pseudo-electromagnetic energy flow vector fields, current and energy source densities and energy dissipation in reconstruction planes at depth into the neural tissue parallel to the recording plane of the microelectrode array. The properties of the reconstructed near-field estimate allowed both the utilization of super-resolution techniques to increase the imaging resolution beyond that of the microelectrode array, and facilitated a novel approach to estimating causal relationships between activity in neocortical subregions. The holographic nature of the reconstruction method allowed significantly better estimation of the fine spatiotemporal detail of neuronal population activity, compared with interpolation alone, beyond the spatial resolution of the electrode arrays used. Pseudo-energy flow vector mapping was possible with high temporal precision, allowing a near-realtime estimate of causal interaction dynamics. Basic near-field electromagnetic holography provides a powerful means to increase spatial resolution from electrode array data with careful choice of spatial filters and distance to reconstruction plane. More detailed approaches may provide the ability to volumetrically reconstruct activity patterns on neuronal tissue, but the ability to extract vectored data with the method presented already permits the study of dynamic causal interactions without bias from any prior assumptions on anatomical connectivity. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

An integrated multichannel neural recording analog front-end ASIC with area-efficient driven right leg circuit.

PubMed

Tao Tang; Wang Ling Goh; Lei Yao; Jia Hao Cheong; Yuan Gao

2017-07-01

This paper describes an integrated multichannel neural recording analog front end (AFE) with a novel area-efficient driven right leg (DRL) circuit to improve the system common mode rejection ratio (CMRR). The proposed AFE consists of an AC-coupled low-noise programmable-gain amplifier, an area-efficient DRL block and a 10-bit SAR ADC. Compared to conventional DRL circuit, the proposed capacitor-less DRL design achieves 90% chip area reduction with enhanced CMRR performance, making it ideal for multichannel biomedical recording applications. The AFE circuit has been designed in a standard 0.18-μm CMOS process. Post-layout simulation results show that the AFE provides two gain settings of 54dB/60dB while consuming 1 μA per channel under a supply voltage of 1 V. The input-referred noise of the AFE integrated from 1 Hz to 10k Hz is only 4 μVrms and the CMRR is 110 dB.

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

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.

Robust spike sorting of retinal ganglion cells tuned to spot stimuli.

PubMed

Ghahari, Alireza; Badea, Tudor C

2016-08-01

We propose an automatic spike sorting approach for the data recorded from a microelectrode array during visual stimulation of wild type retinas with tiled spot stimuli. The approach first detects individual spikes per electrode by their signature local minima. With the mixture probability distribution of the local minima estimated afterwards, it applies a minimum-squared-error clustering algorithm to sort the spikes into different clusters. A template waveform for each cluster per electrode is defined, and a number of reliability tests are performed on it and its corresponding spikes. Finally, a divisive hierarchical clustering algorithm is used to deal with the correlated templates per cluster type across all the electrodes. According to the measures of performance of the spike sorting approach, it is robust even in the cases of recordings with low signal-to-noise ratio.

Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation

PubMed Central

Paulk, Angelique C.; Zhou, Yanqiong; Stratton, Peter; Liu, Li

2013-01-01

Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel “whole brain” readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior. PMID:23864378

Nanostructured cavity devices for extracellular stimulation of HL-1 cells

NASA Astrophysics Data System (ADS)

Czeschik, Anna; Rinklin, Philipp; Derra, Ulrike; Ullmann, Sabrina; Holik, Peter; Steltenkamp, Siegfried; Offenhäusser, Andreas; Wolfrum, Bernhard

2015-05-01

Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network.Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network. Electronic supplementary information (ESI) available: Comparison of non-filtered and Savitzky-Golay filtered action potential recordings, electrical signals and corresponding optical signals. See DOI: 10.1039/c5nr01690h

77 FR 60721 - Certain Semiconductor Integrated Circuit Devices and Products Containing Same; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-04

... Circuit Devices and Products Containing Same; Notice of Commission Determination Not To Review an Initial... public record for this investigation may be viewed on the Commission's electronic docket (EDIS) at http... certain semiconductor integrated circuit devices and products containing same by reason of infringement of...

47 CFR 12.4 - Reliability of covered 911 service providers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... electronic records, as long as they reflect whether critical 911 circuits are physically diverse. (7... calls and associated number or location information to the appropriate PSAP. (5) Critical 911 circuits... calls to the PSAP(s). Critical 911 circuits also include ALI and ANI facilities that originate at the...

REPERTOIRE OF MESOSCOPIC CORTICAL ACTIVITY IS NOT REDUCED DURING ANESTHESIA

PubMed Central

HUDETZ, ANTHONY G.; VIZUETE, JEANNETTE A.; PILLAY, SIVESHIGAN; MASHOUR, GEORGE A.

2016-01-01

Consciousness has been linked to the repertoire of brain states at various spatiotemporal scales. Anesthesia is thought to modify consciousness by altering information integration in cortical and thalamocortical circuits. At a mesoscopic scale, neuronal populations in the cortex form synchronized ensembles whose characteristics are presumably state-dependent but this has not been rigorously tested. In this study, spontaneous neuronal activity was recorded with 64-contact microelectrode arrays in primary visual cortex of chronically instrumented, unrestrained rats under stepwise decreasing levels of desflurane anesthesia (8%, 6%, 4%, and 2% inhaled concentrations) and wakefulness (0% concentration). Negative phases of the local field potentials formed compact, spatially contiguous activity patterns (CAPs) that were not due to chance. The number of CAPs was 120% higher in wakefulness and deep anesthesia associated with burst-suppression than at intermediate levels of consciousness. The frequency distribution of CAP sizes followed a power–law with slope −1.5 in relatively deep anesthesia (8–6%) but deviated from that at the lighter levels. Temporal variance and entropy of CAP sizes were lowest in wakefulness (76% and 24% lower at 0% than at 8% desflurane, respectively) but changed little during recovery of consciousness. CAPs categorized by K-means clustering were conserved at all anesthesia levels and wakefulness, although their proportion changed in a state-dependent manner. These observations yield new knowledge about the dynamic landscape of ongoing population activity in sensory cortex at graded levels of anesthesia. The repertoire of population activity and self-organized criticality at the mesoscopic scale do not appear to contribute to anesthetic suppression of consciousness, which may instead depend on large-scale effects, more subtle dynamic properties, or changes outside of primary sensory cortex. PMID:27751957

Repertoire of mesoscopic cortical activity is not reduced during anesthesia.

PubMed

Hudetz, Anthony G; Vizuete, Jeannette A; Pillay, Siveshigan; Mashour, George A

2016-12-17

Consciousness has been linked to the repertoire of brain states at various spatiotemporal scales. Anesthesia is thought to modify consciousness by altering information integration in cortical and thalamocortical circuits. At a mesoscopic scale, neuronal populations in the cortex form synchronized ensembles whose characteristics are presumably state-dependent but this has not been rigorously tested. In this study, spontaneous neuronal activity was recorded with 64-contact microelectrode arrays in primary visual cortex of chronically instrumented, unrestrained rats under stepwise decreasing levels of desflurane anesthesia (8%, 6%, 4%, and 2% inhaled concentrations) and wakefulness (0% concentration). Negative phases of the local field potentials formed compact, spatially contiguous activity patterns (CAPs) that were not due to chance. The number of CAPs was 120% higher in wakefulness and deep anesthesia associated with burst-suppression than at intermediate levels of consciousness. The frequency distribution of CAP sizes followed a power-law with slope -1.5 in relatively deep anesthesia (8-6%) but deviated from that at the lighter levels. Temporal variance and entropy of CAP sizes were lowest in wakefulness (76% and 24% lower at 0% than at 8% desflurane, respectively) but changed little during recovery of consciousness. CAPs categorized by K-means clustering were conserved at all anesthesia levels and wakefulness, although their proportion changed in a state-dependent manner. These observations yield new knowledge about the dynamic landscape of ongoing population activity in sensory cortex at graded levels of anesthesia. The repertoire of population activity and self-organized criticality at the mesoscopic scale do not appear to contribute to anesthetic suppression of consciousness, which may instead depend on large-scale effects, more subtle dynamic properties, or changes outside of primary sensory cortex. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Micromolded PDMS planar electrode allows patch clamp electrical recordings from cells.

PubMed

Klemic, Kathryn G; Klemic, James F; Reed, Mark A; Sigworth, Fred J

2002-06-01

The patch clamp method measures membrane currents at very high resolution when a high-resistance 'gigaseal' is established between the glass microelectrode and the cell membrane (Pflugers Arch. 391 (1981) 85; Neuron 8 (1992) 605). Here we describe the first use of the silicone elastomer, poly(dimethylsiloxane) (PDMS), for patch clamp electrodes. PDMS is an attractive material for patch clamp recordings. It has low dielectric loss and can be micromolded (Annu. Rev. Mat. Sci. 28 (1998) 153) into a shape that mimics the tip of the glass micropipette. Also, the surface chemistry of PDMS may be altered to mimic the hydrophilic nature of glass (J. Appl. Polym. Sci. 14 (1970) 2499; Annu. Rev. Mat. Sci. 28 (1998) 153), thereby allowing a high-resistance seal to a cell membrane. We present a planar electrode geometry consisting of a PDMS partition with a small aperture sealed between electrode and bath chambers. We demonstrate that a planar PDMS patch electrode, after oxidation of the elastomeric surface, permits patch clamp recording on Xenopus oocytes. Our results indicate the potential for high-throughput patch clamp recording with a planar array of PDMS electrodes.

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

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

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.

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

Integration of Optical Manipulation and Electrophysiological Tools to Modulate and Record Activity in Neural Networks

NASA Astrophysics Data System (ADS)

Difato, F.; Schibalsky, L.; Benfenati, F.; Blau, A.

2011-07-01

We present an optical system that combines IR (1064 nm) holographic optical tweezers with a sub-nanosecond-pulsed UV (355 nm) laser microdissector for the optical manipulation of single neurons and entire networks both on transparent and non-transparent substrates in vitro. The phase-modulated laser beam can illuminate the sample concurrently or independently from above or below assuring compatibility with different types of microelectrode array and patch-clamp electrophysiology. By combining electrophysiological and optical tools, neural activity in response to localized stimuli or injury can be studied and quantified at sub-cellular, cellular, and network level.

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.

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.

76 FR 58040 - Certain Coaxial Cable Connectors and Components Thereof and Products Containing Same; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

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Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-04

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Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-17

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Superconductor magnetic reading and writing heads

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

Barnes, F.S.; Dugas, M.P.

1990-11-20

This paper describes a head for interfacing with a magnetic recording media. It comprises: a member of magnetic material forming at least a portion of a magnetic flux circuit ending with a pole face surface in interfacing relation to the media for establishing a main pole in proximity to the media in the magnetic flux circuit, magnetically responsive means in magnetically coupled relation to the magnetic flux circuit, means encasing at least a portion of the external surfaces of the member with superconductive material except for the media interfacing portion of the pole face surface. The encasing means including superconductingmore » material substantially surrounding the magnetic flux circuit in proximity to the pole face surface, and means establishing an environment for the superconductive material at a temperature for maintaining the superconductive material in its superconductive state, whereby magnetic flux in the magnetic flux circuit associated with the encasing means is concentrated within the magnetic flux circuit while placement of the pole face surface in proximity to the recording media permits sensitive magnetic flux controlled information exchanges between the media and the head.« less

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.

Predictive lethal proarrhythmic risk evaluation using a closed-loop-circuit cell network with human induced pluripotent stem cells derived cardiomyocytes

NASA Astrophysics Data System (ADS)

Nomura, Fumimasa; Hattori, Akihiro; Terazono, Hideyuki; Kim, Hyonchol; Odaka, Masao; Sugio, Yoshihiro; Yasuda, Kenji

2016-06-01

For the prediction of lethal arrhythmia occurrence caused by abnormality of cell-to-cell conduction, we have developed a next-generation in vitro cell-to-cell conduction assay, i.e., a quasi in vivo assay, in which the change in spatial cell-to-cell conduction is quantitatively evaluated from the change in waveforms of the convoluted electrophysiological signals from lined-up cardiomyocytes on a single closed loop of a microelectrode of 1 mm diameter and 20 µm width in a cultivation chip. To evaluate the importance of the closed-loop arrangement of cardiomyocytes for prediction, we compared the change in waveforms of convoluted signals of the responses in the closed-loop circuit arrangement with that of the response of cardiomyocyte clusters using a typical human ether a go-go related gene (hERG) ion channel blocker, E-4031. The results showed that (1) waveform prolongation and fluctuation both in the closed loops and clusters increased depending on the E-4031 concentration increase. However, (2) only the waveform signals in closed loops showed an apparent temporal change in waveforms from ventricular tachycardia (VT) to ventricular fibrillation (VF), which is similar to the most typical cell-to-cell conductance abnormality. The results indicated the usefulness of convoluted waveform signals of a closed-loop cell network for acquiring reproducible results acquisition and more detailed temporal information on cell-to-cell conduction.

Patterned free-standing conductive nanofilms for ultraconformable circuits and smart interfaces.

PubMed

Greco, Francesco; Zucca, Alessandra; Taccola, Silvia; Mazzolai, Barbara; Mattoli, Virgilio

2013-10-09

A process is presented for the fabrication of patterned ultrathin free-standing conductive nanofilms based on an all-polymer bilayer structure composed of poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate) and poly(lactic acid) (PEDOT:PSS/PLA). Based on the strategy recently introduced by our group for producing large area free-standing nanofilms of conductive polymers with ultrahigh conformability, here an inkjet subtractive patterning technique was used, with localized overoxidation of PEDOT:PSS that caused the local irreversible loss of electrical conductivity. Different pattern geometries (e.g., interdigitated electrodes with various spacing, etc.) were tested for validating the proposed process. The fabrication of individually addressable microelectrodes and simple circuits on nanofilm having thickness ∼250 nm has been demonstrated. Using this strategy, mechanically robust, conformable ultrathin polymer films could be produced that can be released in water as free-standing nanofilms and/or collected on surfaces with arbitrary shapes, topography and compliance, including human skin. The patterned bilayer nanofilms were characterized as regards their morphology, thickness, topography, conductivity, and electrochemical behavior. In addition, the electrochemical switching of surface properties has been evaluated by means of contact angle measurements. These novel conductive materials can find use as ultrathin, conformable electronic devices and in many bioelectrical applications. Moreover, by exploiting the electrochemical properties of conducting polymers, they can act as responsive smart biointerfaces and in the field of conformable bioelectronics, for example, as electrodes on tissues or smart conductive substrates for cell culturing and stimulation.

C-FSCV: Compressive Fast-Scan Cyclic Voltammetry for Brain Dopamine Recording.

PubMed

Zamani, Hossein; Bahrami, Hamid Reza; Chalwadi, Preeti; Garris, Paul A; Mohseni, Pedram

2018-01-01

This paper presents a novel compressive sensing framework for recording brain dopamine levels with fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode. Termed compressive FSCV (C-FSCV), this approach compressively samples the measured total current in each FSCV scan and performs basic FSCV processing steps, e.g., background current averaging and subtraction, directly with compressed measurements. The resulting background-subtracted faradaic currents, which are shown to have a block-sparse representation in the discrete cosine transform domain, are next reconstructed from their compressively sampled counterparts with the block sparse Bayesian learning algorithm. Using a previously recorded dopamine dataset, consisting of electrically evoked signals recorded in the dorsal striatum of an anesthetized rat, the C-FSCV framework is shown to be efficacious in compressing and reconstructing brain dopamine dynamics and associated voltammograms with high fidelity (correlation coefficient, ), while achieving compression ratio, CR, values as high as ~ 5. Moreover, using another set of dopamine data recorded 5 minutes after administration of amphetamine (AMPH) to an ambulatory rat, C-FSCV once again compresses (CR = 5) and reconstructs the temporal pattern of dopamine release with high fidelity ( ), leading to a true-positive rate of 96.4% in detecting AMPH-induced dopamine transients.

Effects of cell volume changes on membrane ionic permeabilities and sodium transport in frog skin (Rana ridibunda).

PubMed

Costa, P M; Fernandes, P L; Ferreira, H G; Ferreira, K T; Giraldez, F

1987-12-01

1. Membrane potential and conductances and short-circuit current were continuously measured with microelectrodes and conventional electrophysiological techniques in a stripped preparation of frog skin epithelium. The effects of the removal of chloride or sodium ions and the concentration or dilution of the serosal (inner) bathing solution were studied. 2. Chloride- or sodium-free solutions produced a cell depolarization of about 30 mV in parallel with a fall in the short-circuit current. Mucosal and serosal membrane conductances both decreased and the sodium permeability of the mucosal barrier was calculated to fall to about one-half its value in standard Ringer solution. The observed decrease in the short-circuit current is probably related to the combined effect of the decrease in sodium permeability and the decrease in the driving force across the mucosal membrane. 3. The removal of chloride or sodium ions reduced the depolarization caused by serosal perfusion with high-potassium solutions (50 mM-KCl). The ratio of the change in cell membrane potential under short-circuit conditions to the change in the potassium equilibrium potential (delta Ec(s.c.)/delta EK), was 0.59 in standard Ringer solution and 0.26 and 0.24 after the removal of chloride or sodium respectively. The depolarizing effect of barium-containing solutions (2 mM-BaCl2) was also markedly reduced in chloride- or sodium-free solutions, suggesting a decrease of the potassium selectivity of the serosal membrane in these conditions. 4. Increasing the osmolality of the serosal bathing solution produced similar effects, i.e. cell depolarization, fall in the short-circuit current and membrane conductances and reduction of the depolarizing effect of high-potassium and barium solutions. On the contrary, dilution of the serosal bath produced the opposite effects, consistent with an increase in the serosal permeability to potassium. 5. The effects of chloride- or sodium-free solutions were reversed by the dilution of the serosal bath. Cells repolarized when exposed to low-osmolality solutions after being in the absence of serosal chloride or sodium. The repolarization ran in parallel with the restoration of the short-circuit current and the potassium selectivity of the serosal membrane. 6. The results show that the effects produced by the removal of sodium or chloride ions from the serosal bathing solution are most probably mediated by a reduction in cell volume. Cell volume changes would lead to changes in the serosal membrane selectivity to potassium and thus to changes in cell membrane potential and sodium transport.(ABSTRACT TRUNCATED AT 400 WORDS)

Circuit Models and Experimental Noise Measurements of Micropipette Amplifiers for Extracellular Neural Recordings from Live Animals

PubMed Central

Chen, Chang Hao; Pun, Sio Hang; Mak, Peng Un; Vai, Mang I; Klug, Achim; Lei, Tim C.

2014-01-01

Glass micropipettes are widely used to record neural activity from single neurons or clusters of neurons extracellularly in live animals. However, to date, there has been no comprehensive study of noise in extracellular recordings with glass micropipettes. The purpose of this work was to assess various noise sources that affect extracellular recordings and to create model systems in which novel micropipette neural amplifier designs can be tested. An equivalent circuit of the glass micropipette and the noise model of this circuit, which accurately describe the various noise sources involved in extracellular recordings, have been developed. Measurement schemes using dead brain tissue as well as extracellular recordings from neurons in the inferior colliculus, an auditory brain nucleus of an anesthetized gerbil, were used to characterize noise performance and amplification efficacy of the proposed micropipette neural amplifier. According to our model, the major noise sources which influence the signal to noise ratio are the intrinsic noise of the neural amplifier and the thermal noise from distributed pipette resistance. These two types of noise were calculated and measured and were shown to be the dominating sources of background noise for in vivo experiments. PMID:25133158

A compact nanopower low output impedance CMOS operational amplifier for wireless intraocular pressure recordings.

PubMed

Dresher, Russell P; Irazoqui, Pedro P

2007-01-01

Wireless sensing has shown potential benefits for the continuous-time measurement of physiological data. One such application is the recording of intraocular pressure (IOP) for patients with glaucoma. Ultra-low-power circuits facilitate the use of inductively-coupled power for implantable wireless systems. Compact circuit size is also desirable for implantable systems. As a first step towards the realization of such circuits, we have designed a compact, ultra-low-power operational amplifier which can be used to record IOP. This paper presents the measured results of a CMOS operational amplifier that can be incorporated with a wireless IOP monitoring system or other low-power application. It has a power consumption of 736 nW, chip area of 0.023 mm2, and output impedance of 69 Omega to drive low-impedance loads.

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.

Carotid chemoreceptors tune breathing via multipath routing: reticular chain and loop operations supported by parallel spike train correlations.

PubMed

Morris, Kendall F; Nuding, Sarah C; Segers, Lauren S; Iceman, Kimberly E; O'Connor, Russell; Dean, Jay B; Ott, Mackenzie M; Alencar, Pierina A; Shuman, Dale; Horton, Kofi-Kermit; Taylor-Clark, Thomas E; Bolser, Donald C; Lindsey, Bruce G

2018-02-01

We tested the hypothesis that carotid chemoreceptors tune breathing through parallel circuit paths that target distinct elements of an inspiratory neuron chain in the ventral respiratory column (VRC). Microelectrode arrays were used to monitor neuronal spike trains simultaneously in the VRC, peri-nucleus tractus solitarius (p-NTS)-medial medulla, the dorsal parafacial region of the lateral tegmental field (FTL-pF), and medullary raphe nuclei together with phrenic nerve activity during selective stimulation of carotid chemoreceptors or transient hypoxia in 19 decerebrate, neuromuscularly blocked, and artificially ventilated cats. Of 994 neurons tested, 56% had a significant change in firing rate. A total of 33,422 cell pairs were evaluated for signs of functional interaction; 63% of chemoresponsive neurons were elements of at least one pair with correlational signatures indicative of paucisynaptic relationships. We detected evidence for postinspiratory neuron inhibition of rostral VRC I-Driver (pre-Bötzinger) neurons, an interaction predicted to modulate breathing frequency, and for reciprocal excitation between chemoresponsive p-NTS neurons and more downstream VRC inspiratory neurons for control of breathing depth. Chemoresponsive pericolumnar tonic expiratory neurons, proposed to amplify inspiratory drive by disinhibition, were correlationally linked to afferent and efferent "chains" of chemoresponsive neurons extending to all monitored regions. The chains included coordinated clusters of chemoresponsive FTL-pF neurons with functional links to widespread medullary sites involved in the control of breathing. The results support long-standing concepts on brain stem network architecture and a circuit model for peripheral chemoreceptor modulation of breathing with multiple circuit loops and chains tuned by tegmental field neurons with quasi-periodic discharge patterns. NEW & NOTEWORTHY We tested the long-standing hypothesis that carotid chemoreceptors tune the frequency and depth of breathing through parallel circuit operations targeting the ventral respiratory column. Responses to stimulation of the chemoreceptors and identified functional connectivity support differential tuning of inspiratory neuron burst duration and firing rate and a model of brain stem network architecture incorporating tonic expiratory "hub" neurons regulated by convergent neuronal chains and loops through rostral lateral tegmental field neurons with quasi-periodic discharge patterns.

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.

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.

MEAs and 3D nanoelectrodes: electrodeposition as tool for a precisely controlled nanofabrication.

PubMed

Weidlich, Sabrina; Krause, Kay J; Schnitker, Jan; Wolfrum, Bernhard; Offenhäusser, Andreas

2017-01-31

Microelectrode arrays (MEAs) are gaining increasing importance for the investigation of signaling processes between electrogenic cells. However, efficient cell-chip coupling for robust and long-term electrophysiological recording and stimulation still remains a challenge. A possible approach for the improvement of the cell-electrode contact is the utilization of three-dimensional structures. In recent years, various 3D electrode geometries have been developed, but we are still lacking a fabrication approach that enables the formation of different 3D structures on a single chip in a controlled manner. This, however, is needed to enable a direct and reliable comparison of the recording capabilities of the different structures. Here, we present a method for a precisely controlled deposition of nanoelectrodes, enabling the fabrication of multiple, well-defined types of structures on our 64 electrode MEAs towards a rapid-prototyping approach to 3D electrodes.

3D silicon neural probe with integrated optical fibers for optogenetic modulation.

PubMed

Kim, Eric G R; Tu, Hongen; Luo, Hao; Liu, Bin; Bao, Shaowen; Zhang, Jinsheng; Xu, Yong

2015-07-21

Optogenetics is a powerful modality for neural modulation that can be useful for a wide array of biomedical studies. Penetrating microelectrode arrays provide a means of recording neural signals with high spatial resolution. It is highly desirable to integrate optics with neural probes to allow for functional study of neural tissue by optogenetics. In this paper, we report the development of a novel 3D neural probe coupled simply and robustly to optical fibers using a hollow parylene tube structure. The device shanks are hollow tubes with rigid silicon tips, allowing the insertion and encasement of optical fibers within the shanks. The position of the fiber tip can be precisely controlled relative to the electrodes on the shank by inherent design features. Preliminary in vivo rat studies indicate that these devices are capable of optogenetic modulation simultaneously with 3D neural signal recording.

Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus.

PubMed

Khodagholy, Dion; Gelinas, Jennifer N; Buzsáki, György

2017-10-20

Consolidation of declarative memories requires hippocampal-neocortical communication. Although experimental evidence supports the role of sharp-wave ripples in transferring hippocampal information to the neocortex, the exact cortical destinations and the physiological mechanisms of such transfer are not known. We used a conducting polymer-based conformable microelectrode array (NeuroGrid) to record local field potentials and neural spiking across the dorsal cortical surface of the rat brain, combined with silicon probe recordings in the hippocampus, to identify candidate physiological patterns. Parietal, midline, and prefrontal, but not primary cortical areas, displayed localized ripple (100 to 150 hertz) oscillations during sleep, concurrent with hippocampal ripples. Coupling between hippocampal and neocortical ripples was strengthened during sleep following learning. These findings suggest that ripple-ripple coupling supports hippocampal-association cortical transfer of memory traces. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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.

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

Optical coherence tomography and optical coherence domain reflectometry for deep brain stimulation probe guidance

NASA Astrophysics Data System (ADS)

Jeon, Sung W.; Shure, Mark A.; Baker, Kenneth B.; Chahlavi, Ali; Hatoum, Nagi; Turbay, Massud; Rollins, Andrew M.; Rezai, Ali R.; Huang, David

2005-04-01

Deep Brain Stimulation (DBS) is FDA-approved for the treatment of Parkinson's disease and essential tremor. Currently, placement of DBS leads is guided through a combination of anatomical targeting and intraoperative microelectrode recordings. The physiological mapping process requires several hours, and each pass of the microelectrode into the brain increases the risk of hemorrhage. Optical Coherence Domain Reflectometry (OCDR) in combination with current methodologies could reduce surgical time and increase accuracy and safety by providing data on structures some distance ahead of the probe. For this preliminary study, we scanned a rat brain in vitro using polarization-insensitive Optical Coherence Tomography (OCT). For accurate measurement of intensity and attenuation, polarization effects arising from tissue birefringence are removed by polarization diversity detection. A fresh rat brain was sectioned along the coronal plane and immersed in a 5 mm cuvette with saline solution. OCT images from a 1294 nm light source showed depth profiles up to 2 mm. Light intensity and attenuation rate distinguished various tissue structures such as hippocampus, cortex, external capsule, internal capsule, and optic tract. Attenuation coefficient is determined by linear fitting of the single scattering regime in averaged A-scans where Beer"s law is applicable. Histology showed very good correlation with OCT images. From the preliminary study using OCT, we conclude that OCDR is a promising approach for guiding DBS probe placement.

Editor's highlight: Evaluation of a Microelectrode Array-based ...

EPA Pesticide Factsheets

Thousands of compounds in the environment have not been characterized for developmental neurotoxicity (DNT) hazard. To address this issue, methods to screen compounds rapidly for DNT hazard evaluation are necessary and are being developed for key neurodevelopmental processes. In order to develop an assay for network formation, the current study evaluated effects of a training set of chemicals on network ontogeny by measuring spontaneous electrical activity in neural networks grown on microelectrode arrays (MEA). Rat (0-24 h old) primary cortical cells were plated in 48 well MEA plates and exposed to six compounds: acetaminophen, bisindolylmaleimide-1 (Bis-1), domoic acid, mevastatin, sodium orthovanadate, and loperamide for a period of 12 days. Spontaneous network activity was recorded on days 2, 5, 7, 9, and 12 and viability was assessed using the Cell Titer Blue® assay on day 12. Network activity (e.g. mean firing rate (MFR), burst rate (BR), etc), increased between days 5 and 12. Random Forest analysis indicated that across all compounds and times, temporal correlation of firing patterns (r), MFR, BR, #of active electrodes and % of spikes in a burst were the most influential parameters in separating control from treated wells. All compounds except acetaminophen (≤ 30 µM) caused concentration-related effects on one or more of these parameters. Domoic acid and sodium orthovanadate altered several of these parameters in the absence of cytotoxicity. Although

Visual Tuning Properties of Genetically Identified Layer 2/3 Neuronal Types in the Primary Visual Cortex of Cre-Transgenic Mice

PubMed Central

Zariwala, Hatim A.; Madisen, Linda; Ahrens, Kurt F.; Bernard, Amy; Lein, Edward S.; Jones, Allan R.; Zeng, Hongkui

2011-01-01

The putative excitatory and inhibitory cell classes within the mouse primary visual cortex V1 have different functional properties as studied using recording microelectrode. Excitatory neurons show high selectivity for the orientation angle of moving gratings while the putative inhibitory neurons show poor selectivity. However, the study of selectivity of the genetically identified interneurons and their subtypes remain controversial. Here we use novel Cre-driver and reporter mice to identify genetic subpopulations in vivo for two-photon calcium dye imaging: Wfs1(+)/Gad1(−) mice that labels layer 2/3 excitatory cell population and Pvalb(+)/Gad1(+) mice that labels a genetic subpopulation of inhibitory neurons. The cells in both mice were identically labeled with a tdTomato protein, visible in vivo, using a Cre-reporter line. We found that the Wfs1(+) cells exhibited visual tuning properties comparable to the excitatory population, i.e., high selectivity and tuning to the angle, direction, and spatial frequency of oriented moving gratings. The functional tuning of Pvalb(+) neurons was consistent with previously reported narrow-spiking interneurons in microelectrode studies, exhibiting poorer selectivity than the excitatory neurons. This study demonstrates the utility of Cre-transgenic mouse technology in selective targeting of subpopulations of neurons and makes them amenable to structural, functional, and connectivity studies. PMID:21283555

A Framework for the Comparative Assessment of Neuronal Spike Sorting Algorithms towards More Accurate Off-Line and On-Line Microelectrode Arrays Data Analysis.

PubMed

Regalia, Giulia; Coelli, Stefania; Biffi, Emilia; Ferrigno, Giancarlo; Pedrocchi, Alessandra

2016-01-01

Neuronal spike sorting algorithms are designed to retrieve neuronal network activity on a single-cell level from extracellular multiunit recordings with Microelectrode Arrays (MEAs). In typical analysis of MEA data, one spike sorting algorithm is applied indiscriminately to all electrode signals. However, this approach neglects the dependency of algorithms' performances on the neuronal signals properties at each channel, which require data-centric methods. Moreover, sorting is commonly performed off-line, which is time and memory consuming and prevents researchers from having an immediate glance at ongoing experiments. The aim of this work is to provide a versatile framework to support the evaluation and comparison of different spike classification algorithms suitable for both off-line and on-line analysis. We incorporated different spike sorting "building blocks" into a Matlab-based software, including 4 feature extraction methods, 3 feature clustering methods, and 1 template matching classifier. The framework was validated by applying different algorithms on simulated and real signals from neuronal cultures coupled to MEAs. Moreover, the system has been proven effective in running on-line analysis on a standard desktop computer, after the selection of the most suitable sorting methods. This work provides a useful and versatile instrument for a supported comparison of different options for spike sorting towards more accurate off-line and on-line MEA data analysis.

A Framework for the Comparative Assessment of Neuronal Spike Sorting Algorithms towards More Accurate Off-Line and On-Line Microelectrode Arrays Data Analysis

PubMed Central

Pedrocchi, Alessandra

2016-01-01

Neuronal spike sorting algorithms are designed to retrieve neuronal network activity on a single-cell level from extracellular multiunit recordings with Microelectrode Arrays (MEAs). In typical analysis of MEA data, one spike sorting algorithm is applied indiscriminately to all electrode signals. However, this approach neglects the dependency of algorithms' performances on the neuronal signals properties at each channel, which require data-centric methods. Moreover, sorting is commonly performed off-line, which is time and memory consuming and prevents researchers from having an immediate glance at ongoing experiments. The aim of this work is to provide a versatile framework to support the evaluation and comparison of different spike classification algorithms suitable for both off-line and on-line analysis. We incorporated different spike sorting “building blocks” into a Matlab-based software, including 4 feature extraction methods, 3 feature clustering methods, and 1 template matching classifier. The framework was validated by applying different algorithms on simulated and real signals from neuronal cultures coupled to MEAs. Moreover, the system has been proven effective in running on-line analysis on a standard desktop computer, after the selection of the most suitable sorting methods. This work provides a useful and versatile instrument for a supported comparison of different options for spike sorting towards more accurate off-line and on-line MEA data analysis. PMID:27239191

Persistent increase in oxygen consumption and impaired neurovascular coupling after spreading depression in rat neocortex.

PubMed

Piilgaard, Henning; Lauritzen, Martin

2009-09-01

Cortical spreading depression (CSD) is associated with a dramatic failure of brain ion homeostasis and increased energy metabolism. There is strong clinical and experimental evidence to suggest that CSD is the mechanism of migraine, and involved in progressive neuronal injury in stroke and head trauma. Here we tested the hypothesis that single episodes of CSD induced acute hypoxia, and prolonged impairment of neurovascular and neurometabolic coupling. Cortical spreading depression was induced in rat frontal cortex, whereas cortical electrical activity and local field potentials (LFPs) were recorded by glass microelectrodes, cerebral blood flow (CBF) by laser-Doppler flowmetry, and tissue oxygen tension (tpO(2)) with polarographic microelectrodes. Cortical spreading depression increased cerebral metabolic rate of oxygen (CMRO(2)) by 71%+/-6.7% and CBF by 238%+/-48.1% for 1 to 2 mins. For the following 2 h, basal tpO(2) and CBF were reduced whereas basal CMRO(2) was persistently elevated by 8.1%+/-2.9%. In addition, within first hour after CSD we found impaired neurovascular coupling (LFP versus CBF), whereas neurometabolic coupling (LFP versus CMRO(2)) remained unaffected. Impaired neurovascular coupling was explained by both reduced vascular reactivity and suppressed function of cortical inhibitory interneurons. The protracted effects of CSD on basal CMRO(2) and neurovascular coupling may contribute to cellular dysfunction in patients with migraine and acutely injured cerebral cortex.

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.

On-line observation of cell growth in a three-dimensional matrix on surface-modified microelectrode arrays.

PubMed

Lin, Shu-Ping; Kyriakides, Themis R; Chen, Jia-Jin J

2009-06-01

Despite many successful applications of microelectrode arrays (MEAs), typical two-dimensional in-vitro cultures do not project the full scale of the cell growth environment in the three-dimensional (3D) in-vivo setting. This study aims to on-line monitor in-vitro cell growth in a 3D matrix on the surface-modified MEAs with a dynamic perfusion culture system. A 3D matrix consisting of poly(ethylene glycol) hydrogel supplemented with poly-D-lysine was subsequently synthesized in situ on the self-assembled monolayer modified MEAs. FTIR spectrum analysis revealed a peak at 2100 cm(-1) due to the degradation of the structure of the 3D matrix. After 2 wks, microscopic examination revealed that the non-degraded area was around 1500 microm(2) and provided enough space for cell growth. Fluorescence microscopy revealed that the degraded 3D matrix was non-cytotoxic allowing the growth of NIH3T3 fibroblasts and cortical neurons in vitro. Time-course changes of total impedance including resistance and reactance were recorded for 8 days to evaluate the cell growth in the 3D matrix on the MEA. A consistent trend reflecting changes of reactance and total impedance was observed. These in-vitro assays demonstrate that our 3D matrix can construct a biomimetic system for cell growth and analysis of cell surface interactions.

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.

Membrane currents underlying activity in frog sinus venosus

PubMed Central

Brown, Hilary F.; Giles, Wayne; Noble, Susan J.

1977-01-01

1. The spontaneous electrical activity of small strips of muscle from the sinus venosus region of the heart of Rana catesbeiana was investigated using the double sucrose gap technique. The voltage clamp was used to record the ionic currents underlying the pace-maker depolarization and the action potential. 2. The records of spontaneous electrical activity are very similar to those obtained from the sinus venosus using micro-electrodes. Moreover, the pace-maker activity is almost completely insensitive to tetrodotoxin (TTX) at 2·0 × 10-6 g/ml., which suggests that the pace-maker responses can be classified as primary, as opposed to follower pacing. 3. In response to short rectangular depolarizing voltage clamp pulses, only one inward current is activated. This current is almost completely insensitive to TTX but can be blocked by manganese ions. It appears, therefore, to be equivalent to the slow inward (Ca2+/Na+) current, Isi, of other cardiac tissues. The threshold for Isi is near to the maximum diastolic potential, indicating that it must be activated during the pace-maker depolarization. 4. Interruption of the normal pace-maker depolarization by rapid activation of the voltage clamp circuit reveals the time-dependent decay of outward current. This current reverses between -75 and -90 mV and, therefore, is probably carried mainly by potassium ions. 5. Outward current decay is not a simple exponential, and Hodgkin—Huxley analysis suggests that two distinct components of outward current may be present. One of these is activated in the potential range of the pace-maker depolarization and the other at more positive potentials. Both outward currents reach full, steady-state activation at about zero mV, i.e. within the `plateau' range of the sinus action potential. 6. These results are compared with other recently published voltage clamp data from the rabbit sino—atrial node. 7. A hypothesis for the generation of pace-maker activity is presented which involves (i) decay of outward current and (ii) activation of the slow inward current, Isi. PMID:303699

Magnetic Recording.

ERIC Educational Resources Information Center

Lowman, Charles E.

A guide to the technology of magnetic recorders used in such fields as audio recording, broadcast and closed-circuit television, instrumentation recording, and computer data systems is presented. Included are discussions of applications, advantages, and limitations of magnetic recording, its basic principles and theory of operation, and its…

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.

Validation diagnostics for defective thermocouple circuits

NASA Astrophysics Data System (ADS)

Reed, R. P.

Thermocouples, properly used under favorable conditions, can measure temperature with an accepted tolerance. However, when improperly applied or exposed to hostile mechanical, chemical, thermal, or radiation environments, they often fail without the error being evident in the temperature record. Conversely, features that appear to be unreasonable in temperature records can be authentic. When hidden failure occurs during measurement, deliberate recording of supplementary information is necessary to distinguish valid from faulty data. Loop resistance change, circuit isolation, isolated noise potential, and other measures can reveal symptoms of developing defects. Monitored continually along with temperature, they can reveal the occurrence, location, and natures of damage incurred during measurement. Special multiterminal branched thermocouple circuits and combinatorial multiplex switching allow detection of dc measurement noise and decalibration. Symptoms of insidious failure, often consequential, are illustrated by examples from field experience in measuring temperature of a propagating retorting front in underground coal gasification.

Micropower circuits for bidirectional wireless telemetry in neural recording applications.

PubMed

Neihart, Nathan M; Harrison, Reid R

2005-11-01

State-of-the art neural recording systems require electronics allowing for transcutaneous, bidirectional data transfer. As these circuits will be implanted near the brain, they must be small and low power. We have developed micropower integrated circuits for recovering clock and data signals over a transcutaneous power link. The data recovery circuit produces a digital data signal from an ac power waveform that has been amplitude modulated. We have also developed an FM transmitter with the lowest power dissipation reported for biosignal telemetry. The FM transmitter consists of a low-noise biopotential amplifier and a voltage controlled oscillator used to transmit amplified neural signals at a frequency near 433 MHz. All circuits were fabricated in a standard 0.5-microm CMOS VLSI process. The resulting chip is powered through a wireless inductive link. The power consumption of the clock and data recovery circuits is measured to be 129 microW; the power consumption of the transmitter is measured to be 465 microW when using an external surface mount inductor. Using a parasitic antenna less than 2 mm long, a received power level was measured to be -59.73 dBm at a distance of one meter.

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

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).

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

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.

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.

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

Synthetic Analog and Digital Circuits for Cellular Computation and Memory

PubMed Central

Purcell, Oliver; Lu, Timothy K.

2014-01-01

Biological computation is a major area of focus in synthetic biology because it has the potential to enable a wide range of applications. Synthetic biologists have applied engineering concepts to biological systems in order to construct progressively more complex gene circuits capable of processing information in living cells. Here, we review the current state of computational genetic circuits and describe artificial gene circuits that perform digital and analog computation. We then discuss recent progress in designing gene circuits that exhibit memory, and how memory and computation have been integrated to yield more complex systems that can both process and record information. Finally, we suggest new directions for engineering biological circuits capable of computation. PMID:24794536

[Serial change of perilymphatic potassium ion concentration in the scala tympani after introducing KCl-solution into the guinea pigs' tympanic cavity].

PubMed

Ikeno, K

1990-09-01

Characteristic nystagmus similar to the Meniere's attack could be observed after introducing KCl solution into the tympanic cavity of guinea pigs. To confirm the fact that this nystagmus was provoked by the high perilymphatic potassium ion concentration, the K+ activity of perilymph was recorded serially through the K+ specific microelectrode inserted into the scala tympani. The rapid increment of K+ activity reached maximum at 120 minutes after introducing KCl solution, and then it decreased gradually to a half of the maximum activity. However, such change of perilymphatic potassium ion concentration was not observed by introducing sucrose solution as control.

Microfluidic device for unidirectional axon growth

NASA Astrophysics Data System (ADS)

Malishev, E.; Pimashkin, A.; Gladkov, A.; Pigareva, Y.; Bukatin, A.; Kazantsev, V.; Mukhina, I.; Dubina, M.

2015-11-01

In order to better understand the communication and connectivity development of neuron networks, we designed microfluidic devices with several chambers for growing dissociated neuronal cultures from mice fetal hippocampus (E18). The chambers were connected with microchannels providing unidirectional axonal growth between “Source” and “Target” neural sub-networks. Experiments were performed in a hippocampal cultures plated in a poly-dimethylsiloxane (PDMS) microfluidic chip, aligned with a 60 microelectrode array (MEA). Axonal growth through microchannels was observed with brightfield, phase-contrast and fluorescence microscopy, and after 7 days in vitro electrical activity was recorded. Visual inspection and spike propagation analysis showed the predominant axonal growth in microchannels in a direction from “Source” to “Target”.

Non ictal onset zone: A window to ictal dynamics.

PubMed

Afra, Pegah; Hanrahan, Sara J; Kellis, Spencer Sterling; House, Paul

2017-01-01

The focal and network concepts of epilepsy present different aspects of electroclinical phenomenon of seizures. Here, we present a 23-year-old man undergoing surgical evaluation with left fronto-temporal electrocorticography (ECoG) and microelectrode-array (MEA) in the middle temporal gyrus (MTG). We compare action-potential (AP) and local field potentials (LFP) recorded from MEA with ECoG. Seizure onset in the mesial-temporal lobe was characterized by changes in the pattern of AP-firing without clear changes in LFP or ECoG in MTG. This suggests simultaneous analysis of neuronal activity in differing spatial scales and frequency ranges provide complementary insights into how focal and network neurophysiological activity contribute to ictal activity.

Digital micromirror based near-infrared illumination system for plasmonic photothermal neuromodulation

PubMed Central

Jung, Hyunjun; Kang, Hongki; Nam, Yoonkey

2017-01-01

Light-mediated neuromodulation techniques provide great advantages to investigate neuroscience due to its high spatial and temporal resolution. To generate a spatial pattern of neural activity, it is necessary to develop a system for patterned-light illumination to a specific area. Digital micromirror device (DMD) based patterned illumination system have been used for neuromodulation due to its simple configuration and design flexibility. In this paper, we developed a patterned near-infrared (NIR) illumination system for region specific photothermal manipulation of neural activity using NIR-sensitive plasmonic gold nanorods (GNRs). The proposed system had high power transmission efficiency for delivering power density up to 19 W/mm2. We used a GNR-coated microelectrode array (MEA) to perform biological experiments using E18 rat hippocampal neurons and showed that it was possible to inhibit neural spiking activity of specific area in neural circuits with the patterned NIR illumination. This patterned NIR illumination system can serve as a promising neuromodulation tool to investigate neuroscience in a wide range of physiological and clinical applications. PMID:28663912

Mapping Inhibitory Neuronal Circuits by Laser Scanning Photostimulation

PubMed Central

Ikrar, Taruna; Olivas, Nicholas D.; Shi, Yulin; Xu, Xiangmin

2011-01-01

Inhibitory neurons are crucial to cortical function. They comprise about 20% of the entire cortical neuronal population and can be further subdivided into diverse subtypes based on their immunochemical, morphological, and physiological properties1-4. Although previous research has revealed much about intrinsic properties of individual types of inhibitory neurons, knowledge about their local circuit connections is still relatively limited3,5,6. Given that each individual neuron's function is shaped by its excitatory and inhibitory synaptic input within cortical circuits, we have been using laser scanning photostimulation (LSPS) to map local circuit connections to specific inhibitory cell types. Compared to conventional electrical stimulation or glutamate puff stimulation, LSPS has unique advantages allowing for extensive mapping and quantitative analysis of local functional inputs to individually recorded neurons3,7-9. Laser photostimulation via glutamate uncaging selectively activates neurons perisomatically, without activating axons of passage or distal dendrites, which ensures a sub-laminar mapping resolution. The sensitivity and efficiency of LSPS for mapping inputs from many stimulation sites over a large region are well suited for cortical circuit analysis. Here we introduce the technique of LSPS combined with whole-cell patch clamping for local inhibitory circuit mapping. Targeted recordings of specific inhibitory cell types are facilitated by use of transgenic mice expressing green fluorescent proteins (GFP) in limited inhibitory neuron populations in the cortex3,10, which enables consistent sampling of the targeted cell types and unambiguous identification of the cell types recorded. As for LSPS mapping, we outline the system instrumentation, describe the experimental procedure and data acquisition, and present examples of circuit mapping in mouse primary somatosensory cortex. As illustrated in our experiments, caged glutamate is activated in a spatially restricted region of the brain slice by UV laser photolysis; simultaneous voltage-clamp recordings allow detection of photostimulation-evoked synaptic responses. Maps of either excitatory or inhibitory synaptic input to the targeted neuron are generated by scanning the laser beam to stimulate hundreds of potential presynaptic sites. Thus, LSPS enables the construction of detailed maps of synaptic inputs impinging onto specific types of inhibitory neurons through repeated experiments. Taken together, the photostimulation-based technique offers neuroscientists a powerful tool for determining the functional organization of local cortical circuits. PMID:22006064

Traveling Culture: Circuit Chautauqua in the Twentieth Century - The

Science.gov Websites

Libraries Archival Collections Records of the Redpath Chautauqua Related Links Essay: What Was Chautauqua spoken word recordings, and programs drawn from the Records of the Redpath Lyceum Bureau, the largest

Heterogeneous neuronal firing patterns during interictal epileptiform discharges in the human cortex

PubMed Central

Keller, Corey J.; Truccolo, Wilson; Gale, John T.; Eskandar, Emad; Thesen, Thomas; Carlson, Chad; Devinsky, Orrin; Kuzniecky, Ruben; Doyle, Werner K.; Madsen, Joseph R.; Schomer, Donald L.; Mehta, Ashesh D.; Brown, Emery N.; Hochberg, Leigh R.; Ulbert, István; Halgren, Eric

2010-01-01

Epileptic cortex is characterized by paroxysmal electrical discharges. Analysis of these interictal discharges typically manifests as spike–wave complexes on electroencephalography, and plays a critical role in diagnosing and treating epilepsy. Despite their fundamental importance, little is known about the neurophysiological mechanisms generating these events in human focal epilepsy. Using three different systems of microelectrodes, we recorded local field potentials and single-unit action potentials during interictal discharges in patients with medically intractable focal epilepsy undergoing diagnostic workup for localization of seizure foci. We studied 336 single units in 20 patients. Ten different cortical areas and the hippocampus, including regions both inside and outside the seizure focus, were sampled. In three of these patients, high density microelectrode arrays simultaneously recorded between 43 and 166 single units from a small (4 mm × 4 mm) patch of cortex. We examined how the firing rates of individual neurons changed during interictal discharges by determining whether the firing rate during the event was the same, above or below a median baseline firing rate estimated from interictal discharge-free periods (Kruskal–Wallis one-way analysis, P<0.05). Only 48% of the recorded units showed such a modulation in firing rate within 500 ms of the discharge. Units modulated during the discharge exhibited significantly higher baseline firing and bursting rates than unmodulated units. As expected, many units (27% of the modulated population) showed an increase in firing rate during the fast segment of the discharge (±35 ms from the peak of the discharge), while 50% showed a decrease during the slow wave. Notably, in direct contrast to predictions based on models of a pure paroxysmal depolarizing shift, 7.7% of modulated units recorded in or near the seizure focus showed a decrease in activity well ahead (0–300 ms) of the discharge onset, while 12.2% of units increased in activity in this period. No such pre-discharge changes were seen in regions well outside the seizure focus. In many recordings there was also a decrease in broadband field potential activity during this same pre-discharge period. The different patterns of interictal discharge-modulated firing were classified into more than 15 different categories. This heterogeneity in single unit activity was present within small cortical regions as well as inside and outside the seizure onset zone, suggesting that interictal epileptiform activity in patients with epilepsy is not a simple paroxysm of hypersynchronous excitatory activity, but rather represents an interplay of multiple distinct neuronal types within complex neuronal networks. PMID:20511283

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.

[Intranasal epitalon infusion modulates neuronal activity in the rat neocortex].

PubMed

Sibarov, D A; Vol'nova, A B; Frolov, D S; Nosdrachev, A D

2006-08-01

Properties of tetrapeptide epitalon (Ala-Glu-Asp-Gly) constructed on the basis of pineal peptide extract, have been studied. The intranasal infusions: a noninvasive way to deliver this peptide to CNS hypassing the blood-brain barrier, was used. The aim of the study is to estimate epitalon action on rat motor cortex spontaneous activity. Wistar male rats were anesthetized with urethane (1 g/kg). Extracellular unit recording was made using glass microelectrodes (1-2 MOhm). After recording of spontaneous activity (10-15 min), epitalon intranasal infusion (2 ng) was followed by 30-minute recording. Within a few minutes after the infusion, significant activation of neural activity was observed (2-2.5-fold higher frequency of neuronal spikes). Complex response consisting of several phases was identified in some recordings. The spikes frequency growth during 5 to 7 min (first phase) after the infusion was followed by the second (11-12 min) and the third (17-18 min) phases. An increase of neuronal spontaneous activity was conditioned by the higher frequency of already active units and by the involvement of previously silent cells. At least the first phase of epitalon action can be explained by direct action of the peptide on the cells of the motor cortex.

Molecular interfaces for plasmonic hot electron photovoltaics

NASA Astrophysics Data System (ADS)

Pelayo García de Arquer, F.; Mihi, Agustín; Konstantatos, Gerasimos

2015-01-01

The use of self-assembled monolayers (SAMs) to improve and tailor the photovoltaic performance of plasmonic hot-electron Schottky solar cells is presented. SAMs allow the simultaneous control of open-circuit voltage, hot-electron injection and short-circuit current. To that end, a plurality of molecule structural parameters can be adjusted: SAM molecule's length can be adjusted to control plasmonic hot electron injection. Modifying SAMs dipole moment allows for a precise tuning of the open-circuit voltage. The functionalization of the SAM can also be selected to modify short-circuit current. This allows the simultaneous achievement of high open-circuit voltages (0.56 V) and fill-factors (0.58), IPCE above 5% at the plasmon resonance and maximum power-conversion efficiencies of 0.11%, record for this class of devices.The use of self-assembled monolayers (SAMs) to improve and tailor the photovoltaic performance of plasmonic hot-electron Schottky solar cells is presented. SAMs allow the simultaneous control of open-circuit voltage, hot-electron injection and short-circuit current. To that end, a plurality of molecule structural parameters can be adjusted: SAM molecule's length can be adjusted to control plasmonic hot electron injection. Modifying SAMs dipole moment allows for a precise tuning of the open-circuit voltage. The functionalization of the SAM can also be selected to modify short-circuit current. This allows the simultaneous achievement of high open-circuit voltages (0.56 V) and fill-factors (0.58), IPCE above 5% at the plasmon resonance and maximum power-conversion efficiencies of 0.11%, record for this class of devices. Electronic supplementary information (ESI) available: Contact-potential differentiometry measurements, FTIR characterization, performance statistics and gold devices. See DOI: 10.1039/c4nr06356b

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.

Multielectrode array recordings of bladder and perineal primary afferent activity from the sacral dorsal root ganglia

NASA Astrophysics Data System (ADS)

Bruns, Tim M.; Gaunt, Robert A.; Weber, Douglas J.

2011-10-01

The development of bladder and bowel neuroprostheses may benefit from the use of sensory feedback. We evaluated the use of high-density penetrating microelectrode arrays in sacral dorsal root ganglia (DRG) for recording bladder and perineal afferent activity. Arrays were inserted in S1 and S2 DRG in three anesthetized cats. Neural signals were recorded while the bladder volume was modulated and mechanical stimuli were applied to the perineal region. In two experiments, 48 units were observed that tracked bladder pressure with their firing rates (79% from S2). At least 50 additional units in each of the three experiments (274 total; 60% from S2) had a significant change in their firing rates during one or more perineal stimulation trials. This study shows the feasibility of obtaining bladder-state information and other feedback signals from the pelvic region with a sacral DRG electrode interface located in a single level. This natural source of feedback would be valuable for providing closed-loop control of bladder or other pelvic neuroprostheses.