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...

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

NASA Astrophysics Data System (ADS)

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

2015-05-01

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

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

Monochloramine-sensitive amperometric microelectrode: optimization of gold, platinum, and carbon fiber sensing materials for removal of dissolved oxygen interference

EPA Science Inventory

Amperometric monochloramine detection using newly fabricated gold, platinum, and carbon-fiber microsensors was investigated to optimize sensor operation and eliminate oxygen interference. Gold and platinum microsensors exhibited no oxygen interference during monochloramine measu...

Real-time monitoring of H2O2 release from single cells using nanoporous gold microelectrodes decorated with platinum nanoparticles.

PubMed

Xiao, Chong; Liu, Yan-Ling; Xu, Jia-Quan; Lv, Song-Wei; Guo, Shan; Huang, Wei-Hua

2015-06-07

Here, we report a self-supported nanoporous gold microelectrode decorated with well-dispersed and tiny platinum nanoparticles as an electrochemical nonenzymatic hydrogen peroxide biosensor. Nanoporous gold was fabricated by electrochemical alloying/dealloying and then small-sized platinum nanoparticles were electrodeposited uniformly on them. This novel hybrid nanostructure endows the sensor with high sensitivity and selectivity towards the reduction of hydrogen peroxide with a low detection limit of 0.3 nM. The sensor has been successfully applied for the measurement of H2O2 release from a single isolated human breast cancer cell, demonstrating its great potential for further physiological and pathological 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.

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.

Design and implementation of an array of micro-electrochemical detectors for two-dimensional liquid chromatography--proof of principle.

PubMed

Abia, Jude A; Putnam, Joel; Mriziq, Khaled; Guiochon, Georges A

2010-03-05

Simultaneous two-dimensional liquid chromatography (2D-LC) is an implementation of two-dimensional liquid chromatography which has the potential to provide very fast, yet highly efficient separations. It is based on the use of time x space and space x space separation systems. The basic principle of this instrument has been validated long ago by the success of two-dimensional thin layer chromatography. The construction of a pressurized wide and flat column (100 mm x 100 mm x 1 mm) operated under an inlet pressure of up to 50 bar was described previously. However, to become a modern analytical method, simultaneous 2D-LC requires the development of detectors suitable for the monitoring of the composition of the eluent of this pressurized planar, wide column. An array of five equidistant micro-electrochemical sensors was built for this purpose and tested. Each sensor is a three-electrode system, with the working electrode being a 25 microm polished platinum micro-electrode. The auxiliary electrode is a thin platinum wire and the reference electrode an Ag/AgCl (3M sat. KCl) electrode. In this first implementation, proof of principle is demonstrated, but the final instrument will require a much larger array. 2010 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-04-01

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

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

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.

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…

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.

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

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

PubMed Central

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

2010-01-01

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

A 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...

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.

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.

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.

Spatiotemporal norepinephrine mapping using a high-density CMOS microelectrode array.

PubMed

Wydallis, John B; Feeny, Rachel M; Wilson, William; Kern, Tucker; Chen, Tom; Tobet, Stuart; Reynolds, Melissa M; Henry, Charles S

2015-10-21

A high-density amperometric electrode array containing 8192 individually addressable platinum working electrodes with an integrated potentiostat fabricated using Complementary Metal Oxide Semiconductor (CMOS) processes is reported. The array was designed to enable electrochemical imaging of chemical gradients with high spatiotemporal resolution. Electrodes are arranged over a 2 mm × 2 mm surface area into 64 subarrays consisting of 128 individual Pt working electrodes as well as Pt pseudo-reference and auxiliary electrodes. Amperometric measurements of norepinephrine in tissue culture media were used to demonstrate the ability of the array to measure concentration gradients in complex media. Poly(dimethylsiloxane) microfluidics were incorporated to control the chemical concentrations in time and space, and the electrochemical response at each electrode was monitored to generate electrochemical heat maps, demonstrating the array's imaging capabilities. A temporal resolution of 10 ms can be achieved by simultaneously monitoring a single subarray of 128 electrodes. The entire 2 mm × 2 mm area can be electrochemically imaged in 64 seconds by cycling through all subarrays at a rate of 1 Hz per subarray. Monitoring diffusional transport of norepinephrine is used to demonstrate the spatiotemporal resolution capabilities of the system.

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.

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.

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

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.

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.

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.

Fabrication and surface-modification of implantable microprobes for neuroscience studies

NASA Astrophysics Data System (ADS)

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

2012-06-01

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

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.

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

PubMed

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

2014-01-01

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

A 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

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

Conducting polymer electrodes for visual prostheses.

PubMed

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

2010-01-01

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

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.

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.

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...

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.

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...

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.

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...

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.

Electrochemical direct immobilization of DNA sequences for label-free herpes virus detection

NASA Astrophysics Data System (ADS)

Tam, Phuong Dinh; Trung, Tran; Tuan, Mai Anh; Chien, Nguyen Duc

2009-09-01

DNA sequences/bio-macromolecules of herpes virus (5'-AT CAC CGA CCC GGA GAG GGA C-3') were directly immobilized into polypyrrole matrix by using the cyclic voltammetry method, and grafted onto arrays of interdigitated platinum microelectrodes. The morphology surface of the obtained PPy/DNA of herpes virus composite films was investigated by a FESEM Hitachi-S 4800. Fourier transform infrared spectroscopy (FTIR) was used to characterize the PPy/DNA film and to study the specific interactions that may exist between DNA biomacromolecules and PPy chains. Attempts are made to use these PPy/DNA composite films for label-free herpes virus detection revealed a response time of 60 s in solutions containing as low as 2 nM DNA concentration, and self life of six months when immerged in double distilled water and kept refrigerated.

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

EPA Science Inventory

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

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

EPA Science Inventory

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

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

EPA Science Inventory

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

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

EPA Science Inventory

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

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

PubMed

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

2009-07-21

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

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

PubMed Central

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

2010-01-01

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

Multi-electrode array technologies for neuroscience and cardiology

NASA Astrophysics Data System (ADS)

Spira, Micha E.; Hai, Aviad

2013-02-01

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

Multi-electrode array technologies for neuroscience and cardiology.

PubMed

Spira, Micha E; Hai, Aviad

2013-02-01

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

Bio-electrochemical microelectrode arrays for glutamate and electrophysiology detection in hippocampus of temporal lobe epileptic rats.

PubMed

Li, Ziyue; Song, Yilin; Xiao, Guihua; Gao, Fei; Xu, Shengwei; Wang, Mixia; Zhang, Yu; Guo, Fengru; Liu, Jie; Xia, Yang; Cai, Xinxia

2018-06-01

Temporal Lobe Epilepsy (TLE) is a chronic neurological disorder, characterized by sudden, repeated and transient central nervous system dysfunction. For better understanding of TLE, bio-nanomodified microelectrode arrays (MEA) are designed, for the achievement of high-quality simultaneous detection of glutamate signals (Glu) and multi-channel electrophysiological signals including action potentials (spikes) and local field potentials (LFPs). The MEA was fabricated by Micro-Electro-Mechanical System fabrication technology and all recording sites were modified with platinum black nano-particles, the average impedance decreased by nearly 90 times. Additionally, glutamate oxidase was also modified for the detection of Glu. The average sensitivity of the electrode in Glu solution was 1.999 ± 0.032 × 10 -2 pA/μM·μm 2 (n = 3) and linearity was R = 0.9986, with a good selectivity of 97.82% for glutamate and effective blocking of other interferents. In the in-vivo experiments, the MEA was subjected in hippocampus to electrophysiology and Glu concentration detection. During seizures, the fire rate of spikes increases, and the interspike interval is concentrated within 30 ms. The amplitude of LFPs increases by 3 times and the power increases. The Glu level (4.22 μM, n = 4) was obviously higher than normal rats (2.24 μM, n = 4). The MEA probe provides an advanced tool for the detection of dual-mode signals in the research of neurological diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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...

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...

Electrochemical characterisation and anodic stripping voltammetry at mesoporous platinum rotating disc electrodes.

PubMed

Lozano-Sanchez, Pablo; Elliott, Joanne M

2008-02-01

Using the technique of liquid crystal templating a rotating disc electrode (RDE) was modified with a high surface area mesoporous platinum film. The surface area of the electrode was characterised by acid voltammetry, and found to be very high (ca. 86 cm(2)). Acid characterisation of the electrode produced distorted voltammograms was interpreted as being due to the extremely large surface area which produced a combination of effects such as localised pH change within the pore environment and also ohmic drop effects. Acid voltammetry in the presence of two different types of surfactant, namely Tween 20 and Triton X-100, suggested antifouling properties associated with the mesoporous deposit. Further analysis of the modified electrode using a redox couple in solution showed typical RDE behaviour although extra capacitive currents were observed due to the large surface area of the electrode. The phenomenon of underpotential deposition was exploited for the purpose of anodic stripping voltammetry and results were compared with data collected for microelectrodes. Underpotential deposition of metal ions at the mesoporous RDE was found to be similar to that at conventional platinum electrodes and mesoporous microelectrodes although the rate of surface coverage was found to be slower at a mesoporous RDE. It was found that a mesoporous RDE forms a suitable system for quantification of silver ions in solution.

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

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...

Impedance biosensor for the rapid detection of Listeria spp. based on aptamer functionalized Pt-interdigitated microelectrodes array

NASA Astrophysics Data System (ADS)

Sidhu, R.; Rong, Y.; Vanegas, D. C.; Claussen, J.; McLamore, E. S.; Gomes, C.

2016-05-01

Listeria monocytogenes is one of the most common causes of food illness deaths worldwide, with multiple outbreaks in the United States alone. Current methods to detect foodborne pathogens are laborious and can take several hours to days to produce results. Thus, faster techniques are needed to detect bacteria within the same reliability level as traditional techniques. This study reports on a rapid, accurate, and sensitive aptamer biosensor device for Listeria spp. detection based on platinum interdigitated array microelectrodes (Pt-IDEs). Pt-IDEs with different geometric electrode gaps were fabricated by lithographic techniques and characterized by cyclic voltammetric (CV), electrochemical impedance spectroscopy (EIS), and potential amperometry (DCPA) measurements of reversible redox species. Based on these results, 50 μm Pt-IDE was chosen to further functionalize with a Listeria monocytogenes DNA aptamer selective to the cell surface protein internalin A, via metal-thiol self-assembly at the 5' end of the 47-mer's. EIS analysis was used to detect Listeria spp. without the need for label amplification and pre-concentration steps. The optimized aptamer concentration of 800 nM was selected to capture the bacteria through internalin A binding and the aptamer hairpin structure near the 3' end. The aptasensor was capable of detecting a wide range of bacteria concentration from 10 to 106 CFU/mL at lower detection limit of 5.39 +/- 0.21 CFU/mL with sensitivity of 268.1 +/- 25.40 (Ohms/log [CFU/mL]) in 17 min. The aptamer based biosensor offers a portable, rapid and sensitive alternative for food safety applications with one of the lowest detection limits reported to date.

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.

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...

Fabrication of a 3D micro/nano dual-scale carbon array and its demonstration as the microelectrodes for supercapacitors

NASA Astrophysics Data System (ADS)

Jiang, Shulan; Shi, Tielin; Gao, Yang; Long, Hu; Xi, Shuang; Tang, Zirong

2014-04-01

An easily accessible method is proposed for the fabrication of a 3D micro/nano dual-scale carbon array with a large surface area. The process mainly consists of three critical steps. Firstly, a hemispherical photoresist micro-array was obtained by the cost-effective nanoimprint lithography process. Then the micro-array was transformed into hierarchical structures with longitudinal nanowires on the microstructure surface by oxygen plasma etching. Finally, the micro/nano dual-scale carbon array was fabricated by carbonizing these hierarchical photoresist structures. It has also been demonstrated that the micro/nano dual-scale carbon array can be used as the microelectrodes for supercapacitors by the electrodeposition of a manganese dioxide (MnO2) film onto the hierarchical carbon structures with greatly enhanced electrochemical performance. The specific gravimetric capacitance of the deposited micro/nano dual-scale microelectrodes is estimated to be 337 F g-1 at the scan rate of 5 mV s-1. This proposed approach of fabricating a micro/nano dual-scale carbon array provides a facile way in large-scale microstructures’ manufacturing for a wide variety of applications, including sensors and on-chip energy storage devices.

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-01-01

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

Pulse Voltammetry in Single Cells Using Platinum Microelectrodes

DTIC Science & Technology

1991-11-22

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

Conical Tungsten Tips as Substrates for the Preparation of Ultramicroelectrodes

PubMed Central

Hermans, Andre; Wightman, R. Mark

2008-01-01

Here we describe a simple method to prepare voltammetric microelectrodes using tungsten wires as a substrate. Tungsten wires have high tensile modulus and enable the fabrication of electrodes that have small dimensions overall while retaining rigidity. In this work, 125 μm tungsten wires with a conical tip were employed. For the preparation of gold or platinum ultramicroelectrodes, commercial tungsten microelectrodes, completely insulated except at the tip, were used as substrates. Following removal of oxides from the exposed tungsten, platinum or gold was electroplated yielding surfaces with an electroactive area of between 1×10−6 cm2 to 2×10−6 cm2. Carbon surfaces on the etched tip of tungsten microwires were prepared by coating with photoresist followed by pyrolysis. The entire electrode was then insulated with Epoxylite except the tip yielding an exposed carbon surface with an area of around 4×10−6 cm2 to 6×10−6 cm2. All three types of ultramicroelectrodes fabricated on the tungsten wire had similar electrochemical behavior to electrodes fabricated from wires or fibers insulated with glass tubes. PMID:17129002

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.

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).

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.

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.

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.

CMOS-micromachined, two-dimenisional transistor arrays for neural recording and stimulation.

PubMed

Lin, J S; Chang, S R; Chang, C H; Lu, S C; Chen, H

2007-01-01

In-plane microelectrode arrays have proven to be useful tools for studying the connectivities and the functions of neural tissues. However, seldom microelectrode arrays are monolithically-integrated with signal-processing circuits, without which the maximum number of electrodes is limited by the compromise with routing complexity and interferences. This paper proposes a CMOS-compatible, two-dimensional array of oxide-semiconductor field-effect transistors(OSFETs), capable of both recording and stimulating neuronal activities. The fabrication of the OSFETs not only requires simply die-level, post-CMOS micromachining process, but also retains metal layers for monolithic integration with signal-processing circuits. A CMOS microsystem containing the OSFET arrays and gain-programmable recording circuits has been fabricated and tested. The preliminary testing results are presented and discussed.

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.

Chemically Modified Microelectrode Arrays. New Kinds of Electronic Devices.

DTIC Science & Technology

1987-08-05

switching. Figure 1 shows a typical process for the fabrication of a microelectrode array consisting of eight, individually addressable Au (or Pt...S4r... -n - 2 ORGANIC CLEAN MRC SPUTTERING PHOTOLITHOGRAPHY _Suttred SI.N, & DRY ETCH _LorVO S1. 1.2 pm Figure 1. Flow chart for fabrication of...microelectrochemical devices, including polypyrrole, 14 poly(N-methylpyrrole), 14b poly(3-methylthiophene), 1 5 and polyaniline .15b,16 These materials can all be made by

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.

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

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

Growth of arrays of oriented epitaxial platinum nanoparticles with controlled size and shape by natural colloidal lithography

DOE PAGES

Komanicky, Vladimir; Barbour, Andi; Lackova, Miroslava; ...

2014-07-05

Here, we developed a method for production of arrays of platinum nanocrystals of controlled size and shape using templates from ordered silica bead monolayers. Silica beads with nominal sizes of 150 and 450 nm were self-assembl into monolayers over strontium titanate single crystal substrates. The monolayers were used as shadow masks for platinum metal deposition on the substrate using the three-step evaporation technique. Produced arrays of epitaxial platinum islands were transformed into nanocrystals by annealing in a quartz tube in nitrogen flow. The shape of particles is determined by the substrate crystallography, while the size of the particles and theirmore » spacing are controlled by the size of the silica beads in the mono- layer mask. As a proof of concept, arrays of platinum nanocrystals of cubooctahedral shape were prepared on (100) strontium titanate substrates. We also characterized the nanocrystal arrays by atomic force microscopy, scanning electron microscopy, and synchrotron X-ray diffraction techniques.« less

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.

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.

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

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.

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.

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

NASA Astrophysics Data System (ADS)

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

2012-12-01

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

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

Temperature dependence of the electrode kinetics of oxygen reduction at the platinum/Nafion interface - A microelectrode investigation

NASA Technical Reports Server (NTRS)

Parthasarathy, Arvind; Srinivasan, Supramanian; Appleby, A. J.; Martin, Charles R.

1992-01-01

Results of a study of the temperature dependence of the oxygen reduction kinetics at the Pt/Nafion interface are presented. This study was carried out in the temperature range of 30-80 C and at 5 atm of oxygen pressure. The results showed a linear increase of the Tafel slope with temperature in the low current density region, but the Tafel slope was found to be independent of temperature in the high current density region. The values of the activation energy for oxygen reduction at the platinum/Nafion interface are nearly the same as those obtained at the platinum/trifluoromethane sulfonic acid interface but less than values obtained at the Pt/H3PO4 and Pt/HClO4 interfaces. The diffusion coefficient of oxygen in Nafion increases with temperature while its solubility decreases with temperature. These temperatures also depend on the water content of the membrane.

Arrays of very small voltammetric electrodes based on reticulated vitreous carbon

NASA Astrophysics Data System (ADS)

Sleszynski, N.; Osteryoung, J.; Carter, M.

1983-10-01

Micro-electrode arrays constructed from reticulated vitreous carbon are described and characterized. Sterological analysis and cyclic voltammetric data indicate the arrays have equivalent radii as small as 32 microns, with densities as high as 1650 electrodes/sq cm.

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

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

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

Multichannel microchip electrophoresis device fabricated in polycarbonate with an integrated contact conductivity sensor array.

PubMed

Shadpour, Hamed; Hupert, Mateusz L; Patterson, Donald; Liu, Changgeng; Galloway, Michelle; Stryjewski, Wieslaw; Goettert, Jost; Soper, Steven A

2007-02-01

A 16-channel microfluidic chip with an integrated contact conductivity sensor array is presented. The microfluidic network consisted of 16 separation channels that were hot-embossed into polycarbonate (PC) using a high-precision micromilled metal master. All channels were 40 microm deep and 60 microm wide with an effective separation length of 40 mm. A gold (Au) sensor array was lithographically patterned onto a PC cover plate and assembled to the fluidic chip via thermal bonding in such a way that a pair of Au microelectrodes (60 microm wide with a 5 microm spacing) was incorporated into each of the 16 channels and served as independent contact conductivity detectors. The spacing between the corresponding fluidic reservoirs for each separation channel was set to 9 mm, which allowed for loading samples and buffers to all 40 reservoirs situated on the microchip in only five pipetting steps using an 8-channel pipettor. A printed circuit board (PCB) with platinum (Pt) wires was used to distribute the electrophoresis high-voltage to all reservoirs situated on the fluidic chip. Another PCB was used for collecting the conductivity signals from the patterned Au microelectrodes. The device performance was evaluated using microchip capillary zone electrophoresis (mu-CZE) of amino acid, peptide, and protein mixtures as well as oligonucleotides that were separated via microchip capillary electrochromatography (mu-CEC). The separations were performed with an electric field (E) of 90 V/cm and were completed in less than 4 min in all cases. The conductivity detection was carried out using a bipolar pulse voltage waveform with a pulse amplitude of +/-0.6 V and a frequency of 6.0 kHz. The conductivity sensor array concentration limit of detection (SNR = 3) was determined to be 7.1 microM for alanine. The separation efficiency was found to be 6.4 x 10(4), 2.0 x 10(3), 4.8 x 10(3), and 3.4 x 10(2) plates for the mu-CEC of the oligonucleotides and mu-CZE of the amino acids, peptides, and proteins, respectively, with an average channel-to-channel migration time reproducibility of 2.8%. The average resolution obtained for mu-CEC of the oligonucleotides and mu-CZE of the amino acids, peptides, and proteins was 4.6, 1.0, 0.9, and 1.0, respectively. To the best of our knowledge, this report is the first to describe a multichannel microchip electrophoresis device with integrated contact conductivity sensor array.

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

PubMed Central

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

2010-01-01

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

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.

Synthesis and characterization of Ru-Ti[sub 4]O[sub 7] microelectrode arrays

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

He, L.; Franzen, H.F.; Vitt, J.E.

1994-04-01

A synthesis is described for Ru microelectrode arrays within a conductive Ti[sub 4]O[sub 7] ceramic matrix. Data obtained by X-ray diffractometry and scanning electron microscopy are consistent with the existence of heterogeneous mixtures of Ru particles (ca. 0.8 [mu]m diam) within the Ti[sub 4]O[sub 7] matrices. No mixed metal oxides or other new compounds are detected. Rotated disk electrodes (RDEs) constructed from the Ru-Ti[sub 4]O[sub 7] materials are compared on the basis of their voltammetric response for the oxidations of I[sup [minus

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.

Antibacterial activity of microstructured sacrificial anode thin films by combination of silver with platinum group elements (platinum, palladium, iridium).

PubMed

Köller, Manfred; Bellova, Petri; Javid, Siyamak Memar; Motemani, Yahya; Khare, Chinmay; Sengstock, Christina; Tschulik, Kristina; Schildhauer, Thomas A; Ludwig, Alfred

2017-05-01

Five different Ag dots arrays (16 to 400dots/mm 2 ) were fabricated on a continuous platinum, palladium, or iridium thin film and for comparison also on titanium film by sputter deposition and photolithographic patterning. To analyze the antibacterial activity of these microstructured films Staphylococcus aureus (S. aureus) were placed onto the array surfaces and cultivated overnight. To analyze the viability of planktonic as well as surface adherent bacteria, the applied bacterial fluid was subsequently aspirated, plated on blood agar plates and adherent bacteria were detected by fluorescence microscopy. A particular antibacterial effect towards S. aureus was induced by Ag dot arrays on each of the platinum group thin film (sacrificial anode system for Ag) in contrast to Ag dot arrays fabricated on the Ti thin films (non-sacrificial anode system for Ag). Among platinum group elements the Ir-Ag system exerted the highest antibacterial activity which was accompanied by most advanced dissolution of the Ag dots and Ag ion release compared to Ag dots on Pt or Pd. Copyright © 2016 Elsevier B.V. All rights reserved.

Localized Synthesis of Conductive Copper-Tetracyanoquinodimethane Nanostructures in Ultrasmall Microchambers for Nanoelectronics.

PubMed

Xing, Yanlong; Sun, Guoguang; Speiser, Eugen; Esser, Norbert; Dittrich, Petra S

2017-05-24

In this work, the microfluidic-assisted synthesis of copper-tetracyanoquinodimethane (Cu-TCNQ) nanostructures in an ambient environment is reported for the first time. A two-layer microfluidic device comprising parallel actuated microchambers was used for the synthesis and enabled excellent fluid handling for the continuous and multiple chemical reactions in confined ultrasmall chambers. Different precautions were applied to ensure the reduction state of copper (Cu) for the synthesis of Cu-TCNQ charge-transfer compounds. The localized synthesis of Cu and in situ transformation to Cu-TCNQ complexes in solution were achieved by applying different gas pressures in the control layer. Additionally, various diameters of the Cu-TCNQ nano/microstructures were obtained by adjusting the concentration of the precursors and reaction time. After the synthesis, platinum (Pt) microelectrode arrays, which were aligned at the microchambers, could enable the in situ measurements of the electronic properties of the synthesized nanostructures without further manipulation. The as-prepared Cu-TCNQ wire bundles showed good conductivity and a reversible hysteretic switching effect, which proved the possibility in using them to build advanced nanoelectronics.

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.

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

NASA Astrophysics Data System (ADS)

Guo, Rui; Liu, Jing

2017-10-01

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

Heterogeneous distribution of exocytotic microdomains in adrenal chromaffin cells resolved by high-density diamond ultra-microelectrode arrays.

PubMed

Gosso, Sara; Turturici, Marco; Franchino, Claudio; Colombo, Elisabetta; Pasquarelli, Alberto; Carbone, Emilio; Carabelli, Valentina

2014-08-01

Here we describe the ability of a high-density diamond microelectrode array targeted to resolve multi-site detection of fast exocytotic events from single cells. The array consists of nine boron-doped nanocrystalline diamond ultra-microelectrodes (9-Ch NCD-UMEA) radially distributed within a circular area of the dimensions of a single cell. The device can be operated in voltammetric or chronoamperometric configuration. Sensitivity to catecholamines, tested by dose-response calibrations, set the lowest detectable concentration of adrenaline to ∼5 μm. Catecholamine release from bovine or mouse chromaffin cells could be triggered by electrical stimulation or external KCl-enriched solutions. Spikes detected from the cell apex using carbon fibre microelectrodes showed an excellent correspondence with events measured at the bottom of the cell by the 9-Ch NCD-UMEA, confirming the ability of the array to resolve single quantal secretory events. Subcellular localization of exocytosis was provided by assigning each quantal event to one of the nine channels based on its location. The resulting mapping highlights the heterogeneous distribution of secretory activity in cell microdomains of 12-27 μm2. In bovine chromaffin cells, secretion was highly heterogeneous with zones of high and medium activity in 54% of the cell surface and zones of low or no activity in the remainder. The 'non-active' ('silent') zones covered 24% of the total and persisted for 6-8 min, indicating stable location. The 9-Ch NCD-UMEA therefore appears suitable for investigating the microdomain organization of neurosecretion with high spatial resolution. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

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.

Pressure dependence of the oxygen reduction reaction at the platinum microelectrode/nafion interface - Electrode kinetics and mass transport

NASA Technical Reports Server (NTRS)

Parthasarathy, Arvind; Srinivasan, Supramaniam; Appleby, A. J.; Martin, Charles R.

1992-01-01

The investigation of oxygen reduction kinetics at the platinum/Nafion interface is of great importance in the advancement of proton-exchange-membrane (PEM) fuel-cell technology. This study focuses on the dependence of the oxygen reduction kinetics on oxygen pressure. Conventional Tafel analysis of the data shows that the reaction order with respect to oxygen is unity at both high and low current densities. Chronoamperometric measurements of the transport parameters for oxygen in Nafion show that oxygen dissolution follows Henry's isotherm. The diffusion coefficient of oxygen is invariant with pressure; however, the diffusion coefficient for oxygen is lower when air is used as the equilibrating gas as compared to when oxygen is used for equilibration. These results are of value in understanding the influence of O2 partial pressure on the performance of PEM fuel cells and also in elucidating the mechanism of oxygen reduction at the platinum/Nafion interface.

Compact microelectrode array system: tool for in situ monitoring of drug effects on neurotransmitter release from neural cells.

PubMed

Chen, Yu; Guo, Chunxian; Lim, Layhar; Cheong, Serchoong; Zhang, Qingxin; Tang, Kumcheong; Reboud, Julien

2008-02-15

This paper presents a compact microelectrode array (MEA) system, to study potassium ion-induced dopamine release from PC12 neural cells, without relying on a micromanipulator and a microscope. The MEA chip was integrated with a custom-made "test jig", which provides a robust electrical interfacing tool between the microchip and the macroenvironment, together with a potentiostat and a microfluidic syringe pump. This integrated system significantly simplifies the operation procedures, enhances sensing performance, and reduces fabrication costs. The achieved detection limit for dopamine is 3.8 x 10-2 muM (signal/noise, S/N = 3) and the dopamine linear calibration range is up to 7.39 +/- 0.06 muM (mean +/- SE). The effects of the extracelluar matrix collagen coating of the microelectrodes on dopamine sensing behaviors, as well as the influences of K+ and l-3,4-digydroxyphenylalanine concentrations and incubation times on dopamine release, were extensively studied. The results show that our system is well suited for biologists to study chemical release from living cells as well as drug effects on secreting cells. The current system also shows a potential for further improvements toward a multichip array system for drug screening applications.

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

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.

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.

Highly sensitive detection of quantal dopamine secretion from pheochromocytoma cells using neural microelectrode array electrodeposited with polypyrrole graphene.

PubMed

Wang, Li; Xu, Huiren; Song, Yilin; Luo, Jinping; Wei, Wenjing; Xu, Shengwei; Cai, Xinxia

2015-04-15

For the measurement of events of dopamine (DA) release as well as the coordinating neurotransmission in the nerve system, a neural microelectrode array (nMEA) electrodeposited directionally with polypyrrole graphene (PG) nanocomposites was fabricated. The deposited graphene significantly increased the surface area of working electrode, which led to the nMEA (with diameter of 20 μm) with excellent selectivity and sensitivity to DA. Furthermore, PG film modification exhibited low detection limit (4 nM, S/N = 3.21), high sensitivity, and good linearity in the presence of ascorbic acid (e.g., 13933.12 μA mM(-1) cm(-2) in the range of 0.8-10 μM). In particular, the nMEA combined with the patch-clamp system was used to detect quantized DA release from pheochromocytoma cells under 100 mM K(+) stimulation. The nMEA that integrates 60 microelectrodes is novel for detecting a large number of samples simultaneously, which has potential for neural communication research.

Kinetics determination of electrogenerated hydrogen peroxide (H2O2) using carbon fiber microelectrode in electroenzymatic degradation of phenolic compounds.

PubMed

Cho, Seung-Hee; Jang, Am; Bishop, Paul L; Moon, Seung-Hyeon

2010-03-15

The kinetics of electrogenerated hydrogen peroxide (H(2)O(2)), which can activate peroxidases in an electroenzymatic process, was examined by an amperometric technique using a carbon fiber microelectrode that was modified by polyaniline (PAn) film and platinum particles. The electrogeneration of H(2)O(2) was found to be dependent on the pH and applied potential, and resulting in a variable current response of the carbon fiber microelectrode. The highest amount of H(2)O(2) was electrogenerated when 2.3 V was applied between the Pt/Ti anode and a reticulated vitreous carbon (RVC) cathode at pH 6.0, with a current response of 0.0190 microA min(-1). Phenol was completely degraded by the electroenzymatic reaction of the immobilized horseradish peroxidase (HRP), and the time required for the electrogeneration of H(2)O(2) increased according to the initial concentration of phenol. The degradation stoichiometric ratio between the electrogenerated H(2)O(2) and the aqueous phenol under HRP immobilized on RVC was found to be 1:1. (c) 2009 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

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.

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.

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.

Fabrication of Carbon-Platinum Interdigitated Array Electrodes and Their Application for Investigating Homogeneous Hydrogen Evolution Catalysis

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

Liu, F.; Divan, R.; Parkinson, B. A.

2015-01-01

Interdigitated array electrodes (IDAEs) with one carbon electrode and the other platinum electrode were constructed by electrodepositing platinum on one set of the carbon electrodes. Platinum deposition was confirmed by scanning electron microscope (SEM) and cyclic voltammetry. The width of the carbon and platinum digits is less than 2 μm and the gap between two adjacent digits is around 3 μm. The carbon-platinum IDAEs benefit from the characteristics of both carbon and platinum in that carbon can provide a wide nonreactive potential window while platinum is a good catalyst for hydrogen reactions making it useful to characterize the catalytic hydrogenmore » production cycle of the molecular electrocatalyst [Ni(PPh2NPh2)2(CH3CN)](BF4)2 (where PPh2NPh2 is 1,3,5,7-tetraphenyl-1,5-diaza-3,7-diphosphacyclooctane). With properly set potentials, the molecular electrocatalyst was reduced at the carbon digits to initiate a homogeneous H2 production reaction while the platinum digits detect the H2 by oxidation, providing direct evidence of its production rate from the catalytic cycles.« less

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 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

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

Micromachined devices for interfacing neurons

NASA Astrophysics Data System (ADS)

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

1998-07-01

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

Bacterial handling under the influence of non-uniform electric fields: dielectrophoretic and electrohydrodynamic effects.

PubMed

Fernádez-Morales, Flavio H; Duarte, Julio E; Samitier-Martí, Josep

2008-12-01

This paper describes the modeling and experimental verification of a castellated microelectrode array intended to handle biocells, based on common dielectrophoresis. The proposed microsystem was developed employing platinum electrodes deposited by lift-off, silicon micromachining, and photoresin patterning techniques. Having fabricated the microdevice it was tested employing Escherichia coli as bioparticle model. Positive dielectrophoresis could be verified with the selected cells for frequencies above 100 kHz, and electrohydrodynamic effects were observed as the dominant phenomena when working at lower frequencies. As a result, negative dielectrophoresis could not be observed because its occurrence overlaps with electrohydrodynamic effects; i.e. the viscous drag force acting on the particles is greater than the dielectrophoretic force at frequencies where negative dielectrophoresis should occur. The experiments illustrate the convenience of this kind of microdevices to micro handling biological objects, opening the possibility for using these microarrays with other bioparticles. Additionally, liquid motion as a result of electrohydrodynamic effects must be taken into account when designing bioparticle micromanipulators, and could be used as mechanism to clean the electrode surfaces, that is one of the most important problems related to this kind of devices.

Microfluidic Arrayed Lab-On-A-Chip for Electrochemical Capacitive Detection of DNA Hybridization Events.

PubMed

Ben-Yoav, Hadar; Dykstra, Peter H; Bentley, William E; Ghodssi, Reza

2017-01-01

A microfluidic electrochemical lab-on-a-chip (LOC) device for DNA hybridization detection has been developed. The device comprises a 3 × 3 array of microelectrodes integrated with a dual layer microfluidic valved manipulation system that provides controlled and automated capabilities for high throughput analysis of microliter volume samples. The surface of the microelectrodes is functionalized with single-stranded DNA (ssDNA) probes which enable specific detection of complementary ssDNA targets. These targets are detected by a capacitive technique which measures dielectric variation at the microelectrode-electrolyte interface due to DNA hybridization events. A quantitative analysis of the hybridization events is carried out based on a sensing modeling that includes detailed analysis of energy storage and dissipation components. By calculating these components during hybridization events the device is able to demonstrate specific and dose response sensing characteristics. The developed microfluidic LOC for DNA hybridization detection offers a technology for real-time and label-free assessment of genetic markers outside of laboratory settings, such as at the point-of-care or in-field environmental monitoring.

A fast stimulability screening protocol for neuronal cultures on microelectrode arrays.

PubMed

Kapucu, Fikret E; Tanskanen, Jarno M A; Yuan, Yuting; Hyttinen, Jari A K

2015-01-01

Microelectrode arrays (MEAs) are used to study the electrical activity in brain slices and neuronal cultures. MEA experiments for the analysis of electrical stimulation responses require the tissue or culture to be prone to stimulation. For brain slices, potential stimulation sites may be directly visible in microscope, in which case the determination of stimulability at those locations is sufficient. In unstructured neuronal cultures, potential stimulation sites may not be known a priori, and spatial stimulability screening should be performed. Considering, e.g., 59 microelectrode sites, each to be stimulated several times, may result in long screening times, unacceptable with a MEA system without an integrated CO2 incubator, or in high stimulation effects on the networks. Here, we describe an implementation of a fast stimulation protocol employing pseudorandom stimulation site switching aiming at alleviating the network effects of the stimulability screening. In this paper, we show the usability of the proposed protocol by first detecting stimulable locations and subsequently apply repeated stimulation on the identified potentially stimulable locations to observe an exemplary neuronal pathway.

Fabrication of two-layer poly(dimethyl siloxane) devices for hydrodynamic cell trapping and exocytosis measurement with integrated indium tin oxide microelectrodes arrays

PubMed Central

Gao, Changlu; Sun, Xiuhua; Gillis, Kevin D.

2016-01-01

The design, fabrication and test of a microfluidic cell trapping device to measure single cell exocytosis were reported. Research on the patterning of double layer template based on repetitive standard photolithography of AZ photoresist was investigated. The replicated poly(dimethyl siloxane) devices with 2.5 μm deep channels were proved to be efficient for stopping cells. Quantal exocytosis measurement can be achieved by targeting single or small clumps of chromaffin cells on top of the 10 μm ×10 μm indium tin oxide microelectrodes arrays with the developed microdevice. And about 72% of the trapping sites can be occupied by cells with hydrodynamic trapping method and the recorded amperometric signals are comparable to the results with traditional carbon fiber microelectrodes. The method of manufacturing the microdevices is simple, low-cost and easy to perform. The manufactured device offers a platform for the high throughput detection of quantal catecholamine exocytosis from chromaffin cells with sufficient sensitivity and broad application. PMID:23329291

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.

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.

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

[Flexible print circuit technology application in biomedical engineering].

PubMed

Jiang, Lihua; Cao, Yi; Zheng, Xiaolin

2013-06-01

Flexible print circuit (FPC) technology has been widely applied in variety of electric circuits with high precision due to its advantages, such as low-cost, high specific fabrication ability, and good flexibility, etc. Recently, this technology has also been used in biomedical engineering, especially in the development of microfluidic chip and microelectrode array. The high specific fabrication can help making microelectrode and other micro-structure equipment. And good flexibility allows the micro devices based on FPC technique to be easily packaged with other parts. In addition, it also reduces the damage of microelectrodes to the tissue. In this paper, the application of FPC technology in biomedical engineering is introduced. Moreover, the important parameters of FPC technique and the development trend of prosperous applications is also discussed.

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

Theoretical analysis of intracortical microelectrode recordings

NASA Astrophysics Data System (ADS)

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

2011-08-01

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

Theoretical analysis of intracortical microelectrode recordings

PubMed Central

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

2011-01-01

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

Separation of submicron bioparticles by dielectrophoresis.

PubMed Central

Morgan, H; Hughes, M P; Green, N G

1999-01-01

Submicron particles such as latex spheres and viruses can be manipulated and characterized using dielectrophoresis. By the use of appropriate microelectrode arrays, particles can be trapped or moved between regions of high or low electric fields. The magnitude and direction of the dielectrophoretic force on the particle depends on its dielectric properties, so that a heterogeneous mixture of particles can be separated to produce a more homogeneous population. In this paper the controlled separation of submicron bioparticles is demonstrated. With electrode arrays fabricated using direct write electron beam lithography, it is shown that different types of submicron latex spheres can be spatially separated. The separation occurs as a result of differences in magnitude and/or direction of the dielectrophoretic force on different populations of particles. These differences arise mainly because the surface properties of submicron particles dominate their dielectrophoretic behavior. It is also demonstrated that tobacco mosaic virus and herpes simplex virus can be manipulated and spatially separated in a microelectrode array. PMID:10388776

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.

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

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.

[Finite element analysis of temperature field of retina by electrical stimulation with microelectrode array].

PubMed

Wang, Wei; Qiao, Qingli; Gao, Weiping; Wu, Jun

2014-12-01

We studied the influence of electrode array parameters on temperature distribution to the retina during the use of retinal prosthesis in order to avoid thermal damage to retina caused by long-term electrical stimulation. Based on real epiretinal prosthesis, a three-dimensional model of electrical stimulation for retina with 4 X 4 microelectrode array had been established using the finite element software (COMSOL Multiphysics). The steady-state temperature field of electrical stimulation of the retina was calculated, and the effects of the electrode parameters such as the distance between the electrode contacts, the materials and area of the electrode contact on temperature field were considered. The maximum increase in the retina steady temperature was about 0. 004 degrees C with practical stimulation current. When the distance between the electrode contacts was changed from 130 microm to 520 microm, the temperature was reduced by about 0.006 microC. When the contact radius was doubled from 130 microm to 260 microm, the temperature decrease was about 0.005 degrees C. It was shown that there were little temperature changes in the retina with a 4 x 4 epiretinal microelectrode array, reflecting the safety of electrical stimulation. It was also shown that the maximum temperature in the retina decreased with increasing the distance between the electrode contacts, as well as increasing the area of electrode contact. However, the change of the maximum temperature was very small when the distance became larger than the diameter of electrode contact. There was no significant difference in the effects of temperature increase among the different electrode materials. Rational selection of the distance between the electrode contacts and their area in electrode design can reduce the temperature rise induced by electrical stimulation.

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

Artificial retina model for the retinally blind based on wavelet transform

NASA Astrophysics Data System (ADS)

Zeng, Yan-an; Song, Xin-qiang; Jiang, Fa-gang; Chang, Da-ding

2007-01-01

Artificial retina is aimed for the stimulation of remained retinal neurons in the patients with degenerated photoreceptors. Microelectrode arrays have been developed for this as a part of stimulator. Design such microelectrode arrays first requires a suitable mathematical method for human retinal information processing. In this paper, a flexible and adjustable human visual information extracting model is presented, which is based on the wavelet transform. With the flexible of wavelet transform to image information processing and the consistent to human visual information extracting, wavelet transform theory is applied to the artificial retina model for the retinally blind. The response of the model to synthetic image is shown. The simulated experiment demonstrates that the model behaves in a manner qualitatively similar to biological retinas and thus may serve as a basis for the development of an artificial retina.

Flexible nanohybrid microelectrode based on carbon fiber wrapped by gold nanoparticles decorated nitrogen doped carbon nanotube arrays: In situ electrochemical detection in live cancer cells.

PubMed

Zhang, Yan; Xiao, Jian; Sun, Yimin; Wang, Lu; Dong, Xulin; Ren, Jinghua; He, Wenshan; Xiao, Fei

2018-02-15

The rapidly growing demand for in situ real-time monitoring of chemical information in vitro and in vivo has attracted tremendous research efforts into the design and construction of high-performance biosensor devices. Herein, we develop a new type of flexible nanohybrid microelectrode based on carbon fiber wrapped by gold nanoparticles decorated nitrogen-doped carbon nanotube arrays, and explore its practical application in in situ electrochemical detection of cancer biomarker H 2 O 2 secreted from live cancer cells. Our results demonstrate that carbon fiber material with microscale size and fascinating mechanical properties can be used as a robust and flexible microelectrode substrate in the electrochemical biosensor system. And the highly ordered nitrogen-doped carbon nanotube arrays that grown on carbon fiber possess high surface area-to-volume ratio and abundant active sites, which facilitate the loading of high-density and uniformly dispersed gold nanoparticles on it. Benefited from the unique microstructure and excellent electrocatalytic properties of different components in the nanohybrid fiber microelectrode, an effective electrochemical sensing platform based on it has been built up for the sensitive and selective detection of H 2 O 2 , the detection limit is calculated to be 50nM when the signal-to-noise ratio is 3:1, and the linear dynamic range is up to 4.3mM, with a high sensitivity of 142µAcm -2 mM -1 . These good sensing performances, coupled with its intrinsic mechanical flexibility and biocompatibility, allow for its use in in situ real-time tracking H 2 O 2 secreted from breast cancer cell lines MCF-7 and MBA-MD-231, and evaluating the sensitivity of different cancer cells to chemotherapy or radiotherapy treatments, which hold great promise for clinic application in cancer diagnose and management. Copyright © 2017 Elsevier B.V. All rights reserved.

Miniaturized multiplex label-free electronic chip for rapid nucleic acid analysis based on carbon nanotube nanoelectrode arrays

NASA Technical Reports Server (NTRS)

Koehne, Jessica E.; Chen, Hua; Cassell, Alan M.; Ye, Qi; Han, Jie; Meyyappan, Meyya; Li, Jun

2004-01-01

BACKGROUND: Reducing cost and time is the major concern in clinical diagnostics, particularly in molecular diagnostics. Miniaturization technologies have been recognized as promising solutions to provide low-cost microchips for diagnostics. With the recent advancement in nanotechnologies, it is possible to further improve detection sensitivity and simplify sample preparation by incorporating nanoscale elements in diagnostics devices. A fusion of micro- and nanotechnologies with biology has great potential for the development of low-cost disposable chips for rapid molecular analysis that can be carried out with simple handheld devices. APPROACH: Vertically aligned multiwalled carbon nanotubes (MWNTs) are fabricated on predeposited microelectrode pads and encapsulated in SiO2 dielectrics with only the very end exposed at the surface to form an inlaid nanoelectrode array (NEA). The NEA is used to collect the electrochemical signal associated with the target molecules binding to the probe molecules, which are covalently attached to the end of the MWNTs. CONTENT: A 3 x 3 microelectrode array is presented to demonstrate the miniaturization and multiplexing capability. A randomly distributed MWNT NEA is fabricated on each microelectrode pad. Selective functionalization of the MWNT end with a specific oligonucleotide probe and passivation of the SiO2 surface with ethylene glycol moieties are discussed. Ru(bpy)2+ -mediator-amplified guanine oxidation is used to directly measure the electrochemical signal associated with target molecules. SUMMARY: The discussed MWNT NEAs have ultrahigh sensitivity in direct electrochemical detection of guanine bases in the nucleic acid target. Fewer than approximately 1000 target nucleic acid molecules can be measured with a single microelectrode pad of approximately 20 x 20 microm2, which approaches the detection limit of laser scanners in fluorescence-based DNA microarray techniques. MWNT NEAs can be easily integrated with microelectronic circuitry and microfluidics for development of a fully automated system for rapid molecular analysis with minimum cost.

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.

Using Microelectrode Arrays for Neurotoxicity Screening

EPA Science Inventory

Chemicals can disrupt nervous system electrical activity, rapidly causing toxicity prior to, or in the absence of, biochemical or morphological changes. However, high-throughput, functional approaches to detect chemical induced changes in electrical excitability are lacking. Micr...

A Radiosonde Using a Humidity Sensor Array with a Platinum Resistance Heater and Multi-Sensor Data Fusion

PubMed Central

Shi, Yunbo; Luo, Yi; Zhao, Wenjie; Shang, Chunxue; Wang, Yadong; Chen, Yinsheng

2013-01-01

This paper describes the design and implementation of a radiosonde which can measure the meteorological temperature, humidity, pressure, and other atmospheric data. The system is composed of a CPU, microwave module, temperature sensor, pressure sensor and humidity sensor array. In order to effectively solve the humidity sensor condensation problem due to the low temperatures in the high altitude environment, a capacitive humidity sensor including four humidity sensors to collect meteorological humidity and a platinum resistance heater was developed using micro-electro-mechanical-system (MEMS) technology. A platinum resistance wire with 99.999% purity and 0.023 mm in diameter was used to obtain the meteorological temperature. A multi-sensor data fusion technique was applied to process the atmospheric data. Static and dynamic experimental results show that the designed humidity sensor with platinum resistance heater can effectively tackle the sensor condensation problem, shorten response times and enhance sensitivity. The humidity sensor array can improve measurement accuracy and obtain a reliable initial meteorological humidity data, while the multi-sensor data fusion technique eliminates the uncertainty in the measurement. The radiosonde can accurately reflect the meteorological changes. PMID:23857263

A radiosonde using a humidity sensor array with a platinum resistance heater and multi-sensor data fusion.

PubMed

Shi, Yunbo; Luo, Yi; Zhao, Wenjie; Shang, Chunxue; Wang, Yadong; Chen, Yinsheng

2013-07-12

This paper describes the design and implementation of a radiosonde which can measure the meteorological temperature, humidity, pressure, and other atmospheric data. The system is composed of a CPU, microwave module, temperature sensor, pressure sensor and humidity sensor array. In order to effectively solve the humidity sensor condensation problem due to the low temperatures in the high altitude environment, a capacitive humidity sensor including four humidity sensors to collect meteorological humidity and a platinum resistance heater was developed using micro-electro-mechanical-system (MEMS) technology. A platinum resistance wire with 99.999% purity and 0.023 mm in diameter was used to obtain the meteorological temperature. A multi-sensor data fusion technique was applied to process the atmospheric data. Static and dynamic experimental results show that the designed humidity sensor with platinum resistance heater can effectively tackle the sensor condensation problem, shorten response times and enhance sensitivity. The humidity sensor array can improve measurement accuracy and obtain a reliable initial meteorological humidity data, while the multi-sensor data fusion technique eliminates the uncertainty in the measurement. The radiosonde can accurately reflect the meteorological changes.

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.

Dithiobis(succinimidyl propionate) modified gold microarray electrode based electrochemical immunosensor for ultrasensitive detection of cortisol.

PubMed

Arya, Sunil K; Chornokur, Ganna; Venugopal, Manju; Bhansali, Shekhar

2010-06-15

Gold microelectrode arrays functionalized with dithiobis(succinimidyl propionate) self-assembled monolayer (SAM) have been used to fabricate an ultrasensitive, disposable, electrochemical cortisol immunosensor. Cortisol specific monoclonal antibody (C-Mab) was covalently immobilized on the surface of gold microelectrode array and the sensors were exposed to solutions with different cortisol concentration. After C-Mab binding, unreacted active groups of DTSP were blocked using ethanol amine (EA) and label-free electrochemical impedance (EIS) technique was used to determine cortisol concentration. EIS results confirmed that EA/C-Mab/DTSP/Au based biosensor can accurately detect cortisol in the range of 1pM-100nM. The biosensor was successfully used for the measurement of cortisol in interstitial fluid in vitro. This research establishes the feasibility of using impedance based biosensor architecture for disposable, wearable cortisol detector. Copyright 2010 Elsevier B.V. All rights reserved.

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

PubMed

Manyakov, Nikolay V; Van Hulle, Marc M

2010-04-01

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

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

In Vitro Studies of Neuronal Networks and Synaptic Plasticity in Invertebrates and in Mammals Using Multielectrode Arrays

PubMed Central

Tessadori, Jacopo; Ghirardi, Mirella

2015-01-01

Brain functions are strictly dependent on neural connections formed during development and modified during life. The cellular and molecular mechanisms underlying synaptogenesis and plastic changes involved in learning and memory have been analyzed in detail in simple animals such as invertebrates and in circuits of mammalian brains mainly by intracellular recordings of neuronal activity. In the last decades, the evolution of techniques such as microelectrode arrays (MEAs) that allow simultaneous, long-lasting, noninvasive, extracellular recordings from a large number of neurons has proven very useful to study long-term processes in neuronal networks in vivo and in vitro. In this work, we start off by briefly reviewing the microelectrode array technology and the optimization of the coupling between neurons and microtransducers to detect subthreshold synaptic signals. Then, we report MEA studies of circuit formation and activity in invertebrate models such as Lymnaea, Aplysia, and Helix. In the following sections, we analyze plasticity and connectivity in cultures of mammalian dissociated neurons, focusing on spontaneous activity and electrical stimulation. We conclude by discussing plasticity in closed-loop experiments. PMID:25866681

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.

Development of biosensors for non-invasive measurements of heart failure biomarkers in saliva

NASA Astrophysics Data System (ADS)

Alcacer, Albert; Streklas, Angelos; Baraket, Abdoullatif; Zine, Nadia; Errachid, Abdelhamid; Bausells, Joan

2017-06-01

Biomedical engineering research today is focused on non-invasive techniques for detection of biomarkers related to specific health issues 1. Three metal layer microelectrode (μE) sensors have been implemented to detect specific biomarkers which can be found in human saliva related with heart failure problems 2 such as interleukin and Tumore Necrosis Factor-α (TNF-α), and used as highly sensitive saliva sensors. We designed specialized μEs combining different technologies for multiple measurements aiming to a lab-on-a-chip future integration. Measurements are based to basic principles of Cyclic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS). Thus, certain planar technology was used involving three metal layers of gold, platinum and silver deposited over an oxidized silicon substrate following standard cleanroom procedures of lithography for the definition of μEs, sputtering physical vapor deposition (PVD) for gold, evaporation PVD for silver and platinum, and plasma enhanced chemical vapor deposition (PECVD) for passivation layer of silicon nitride.

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.

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.

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

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

PubMed

Salari, A; Navi, M; Dalton, C

2015-01-01

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

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.

The use of optical fiber bundles combined with electrochemistry for chemical imaging.

PubMed

Szunerits, Sabine; Walt, David R

2003-02-17

The present Review describes the progress made in using imaging optical fiber bundles for fluorescence and electrochemical-initiated chemiluminescence imaging. A novel optoelectrochemical micro-ring array has been fabricated and demonstrated for concurrent electrochemical and optical measurements. The device comprises optical fibers coated with gold via electroless gold deposition and assembled in a random array format. The design yielded an array of approximately 200 micro-ring electrodes, where interdiffusional problems were minimized. The inner diameter of the ring electrode is fixed by the diameter of the individual optical fibers (25 microns), while the outer radius is determined by the thickness of the deposited gold. While all the fibers are optically addressable, they are not all electrochemically addressable. The resolution of this device is in the tens of micrometers range, determined by the diameter of the optical fiber (25 microns) and by the spacing between each electrically connected fiber. For the purpose of having well-behaved microelectrode characteristics, this spacing was designed to be larger than 60 microns. The array was characterized using ferrocyanide in aqueous solution as a model electroactive species to demonstrate that this microelectrode array format exhibits steady-state currents at short response times. This device has potential application to be used as an optoelectronic sensor, especially for the electrolytic generation and transmission of electrochemiluminescence, and was used to demonstrate that electrochemically generated luminescent products can be detected with the fiber assembly.

Density controlled carbon nanotube array electrodes

DOEpatents

Ren, Zhifeng F [Newton, MA; Tu, Yi [Belmont, MA

2008-12-16

CNT materials comprising aligned carbon nanotubes (CNTs) with pre-determined site densities, catalyst substrate materials for obtaining them and methods for forming aligned CNTs with controllable densities on such catalyst substrate materials are described. The fabrication of films comprising site-density controlled vertically aligned CNT arrays of the invention with variable field emission characteristics, whereby the field emission properties of the films are controlled by independently varying the length of CNTs in the aligned array within the film or by independently varying inter-tubule spacing of the CNTs within the array (site density) are disclosed. The fabrication of microelectrode arrays (MEAs) formed utilizing the carbon nanotube material of the invention is also described.

Lead field theory provides a powerful tool for designing microelectrode array impedance measurements for biological cell detection and observation.

PubMed

Böttrich, Marcel; Tanskanen, Jarno M A; Hyttinen, Jari A K

2017-06-26

Our aim is to introduce a method to enhance the design process of microelectrode array (MEA) based electric bioimpedance measurement systems for improved detection and viability assessment of living cells and tissues. We propose the application of electromagnetic lead field theory and reciprocity for MEA design and measurement result interpretation. Further, we simulated impedance spectroscopy (IS) with two- and four-electrode setups and a biological cell to illustrate the tool in the assessment of the capabilities of given MEA electrode constellations for detecting cells on or in the vicinity of the microelectrodes. The results show the power of the lead field theory in electromagnetic simulations of cell-microelectrode systems depicting the fundamental differences of two- and four-electrode IS measurement configurations to detect cells. Accordingly, the use in MEA system design is demonstrated by assessing the differences between the two- and four-electrode IS configurations. Further, our results show how cells affect the lead fields in these MEA system, and how we can utilize the differences of the two- and four-electrode setups in cell detection. The COMSOL simulator model is provided freely in public domain as open source. Lead field theory can be successfully applied in MEA design for the IS based assessment of biological cells providing the necessary visualization and insight for MEA design. The proposed method is expected to enhance the design and usability of automated cell and tissue manipulation systems required for bioreactors, which are intended for the automated production of cell and tissue grafts for medical purposes. MEA systems are also intended for toxicology to assess the effects of chemicals on living cells. Our results demonstrate that lead field concept is expected to enhance also the development of such methods and devices.

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

Novel quantitative methods for characterization of chemical induced functional alteration in developing neuronal cultures

EPA Science Inventory

ABSTRACT BODY: Thousands of chemicals lack adequate testing for adverse effects on nervous system development, stimulating research into alternative methods to screen chemicals for potential developmental neurotoxicity. Microelectrode arrays (MEA) collect action potential spiking...

Arrays of Very Small Voltammetric Electrodes Based on Reticulated Vitreous Carbon.

DTIC Science & Technology

1983-10-14

1H D-fli34 73ifARRAYS OF VERY SMALL YOLTAMMETRIC ELECTRODES BA5ED ON i/i RETICULATED VITREOUS CARBON (U) STATE UNIV OF NEW YORK I AT BUFFALO AMHERST N...PEIOiUD COVI[R9 1^. Arrays of Very Small Voltametric Electrodes 0 Based on Reticulated Vitreous Carbon - S. PRFROG OG. REPORT NUM A 7. AUTNOR) 0...Cofigi nueu eav’e,o *ee i necesaery and Iden lly by block number) L.Uj Reticulated vitreous carbon ; microelectrodes; nonlinear diffusion; vol tammetry

A novel high electrode count spike recording array using an 81,920 pixel transimpedance amplifier-based imaging chip.

PubMed

Johnson, Lee J; Cohen, Ethan; Ilg, Doug; Klein, Richard; Skeath, Perry; Scribner, Dean A

2012-04-15

Microelectrode recording arrays of 60-100 electrodes are commonly used to record neuronal biopotentials, and these have aided our understanding of brain function, development and pathology. However, higher density microelectrode recording arrays of larger area are needed to study neuronal function over broader brain regions such as in cerebral cortex or hippocampal slices. Here, we present a novel design of a high electrode count picocurrent imaging array (PIA), based on an 81,920 pixel Indigo ISC9809 readout integrated circuit camera chip. While originally developed for interfacing to infrared photodetector arrays, we have adapted the chip for neuron recording by bonding it to microwire glass resulting in an array with an inter-electrode pixel spacing of 30 μm. In a high density electrode array, the ability to selectively record neural regions at high speed and with good signal to noise ratio are both functionally important. A critical feature of our PIA is that each pixel contains a dedicated low noise transimpedance amplifier (∼0.32 pA rms) which allows recording high signal to noise ratio biocurrents comparable to single electrode voltage amplifier recordings. Using selective sampling of 256 pixel subarray regions, we recorded the extracellular biocurrents of rabbit retinal ganglion cell spikes at sampling rates up to 7.2 kHz. Full array local electroretinogram currents could also be recorded at frame rates up to 100 Hz. A PIA with a full complement of 4 readout circuits would span 1cm and could acquire simultaneous data from selected regions of 1024 electrodes at sampling rates up to 9.3 kHz. Published by Elsevier B.V.

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...

Screening for Developmental Neurotoxicants using In Vitro "Brain on a Chip" Cultures

EPA Science Inventory

Currently there are thousands of chemicals in the environment that have not been screened for their potential to cause developmental neurotoxicity (DNT). The use of microelectrode array (MEA) technology allows for simultaneous extracellular measurement of action potential (spike)...

The Promise of Microelectrode Array Approaches for Toxicity Testing: Examples with Neuroactive Chemicals

EPA Science Inventory

While high-throughput patch clamping formats provide rapid characterization of chemical effects on ion channel function and kinetics, the limitations of such systems often include the need for channel by channel characterization, requirements for transfected, rather than primary ...

Silver Nanoparticles and Ionic Silver Have Opposite Effects on Spontaneous Activity and Pharmacological Responses in Neuronal Networks In Vitro

EPA Science Inventory

CONTROL ID: 1850472 CONTACT (NAME ONLY): Timothy Shafer Abstract Details PRESENTATION TYPE: Platform or Poster CURRENT CATEGORY: Nanotoxicology, In Vitro | Neurotoxicity, General | Neurotoxicity, Metals KEYWORDS: Nanoparticle, Neurotoxicity, microelectrode array. DATE/TIME LAST...

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

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.

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.

Effects of an Environmentally-relevant Mixture of Pyrethroid Insecticides on Spontaneous Activity in Primary Cortical Networks on Microelectrode Arrays

EPA Science Inventory

Pyrethroid insecticides exert their insecticidal and toxicological effects primarily by disrupting voltage-gated sodium channel (VGSC) function, resulting in altered neuronal excitability. Numerous studies of individual pyrethroids have characterized effects on mammalian VGSC fun...

Boron-doped nanocrystalline diamond microelectrode arrays monitor cardiac action potentials.

PubMed

Maybeck, Vanessa; Edgington, Robert; Bongrain, Alexandre; Welch, Joseph O; Scorsone, Emanuel; Bergonzo, Philippe; Jackman, Richard B; Offenhäusser, Andreas

2014-02-01

The expansion of diamond-based electronics in the area of biological interfacing has not been as thoroughly explored as applications in electrochemical sensing. However, the biocompatibility of diamond, large safe electrochemical window, stability, and tunable electronic properties provide opportunities to develop new devices for interfacing with electrogenic cells. Here, the fabrication of microelectrode arrays (MEAs) with boron-doped nanocrystalline diamond (BNCD) electrodes and their interfacing with cardiomyocyte-like HL-1 cells to detect cardiac action potentials are presented. A nonreductive means of structuring doped and undoped diamond on the same substrate is shown. The resulting BNCD electrodes show high stability under mechanical stress generated by the cells. It is shown that by fabricating the entire surface of the MEA with NCD, in patterns of conductive doped, and isolating undoped regions, signal detection may be improved up to four-fold over BNCD electrodes passivated with traditional isolators. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Brain computer interface learning for systems based on electrocorticography and intracortical microelectrode arrays.

PubMed

Hiremath, Shivayogi V; Chen, Weidong; Wang, Wei; Foldes, Stephen; Yang, Ying; Tyler-Kabara, Elizabeth C; Collinger, Jennifer L; Boninger, Michael L

2015-01-01

A brain-computer interface (BCI) system transforms neural activity into control signals for external devices in real time. A BCI user needs to learn to generate specific cortical activity patterns to control external devices effectively. We call this process BCI learning, and it often requires significant effort and time. Therefore, it is important to study this process and develop novel and efficient approaches to accelerate BCI learning. This article reviews major approaches that have been used for BCI learning, including computer-assisted learning, co-adaptive learning, operant conditioning, and sensory feedback. We focus on BCIs based on electrocorticography and intracortical microelectrode arrays for restoring motor function. This article also explores the possibility of brain modulation techniques in promoting BCI learning, such as electrical cortical stimulation, transcranial magnetic stimulation, and optogenetics. Furthermore, as proposed by recent BCI studies, we suggest that BCI learning is in many ways analogous to motor and cognitive skill learning, and therefore skill learning should be a useful metaphor to model BCI learning.

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.

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.

Continuous separation of colloidal particles using dielectrophoresis.

PubMed

Yunus, Nurul Amziah Md; Nili, Hossein; Green, Nicolas G

2013-04-01

Dielectrophoresis is the movement of particles in nonuniform electric fields and has been of interest for application to manipulation and separation at and below the microscale. This technique has the advantages of being noninvasive, nondestructive, and noncontact, with the movement of particle achieved by means of electric fields generated by miniaturized electrodes and microfluidic systems. Although the majority of applications have been above the microscale, there is increasing interest in application to colloidal particles around a micron and smaller. This paper begins with a review of colloidal and nanoscale dielectrophoresis with specific attention paid to separation applications. An innovative design of integrated microelectrode array and its application to flow-through, continuous separation of colloidal particles is then presented. The details of the angled chevron microelectrode array and the test microfluidic system are then discussed. The variation in device operation with applied signal voltage is presented and discussed in terms of separation efficiency, demonstrating 99.9% separation of a mixture of colloidal latex spheres. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Substrate dependent stability of conducting polymer coatings on medical electrodes.

PubMed

Green, Rylie A; Hassarati, Rachelle T; Bouchinet, Lucie; Lee, Chaekyung S; Cheong, Gin L M; Yu, Jin F; Dodds, Christopher W; Suaning, Gregg J; Poole-Warren, Laura A; Lovell, Nigel H

2012-09-01

Conducting polymer (CP) coatings on medical electrodes have the potential to provide superior performance when compared to conventional metallic electrodes, but their stability is strongly dependant on the substrate properties. The aim of this study was to examine the effect of laser roughening of underlying platinum (Pt) electrode surfaces on the mechanical, electrical and biological performance of CP coatings. In addition, the impact of dopant type on electrical performance and stability was assessed. The CP poly(ethylene dioxythiophene) (PEDOT) was coated on Pt microelectrode arrays, with three conventional dopant ions. The in vitro electrical characteristics were assessed by cyclic voltammetry and biphasic stimulation. Results showed that laser roughening of the underlying substrate did not affect the charge injection limit of the coated material, but significantly improved the passive stability and chronic stimulation lifetime without failure of the coating. Accelerated material ageing and long-term biphasic stimulus studies determined that some PEDOT variants experienced delamination within as little as 10 days when the underlying Pt was smooth, but laser roughening to produce a surface index of 2.5 improved stability, such that more than 1.3 billion stimulation cycles could be applied without evidence of failure. PEDOT doped with paratoluene sulfonate (PEDOT/pTS) was found to be the most stable CP on roughened Pt, and presented a surface topography which encouraged neural cell attachment. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

In vitro cyto-biocompatibility study of thin-film transistors substrates using an organotypic culture method.

PubMed

Leclerc, Eric; Duval, Jean-Luc; Egles, Christophe; Ihida, Satoshi; Toshiyoshi, Hiroshi; Tixier-Mita, Agnès

2017-01-01

Thin-Film-Transistors Liquid-Crystal Display has become a standard in the field of displays. However, the structure of these devices presents interest not only in that field, but also for biomedical applications. One of the key components, called here TFT substrate, is a glass substrate with a dense and large array of thousands of transparent micro-electrodes that can be considered as a large scale multi-electrode array(s). Multi-electrode array(s) are widely used for in vitro electrical investigations on neurons and brain, allowing excitation, registration, and recording of their activity. However, the range of application of conventional multi-electrode array(s) is usually limited to some tens of cells in a homogeneous cell culture, because of a small area, small number and a low density of the micro-electrodes. TFT substrates do not have these limitations and the authors are currently studying the possibility to use TFT substrates as new tools for in vitro electrical investigation on tissues and organoids. In this respect, experiments to determine the cyto-biocompatibility of TFT substrates with tissues were conducted and are presented in this study. The investigation was performed using an organotypic culture method with explants of brain and liver tissues of chick embryos. The results in term of morphology, cell migration, cell density and adhesion were compared with the results from Thermanox ® , a conventional plastic for cell culture, and with polydimethylsiloxane, a hydrophobic silicone. The results with TFT substrates showed similar results as for the Thermanox ® , despite the TFT hydrophobicity. TFT substrates have a weak cell adhesion and promote cell migration similarly to Thermanox ® . It could be concluded that the TFT substrates are cyto-biocompatible with the two studied organs.

Theoretical Model of Electrode Polarization and AC Electroosmotic Fluid Flow in Planar Electrode Arrays.

PubMed

Scott, Matthew; Kaler, Karan V. I. S.; Paul, Reginald

2001-06-15

Strong frequency-dependent fluid flow has been observed near the surface of microelectrode arrays. Modeling this phenomenon has proven to be difficult, with existing theories unable to account for the qualitative trend observed in the frequency spectra of this flow. Using recent electrode polarization results, a more comprehensive model of the double layer on the electrode surface is used to obtain good theoretical agreement with experimental data. Copyright 2001 Academic Press.

IN VITRO ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY: USE OF MICROELECTRODE ARRAYS TO MEASURE FUNCTIONAL CHANGES IN NEURONAL NETWORK ONTOGENY

EPA Science Inventory

Because the Developmental Neurotoxicity Testing Battery requires large numbers of animals and is expensive, development of in vitro approaches to screen chemicals for potential developmental neurotoxicity is a high priority. Many proposed approaches for screening are biochemical,...

In Vitro Assessment of Developmental Neurotoxicity: Use of Microelectrode Arrays to Measure Functional Changes in Neuronal Network Ontogeny*

EPA Science Inventory

Because the Developmental Neurotoxicity Testing Guidelines require large numbers of animals and is expensive, development of in vitro approaches to screen chemicals for potential developmental neurotoxicity is a high priority. Many proposed approaches for screening are biochemica...

Development of micro-electrode array based tests for neurotoxicity: assessment of interlaboratory reproducibility with neuroactive chemicals

EPA Science Inventory

Neuronal assemblies within the Central Nervous System (CNS) produce spontaneous or stimulus-evoked electrophysiological activity that can be monitored and quantified in terms of action potential patterns. Such patterns provide a sensitive endpoint to detect effects of chemicals, ...

Low and High-Frequency Field Potentials of Cortical Networks Exhibit Distinct Responses to Chemicals

EPA Science Inventory

Neural networks grown on microelectrode arrays (MEAs) have become an important, high content in vitro assay for assessing neuronal function. MEA experiments typically examine high- frequency (HF) (>200 Hz) spikes, and bursts which can be used to discriminate between differ...

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.

Investigation of the oxygen exchange mechanism on Pt|yttria stabilized zirconia at intermediate temperatures: Surface path versus bulk path

PubMed Central

Opitz, Alexander K.; Lutz, Alexander; Kubicek, Markus; Kubel, Frank; Hutter, Herbert; Fleig, Jürgen

2011-01-01

The oxygen exchange kinetics of platinum on yttria-stabilized zirconia (YSZ) was investigated by means of geometrically well-defined Pt microelectrodes. By variation of electrode size and temperature it was possible to separate two temperature regimes with different geometry dependencies of the polarization resistance. At higher temperatures (550–700 °C) an elementary step located close to the three phase boundary (TPB) with an activation energy of ∼1.6 eV was identified as rate limiting. At lower temperatures (300–400 °C) the rate limiting elementary step is related to the electrode area and exhibited a very low activation energy in the order of 0.2 eV. From these observations two parallel pathways for electrochemical oxygen exchange are concluded. The nature of these two elementary steps is discussed in terms of equivalent circuits. Two combinations of parallel rate limiting reaction steps are found to explain the observed geometry dependencies: (i) Diffusion through an impurity phase at the TPB in parallel to diffusion of oxygen through platinum – most likely along Pt grain boundaries – as area-related process. (ii) Co-limitation of oxygen diffusion along the Pt|YSZ interface and charge transfer at the interface with a short decay length of the corresponding transmission line (as TPB-related process) in parallel to oxygen diffusion through platinum. PMID:22210951

Generation of patterned cell co-cultures in silicone tubing using a microelectrode technique and electrostatic assembly.

PubMed

Kaji, Hirokazu; Sekine, Soichiro; Hashimoto, Masahiko; Kawashima, Takeaki; Nishizawa, Matsuhiko

2007-01-01

We report a method for producing patterned cell adhesion inside silicone tubing. A platinum needle microelectrode was inserted through the wall of the tubing and an oxidizing agent electrochemically generated at the inserted electrode. This agent caused local detachment of the anti-biofouling heparin layer from the inner surface of the tubing. The cell-adhesive protein fibronectin selectively adsorbed onto the newly exposed surface, making it possible to initiate a localized cell culture. The electrode could be readily set in place without breaking the tubular structure and, importantly, almost no culture solution leaked from the electrode insertion site after the electrode was removed. Ionic adsorption of poly-L-lysine at the tubular region retaining a heparin coating was used to switch the heparin surface from cell-repellent to cell-adhesive, thereby facilitating the adhesion of a second cell type. The combination of the electrode-based technique with electrostatic deposition enabled the formation of patterned co-cultures within the semi-closed tubular structure. The controlled co-cultures inside the elastic tubing should be of value for cell-cell interaction studies following application of chemical or mechanical stimuli and for tissue engineering-based bioreactors.

In-vivo electrochemical monitoring of H2O2 production induced by root-inoculated endophytic bacteria in Agave tequilana leaves.

PubMed

Lima, Alex S; Prieto, Kátia R; Santos, Carla S; Paula Valerio, Hellen; Garcia-Ochoa, Evelyn Y; Huerta-Robles, Aurora; Beltran-Garcia, Miguel J; Di Mascio, Paolo; Bertotti, Mauro

2018-01-15

A dual-function platinum disc microelectrode sensor was used for in-situ monitoring of H 2 O 2 produced in A. tequilana leaves after inoculation of their endophytic bacteria (Enterobacter cloacae). Voltammetric experiments were carried out from 0.0 to -1.0V, a potential range where H 2 O 2 is electrochemically reduced. A needle was used to create a small cavity in the upper epidermis of A. tequilana leaves, where the fabricated electrochemical sensor was inserted by using a manual three-dimensional micropositioner. Control experiments were performed with untreated plants and the obtained electrochemical results clearly proved the formation of H 2 O 2 in the leaves of plants 3h after the E. cloacae inoculation, according to a mechanism involving endogenous signaling pathways. In order to compare the sensitivity of the microelectrode sensor, the presence of H 2 O 2 was detected in the root hairs by 3,3-diaminobenzidine (DAB) stain 72h after bacterial inoculation. In-situ pH measurements were also carried out with a gold disc microelectrode modified with a film of iridium oxide and lower pH values were found in A. tequilana leaves treated with bacteria, which may indicate the plant produces acidic substances by biosynthesis of secondary metabolites. This microsensor could be an advantageous tool for further studies on the understanding of the mechanism of H 2 O 2 production during the plant-endophyte interaction. Copyright © 2017 Elsevier B.V. All rights reserved.

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 Reconstitution of Biomolecules for Applications as Electrocatalysts for the Bionanofuel Cell

NASA Technical Reports Server (NTRS)

Kim, Jae-Woo; Choi, Sang H.; Lillehei, Peter T.; King, Glen C.; Watt, Gerald D.; Chu, Sang-Hyon; Park, Yeonjoon; Thibeault, Sheila

2004-01-01

Platinum-cored ferritins were synthesized as electrocatalysts by electrochemical biomineralization of immobilized apoferritin with platinum. The platinum cored ferritin was fabricated by exposing the immobilized apoferritin to platinum ions at a reduction potential. On the platinum-cored ferritin, oxygen is reduced to water with four protons and four electrons generated from the anode. The ferritin acts as a nano-scale template, a biocompatible cage, and a separator between the nanoparticles. This results in a smaller catalyst loading of the electrodes for fuel cells or other electrochemical devices. In addition, the catalytic activity of the ferritin-stabilized platinum nanoparticles is enhanced by the large surface area and particle size phenomena. The work presented herein details the immobilization of ferritin with various surface modifications, the electrochemical biomineralization of ferritin with different inorganic cores, and the fabrication of self-assembled 2-D arrays with thiolated ferritin.

Large-format platinum silicide microwave kinetic inductance detectors for optical to near-IR astronomy.

PubMed

Szypryt, P; Meeker, S R; Coiffard, G; Fruitwala, N; Bumble, B; Ulbricht, G; Walter, A B; Daal, M; Bockstiegel, C; Collura, G; Zobrist, N; Lipartito, I; Mazin, B A

2017-10-16

We have fabricated and characterized 10,000 and 20,440 pixel Microwave Kinetic Inductance Detector (MKID) arrays for the Dark-speckle Near-IR Energy-resolved Superconducting Spectrophotometer (DARKNESS) and the MKID Exoplanet Camera (MEC). These instruments are designed to sit behind adaptive optics systems with the goal of directly imaging exoplanets in a 800-1400 nm band. Previous large optical and near-IR MKID arrays were fabricated using substoichiometric titanium nitride (TiN) on a silicon substrate. These arrays, however, suffered from severe non-uniformities in the TiN critical temperature, causing resonances to shift away from their designed values and lowering usable detector yield. We have begun fabricating DARKNESS and MEC arrays using platinum silicide (PtSi) on sapphire instead of TiN. Not only do these arrays have much higher uniformity than the TiN arrays, resulting in higher pixel yields, they have demonstrated better spectral resolution than TiN MKIDs of similar design. PtSi MKIDs also do not display the hot pixel effects seen when illuminating TiN on silicon MKIDs with photons with wavelengths shorter than 1 µm.

Editor's highlight: Evaluation of a Microelectrode Array-based Assay for Neural Network Ontogeny using Training Set Chemicals

EPA Science Inventory

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...

Burst and Principal Components Analyses of MEA Data for 16 Chemicals Describe at Least Three Effects Classes.

EPA Science Inventory

Microelectrode arrays (MEAs) detect drug and chemical induced changes in neuronal network function and have been used for neurotoxicity screening. As a proof-•of-concept, the current study assessed the utility of analytical "fingerprinting" using Principal Components Analysis (P...

Single Cell Oxygen Mapping (SCOM) by Scanning Electrochemical Microscopy Uncovers Heterogeneous Intracellular Oxygen Consumption.

PubMed

Santos, Carla Santana; Kowaltowski, Alicia J; Bertotti, Mauro

2017-09-12

We developed a highly sensitive oxygen consumption scanning microscopy system using platinized platinum disc microelectrodes. The system is capable of reliably detecting single-cell respiration, responding to classical regulators of mitochondrial oxygen consumption activity as expected. Comparisons with commercial multi-cell oxygen detection systems show that the system has comparable errors (if not smaller), with the advantage of being able to monitor inter and intra-cell heterogeneity in oxygen consumption characteristics. Our results uncover heterogeneous oxygen consumption characteristics between cells and within the same cell´s microenvironments. Single Cell Oxygen Mapping (SCOM) is thus capable of reliably studying mitochondrial oxygen consumption characteristics and heterogeneity at a single-cell level.

Evaluation of Microelectrode Array Data using Bayesian Modeling as an Approach to Screening and Prioritization for Neurotoxicity Testing*

EPA Science Inventory

The need to assess large numbers of chemicals for their potential toxicities has resulted in increased emphasis on medium- and high-throughput in vitro screening approaches. For such approaches to be useful, efficient and reliable data analysis and hit detection methods are also ...

Using developing cortical cultures on microelectrode arrays to identify and prioritize compounds based on changes in network formation

EPA Science Inventory

Characterization of the potential adverse effects is lacking for tens of thousands of chemicals that are present in the environment, and characterization of developmental neurotoxicity (DNT) hazard lags behind that of other adverse outcomes (e.g. hepatotoxicity). This is due in p...

Alternative Post-Processing on a CMOS Chip to Fabricate a Planar Microelectrode Array

PubMed Central

López-Huerta, Francisco; Herrera-May, Agustín L.; Estrada-López, Johan J.; Zuñiga-Islas, Carlos; Cervantes-Sanchez, Blanca; Soto, Enrique; Soto-Cruz, Blanca S.

2011-01-01

We present an alternative post-processing on a CMOS chip to release a planar microelectrode array (pMEA) integrated with its signal readout circuit, which can be used for monitoring the neuronal activity of vestibular ganglion neurons in newborn Wistar strain rats. This chip is fabricated through a 0.6 μm CMOS standard process and it has 12 pMEA through a 4 × 3 electrodes matrix. The alternative CMOS post-process includes the development of masks to protect the readout circuit and the power supply pads. A wet etching process eliminates the aluminum located on the surface of the p+-type silicon. This silicon is used as transducer for recording the neuronal activity and as interface between the readout circuit and neurons. The readout circuit is composed of an amplifier and tunable bandpass filter, which is placed on a 0.015 mm2 silicon area. The tunable bandpass filter has a bandwidth of 98 kHz and a common mode rejection ratio (CMRR) of 87 dB. These characteristics of the readout circuit are appropriate for neuronal recording applications. PMID:22346681

Alternative post-processing on a CMOS chip to fabricate a planar microelectrode array.

PubMed

López-Huerta, Francisco; Herrera-May, Agustín L; Estrada-López, Johan J; Zuñiga-Islas, Carlos; Cervantes-Sanchez, Blanca; Soto, Enrique; Soto-Cruz, Blanca S

2011-01-01

We present an alternative post-processing on a CMOS chip to release a planar microelectrode array (pMEA) integrated with its signal readout circuit, which can be used for monitoring the neuronal activity of vestibular ganglion neurons in newborn Wistar strain rats. This chip is fabricated through a 0.6 μm CMOS standard process and it has 12 pMEA through a 4 × 3 electrodes matrix. The alternative CMOS post-process includes the development of masks to protect the readout circuit and the power supply pads. A wet etching process eliminates the aluminum located on the surface of the p+ -type silicon. This silicon is used as transducer for recording the neuronal activity and as interface between the readout circuit and neurons. The readout circuit is composed of an amplifier and tunable bandpass filter, which is placed on a 0.015 mm2 silicon area. The tunable bandpass filter has a bandwidth of 98 kHz and a common mode rejection ratio (CMRR) of 87 dB. These characteristics of the readout circuit are appropriate for neuronal recording applications.

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.

Laser micromachining of biofactory-on-a-chip devices

NASA Astrophysics Data System (ADS)

Burt, Julian P.; Goater, Andrew D.; Hayden, Christopher J.; Tame, John A.

2002-06-01

Excimer laser micromachining provides a flexible means for the manufacture and rapid prototyping of miniaturized systems such as Biofactory-on-a-Chip devices. Biofactories are miniaturized diagnostic devices capable of characterizing, manipulating, separating and sorting suspension of particles such as biological cells. Such systems operate by exploiting the electrical properties of microparticles and controlling particle movement in AC non- uniform stationary and moving electric fields. Applications of Biofactory devices are diverse and include, among others, the healthcare, pharmaceutical, chemical processing, environmental monitoring and food diagnostic markets. To achieve such characterization and separation, Biofactory devices employ laboratory-on-a-chip type components such as complex multilayer microelectrode arrays, microfluidic channels, manifold systems and on-chip detection systems. Here we discuss the manufacturing requirements of Biofactory devices and describe the use of different excimer laser micromachined methods both in stand-alone processes and also in conjunction with conventional fabrication processes such as photolithography and thermal molding. Particular attention is given to the production of large area multilayer microelectrode arrays and the manufacture of complex cross-section microfluidic channel systems for use in simple distribution and device interfacing.

Hybrid electronic tongue based on optical and electrochemical microsensors for quality control of wine.

PubMed

Gutiérrez, Manuel; Llobera, Andreu; Vila-Planas, Jordi; Capdevila, Fina; Demming, Stefanie; Büttgenbach, Stephanus; Mínguez, Santiago; Jiménez-Jorquera, Cecilia

2010-07-01

A multiparametric system able to classify red and white wines according to the grape varieties and for analysing some specific parameters is presented. The system, known as hybrid electronic tongue, consists of an array of electrochemical microsensors and a colorimetric optofluidic system. The array of electrochemical sensors is composed of six ISFETs based sensors, a conductivity sensor, a redox potential sensor and two amperometric electrodes, an Au microelectrode and a microelectrode for sensing electrochemical oxygen demand. The optofluidic system is entirely fabricated in polymer technology and comprises a hollow structure, air mirrors, microlenses and self-alignment structures. The data obtained from these sensors has been treated with multivariate advanced tools; Principal Component Analysis (PCA), for the patterning recognition and classification of wine samples, and Partial-Least Squares (PLS) regression, for quantification of several chemical and optical parameters of interest in wine quality. The results have demonstrated the utility of this system for distinguishing the samples according to the grape variety and year vintage and for quantifying several sample parameters of interest in wine quality control.

iCELLigence real-time cell analysis system for examining the cytotoxicity of drugs to cancer cell lines

PubMed Central

Türker Şener, Leyla; Albeni̇z, Gürcan; Di̇nç, Bi̇rcan; Albeni̇z, Işil

2017-01-01

The recently developed iCELLigence™ real-time cell analyzer (RTCA) can be used for the label-free real-time monitoring of cancer cell proliferation, viability, invasion and cytotoxicity. The RTCA system uses 16-well microtiter plates with a gold microelectrode biosensor array that measures impedance when cells adhere to the microelectrodes causing an alternating current. By measuring the electric field generated in this process, the RTCA system can be used for the analysis of cell proliferation, viability, morphology and migration. The present review aimed to summarize the working method of the RTCA system, in addition to discussing the research performed using the system for various applications, including cancer drug discovery via measuring cytotoxicity. PMID:28962095

Two-phase interdigitated microelectrode arrays for electrokinetic transport of microparticles

NASA Astrophysics Data System (ADS)

Bligh, Mathew; Stanley, Kevin G.; Hubbard, Ted; Kujath, Marek

2008-05-01

In this paper, we demonstrate long-range particle transport using linear two-phase interdigitated arrays with electrodes of equal size but with asymmetric spacing between them. We report net motion of 6 µm polystyrene spheres in an aqueous electrolyte and characterize the dependence of particle velocity on frequency, potential and phase, and show consistency with previous experiments that involved four-phase arrays producing AC electroosmotic and dielectrophoretic forces. We explore the effect of increasing the asymmetry of the electrode spacing and show that this decreases the performance of the array. We also examine the effect of increasing the overall scale of the array while maintaining geometric proportions and particle size and report that this also decreases the performance. We compare our results to previous analytical theoretical predictions and find general agreement.

An impedimetric micro-immunosensing assay to detect Alzheimer's disease biomarker: Aβ40.

PubMed

Zakaria, Norazreen; Ramli, Muhammad Zaki; Ramasamy, Kalavathy; Meng, Lim Siong; Yean, Chan Yean; Banga Singh, Kirnpal Kaur; Zain, Zainiharyati Mohd; Low, Kim-Fatt

2018-06-04

A miniaturized biosensing platform, based on monoclonal amyloid-beta antibodies (mAβ ab ) that were immobilized on a disc-shaped platinum/iridium (Pt/Ir) microelectrode surface coupled with an impedimetric signal transducer, was developed for the label-free and sensitive detection of amyloid-beta peptide fragment 1-40 (Aβ40); a reliable biomarker for early diagnosis of Alzheimer's disease (AD). A Pt/Ir microelectrode was electropolymerized with poly (ortho-phenylenediamine), a conducting free amine-containing aromatic polymer; followed by crosslinking with glutaraldehyde for subsequent coupling of mAβ ab on the microelectrode surface. This modification strategy efficiently improved the impedimetric detection performance of Aβ40 in terms of charge transfer resistance (∼400-fold difference) and normalized impedance magnitude percentage change (∼40% increase) compared with a passive adsorption-based immobilization method. The sensitivity of the micro-immunosensing assay was found to be 1056 kΩ/(pg/mL)/cm 2 and the limit of detection was found to be 4.81 pg/mL with a dynamic range of 1-10 4  pg/mL (R 2  = 0.9932). The overall precision of the assay, as measured by relative standard deviation, ranged from 0.84 to 5.15%, demonstrating its reliability and accuracy; while in respect to assay durability and stability, the immobilized mAβ ab were able to maintain 80% of their binding activity to Aβ40 after incubation for 48 h at ambient temperature (25 °C). To validate the practical applicability, the assay was tested using brain tissue lysates prepared from AD-induced rats. Results indicate that the proposed impedimetric micro-immunosensing platform is highly versatile and adaptable for the quantitative detection of other disease-related biomarkers. Copyright © 2018 Elsevier Inc. All rights reserved.

Enzyme-coated microelectrodes to monitor lactate production in a nanoliter microfluidic cell culture device

PubMed Central

Ges, Igor A.; Baudenbacher, Franz

2015-01-01

Monitoring the degree of anaerobic respiration of cells in high density microscale culture systems is an enabling key technology and essential for cell-based biosensors. We have fabricated and incorporated miniature amperometric lactate sensing electrodes with working areas from 3 to 5×10−2 mm2 into a microfluidic-based microscale cell culture system to measure the lactate production rate of fibroblasts in nanoliter volumes. Planar thin film platinum electrode arrays on glass substrates were spin coated with lactate oxidase and a protective Nafion layer. The lactate electrodes had a high enzymatic activity described by a Michaelis-Menten constant of 2.6±0.1 mM, a linear response in the range 0.01÷2.5mM and a sensitivity of 7.3×10−2mA/mM·cm2. A replica-molded polydimethylsiloxane (PDMS) microfluidic device with nanoliter sensing volumes was aligned and sealed to a glass substrate with the sensing electrodes. We trapped fibroblasts in the cell culture volume and measured the lactate production rate using a stop and flow protocol. The average lactate production rate was 0.011±0.0049mM/min. The lactate production was suppressed with the addition of 2-deoxy-D-glucose, which binds to hexokinase. The blocking of hexokinase prevents the generation of pyruvate, the intermittent substrate required for lactate production even in the presence of glucose. PMID:20566279

Pyrrole-hyaluronic acid conjugates for decreasing cell binding to metals and conducting polymers

PubMed Central

Lee, Jae Young; Schmidt, Christine E.

2010-01-01

Surface modification of electrically conductive biomaterials has been studied to improve biocompatibility for a number of applications, such as implantable sensors and microelectrode arrays. In this study, we electrochemically coated electrodes with biocompatible and non-cell adhesive hyaluronic acid (HA) to reduce cellular adhesion for potential use in neural prostheses. To this end, pyrrole-conjugated hyaluronic acid (PyHA) was synthesized and employed for electrochemical coating of platinum, indium-tin-oxide, and polystyrene sulfonate-doped polypyrrole electrodes. This PyHA conjugate consists of (1) a pyrrole moiety that allows the compound to be electrochemically deposited onto a conductive substrate and (2) non-adhesive HA to minimize cell adhesion and to potentially decrease inflammatory tissue responses. Our characterization results showed the presence of a hydrophilic p(PyHA) layer on the modified electrode, and impedance measurements revealed impedance that was statistically the same as the unmodified electrode. We found that the p(PyHA)-coated electrodes minimized adhesion and migration of fibroblasts and astrocytes for a minimum of up to 3 months. Also, the coating was stable in physiological solution for 3 months and also stable against enzymatic degradation by hyaluronidase. These studies suggest that this p(PyHA)-coating has the potential to be used to mask conducting electrodes from adverse glial responses that occur upon implantation. In addition, electrochemical coating with PyHA can be potentially extended for the surface modification of other metallic and conducting substances such as stents and biosensors. PMID:20558330

Long-Term Stable Adhesion for Conducting Polymers in Biomedical Applications: IrOx and Nanostructured Platinum Solve the Chronic Challenge.

PubMed

Boehler, Christian; Oberueber, Felix; Schlabach, Sabine; Stieglitz, Thomas; Asplund, Maria

2017-01-11

Conducting polymers (CPs) have frequently been described as outstanding coating materials for neural microelectrodes, providing significantly reduced impedance or higher charge injection compared to pure metals. Usability has until now, however, been limited by poor adhesion of polymers like poly(3,4-ethylenedioxythiophene) (PEDOT) to metallic substrates, ultimately precluding long-term applications. The aim of this study was to overcome this weakness of CPs by introducing two novel adhesion improvement strategies that can easily be integrated with standard microelectrode fabrication processes. Iridium Oxide (IrOx) demonstrated exceptional stability for PEDOT coatings, resulting in polymer survival over 10 000 redox cycles and 110 days under accelerated aging conditions at 60 °C. Nanostructured Pt was furthermore introduced as a purely mechanical adhesion promoter providing 10-fold adhesion improvement compared to smooth Pt substrates by simply altering the morphology of Pt. This layer can be realized in a very simple process that is compatible with any electrode design, turning nanostructured Pt into a universal adhesion layer for CP coatings. By the introduction of these adhesion-promoting strategies, the weakness of CP-based neural probes can ultimately be eliminated and true long-term stable use of PEDOT on neural probes will be possible in future electrode generations.

Ruthenium Oxide-Based Microelectrochemical Devices: Electrochemical Behavior of the Oxide Formed by Reduction of RuO4(2-)

DTIC Science & Technology

1988-08-15

the cyclic voltametry when all four electrodes are driven together is larger than for any individual electrode. At very slow scan rates ((10 mV/s...ID vs. VG curve looks more and more like a conventional cyclic voltammogram, exhibiting negative ID on the return sweep . Microelectrode arrays with

In vitro screening of metal oxide nanoparticles for effects on neural function using cortical networks on microelectrode arrays

EPA Science Inventory

Nanoparticles (NPs) may translocate to the brain following inhalation or oral exposures, yet higher throughput methods to screen NPs for potential neurotoxicity are lacking. The present study examined effects of 5 Ce02 (5- 1288 nm), and 4 Ti02 (6-142 nm) NPs and microparticles (M...

GABA-A receptor antagonists increase firing, bursting and synchrony of spontaneous activity in neuronal networks grown on microelectrode arrays: a step towards chemical "fingerprinting"

EPA Science Inventory

Assessment of effects on spontaneous network activity in neurons grown on MEAs is a proposed method to screen chemicals for potential neurotoxicity. In addition, differential effects on network activity (chemical "fingerprints") could be used to classify chemical modes of action....

CHAPTER: In-Situ Characterization of Stimulating Microelectrode Arrays: Study of an Idealized Structure Based on Argus II Retinal implantsBOOK TITLE: Implantable Neural Prostheses 2: Techniques and Engineering Approaches, D.M. Zhou and E. Greenbaum, Eds., Springer, NY 2009

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

Greenbaum, Elias; Sanders, Charlene A; Kandagor, Vincent

The development of a retinal prosthesis for artificial sight includes a study of the factors affecting the structural and functional stability of chronically implanted microelectrode arrays. Although neuron depolarization and propagation of electrical signals have been studied for nearly a century, the use of multielectrode stimulation as a proposed therapy to treat blindness is a frontier area of modern ophthalmology research. Mapping and characterizing the topographic information contained in the electric field potentials and understanding how this information is transmitted and interpreted in the visual cortex is still very much a work in progress. In order to characterize the electricalmore » field patterns generated by the device, an in vitro prototype that mimics several of the physical and chemical parameters of the in vivo visual implant device was fabricated. We carried out multiple electrical measurements in a model 'eye,' beginning with a single electrode, followed by a 9-electrode array structure, both idealized components based on the Argus II retinal implants. Correlating the information contained in the topographic features of the electric fields with psychophysical testing in patients may help reduce the time required for patients to convert the electrical patterns into graphic signals.« less

Simultaneous measurements of ascorbate and glutamate in vivo in the rat brain using carbon fiber nanocomposite sensors and microbiosensor arrays.

PubMed

Ferreira, Nuno R; Ledo, Ana; Laranjinha, João; Gerhardt, Greg A; Barbosa, Rui M

2018-06-01

Nanocomposite sensors consisting of carbon fiber microelectrodes modified with Nafion® and carbon nanotubes, and ceramic-based microelectrode biosensor arrays were used to measure ascorbate and glutamate in the brain with high spatial, temporal and chemical resolution. Nanocomposite sensors displayed electrocatalytic properties towards ascorbate oxidation, translated into a negative shift from +0.20V to -0.05V vs. Ag/AgCl, as well as a significant increase (10-fold) of electroactive surface area. The estimated average basal concentration of ascorbate in vivo in the CA1, CA3 and dentate gyrus (DG) sub regions of the hippocampus were 276±60μM (n=10), 183±30μM (n=10) and 133±42μM (n=10), respectively. The glutamate microbiosensor arrays showed a high sensitivity of 5.3±0.8pAμM -1 (n=18), and LOD of 204±32nM (n=10), and t 50% response time of 0.9±0.02s (n=6) and high selectivity against major interferents. The simultaneous and real-time measurements of glutamate and ascorbate in the hippocampus of anesthetized rats following local stimulus with KCl or glutamate revealed a dynamic interaction between the two neurochemicals. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Reusable conductimetric array of interdigitated microelectrodes for the readout of low-density microarrays.

PubMed

Mallén, Maria; Díaz-González, María; Bonilla, Diana; Salvador, Juan P; Marco, María P; Baldi, Antoni; Fernández-Sánchez, César

2014-06-17

Low-density protein microarrays are emerging tools in diagnostics whose deployment could be primarily limited by the cost of fluorescence detection schemes. This paper describes an electrical readout system of microarrays comprising an array of gold interdigitated microelectrodes and an array of polydimethylsiloxane microwells, which enabled multiplexed detection of up to thirty six biological events on the same substrate. Similarly to fluorescent readout counterparts, the microarray can be developed on disposable glass slide substrates. However, unlike them, the presented approach is compact and requires a simple and inexpensive instrumentation. The system makes use of urease labeled affinity reagents for developing the microarrays and is based on detection of conductivity changes taking place when ionic species are generated in solution due to the catalytic hydrolysis of urea. The use of a polydimethylsiloxane microwell array facilitates the positioning of the measurement solution on every spot of the microarray. Also, it ensures the liquid tightness and isolation from the surrounding ones during the microarray readout process, thereby avoiding evaporation and chemical cross-talk effects that were shown to affect the sensitivity and reliability of the system. The performance of the system is demonstrated by carrying out the readout of a microarray for boldenone anabolic androgenic steroid hormone. Analytical results are comparable to those obtained by fluorescent scanner detection approaches. The estimated detection limit is 4.0 ng mL(-1), this being below the threshold value set by the World Anti-Doping Agency and the European Community. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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 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.

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

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.

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.

Rapid microelectrode measurements and the origin and regulation of extracellular glutamate in rat prefrontal cortex.

PubMed

Hascup, Erin R; Hascup, Kevin N; Stephens, Michelle; Pomerleau, Francois; Huettl, Peter; Gratton, Alain; Gerhardt, Greg A

2010-12-01

Glutamate in the prefrontal cortex (PFC) plays a significant role in several mental illnesses, including schizophrenia, addiction and anxiety. Previous studies on PFC glutamate-mediated function have used techniques that raise questions on the neuronal versus astrocytic origin of glutamate. The present studies used enzyme-based microelectrode arrays to monitor second-by-second resting glutamate levels in the PFC of awake rats. Locally applied drugs were employed in an attempt to discriminate between the neuronal or glial components of the resting glutamate signal. Local application of tetrodotoxin (sodium channel blocker), produced a significant (∼ 40%) decline in resting glutamate levels. In addition significant reductions in extracellular glutamate were seen with locally applied ω-conotoxin (MVIIC; ∼ 50%; calcium channel blocker), and the mGluR(2/3) agonist, LY379268 (∼ 20%), and a significant increase with the mGluR(2/3) antagonist LY341495 (∼ 40%), effects all consistent with a large neuronal contribution to the resting glutamate levels. Local administration of D,L-threo-β-benzyloxyaspartate (glutamate transporter inhibitor) produced an ∼ 120% increase in extracellular glutamate levels, supporting that excitatory amino acid transporters, which are largely located on glia, modulate clearance of extracellular glutamate. Interestingly, local application of (S)-4-carboxyphenylglycine (cystine/glutamate antiporter inhibitor), produced small, non-significant bi-phasic changes in extracellular glutamate versus vehicle control. Finally, pre-administration of tetrodotoxin completely blocked the glutamate response to tail pinch stress. Taken together, these results support that PFC resting glutamate levels in rats as measured by the microelectrode array technology are at least 40-50% derived from neurons. Furthermore, these data support that the impulse flow-dependent glutamate release from a physiologically -evoked event is entirely neuronally derived. © 2010 The Authors. Journal of Neurochemistry © 2010 International Society for Neurochemistry.

Catalytically induced electrokinetics for motors and micropumps.

PubMed

Paxton, Walter F; Baker, Paul T; Kline, Timothy R; Wang, Yang; Mallouk, Thomas E; Sen, Ayusman

2006-11-22

We have explored the role of electrokinetics in the spontaneous motion of platinum-gold nanorods suspended in hydrogen peroxide (H2O2) solutions that may arise from the bimetallic electrochemical decomposition of H2O2. The electrochemical decomposition pathway was confirmed by measuring the steady-state short-circuit current between platinum and gold interdigitated microelectrodes (IMEs) in the presence of H2O2. The resulting ion flux from platinum to gold implies an electric field in the surrounding solution that can be estimated from Ohm's Law. This catalytically generated electric field could in principle bring about electrokinetic effects that scale with the Helmholtz-Smoluchowski equation. Accordingly, we observed a linear relationship between bimetallic rod speed and the resistivity of the bulk solution. Previous observations relating a decrease in speed to an increase in ethanol concentration can be explained in terms of a decrease in current density caused by the presence of ethanol. Furthermore, we found that the catalytically generated electric field in the solution near a Pt/Au IME in the presence of H2O2 is capable of inducing electroosmotic fluid flow that can be switched on and off externally. We demonstrate that the velocity of the fluid flow in the plane of the IME is a function of the electric field, whether catalytically generated or applied from an external current source. Our findings indicate that the motion of PtAu nanorods in H2O2 is primarily due to a catalytically induced electrokinetic phenomenon and that other mechanisms, such as those related to interfacial tension gradients, play at best a minor role.

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.

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.

Photoresponsive peptide azobenzene conjugates that specifically interact with platinum surfaces

NASA Astrophysics Data System (ADS)

Dinçer, S.; Tamerler, C.; Sarıkaya, M.; Pişkin, E.

2008-05-01

The aim of this study is to prepare photoresponsive peptide-azobenzene compounds which interacts with platinum surfaces specifically, in order to create smart surfaces for further novel applications in design of smart biosensors and array platforms. Here, a water-soluble azobenzene molecule, 4-hydroxyazo benzene,4-sulfonic acid was synthesized by diazo coupling reaction. A platinum-specific peptide, originally selected by a phage display technique was chemically synthesized/purchased, and conjugated with the azobenzene compound activated with carbonyldiimidazole. Both azobenzene and its conjugate were characterized (including photoresponsive properties) by FTIR, NMR, and UV-spectrophotometer. The yield of conjugation reaction estimated by ninhydrin assay was about 65%. Peptide incorporation did not restrict the light-sensitivity of azobenzene. Adsorption of both the peptide and its azobenzene conjugate was followed by Quartz Crystal Microbalance (QCM) system. The kinetic evaluations exhibited that both molecules interact platinum surfaces, quite rapidly and strongly.

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.

A novel 384-multiwell microelectrode array for the impedimetric monitoring of Tau protein induced neurodegenerative processes.

PubMed

Jahnke, Heinz-Georg; Krinke, Dana; Seidel, Diana; Lilienthal, Katharina; Schmidt, Sabine; Azendorf, Ronny; Fischer, Michael; Mack, Till; Striggow, Frank; Althaus, Holger; Schober, Andreas; Robitzki, Andrea A

2017-02-15

Over the last decades, countless bioelectronic monitoring systems were developed for the analysis of cells as well as complex tissues. Most studies addressed the sensitivity and specificity of the bioelectronic detection method in comparison to classical molecular biological assays. In contrast, the up scaling as a prerequisite for the practical application of these novel bioelectronic monitoring systems is mostly only discussed theoretically. In this context, we developed a novel 384-multiwell microelectrode array (MMEA) based measurement system for the sensitive label-free real-time monitoring of neurodegenerative processes by impedance spectroscopy. With respect to the needs of productive screening systems for robust and reproducible measurements on high numbers of plates, we focused on reducing the critical contacting of more than 400 electrodes for a 384-MMEA. Therefore, we introduced an on top array of immersive counter electrodes that are individually addressed by a multiplexer and connected all measurement electrodes on the 384-MMEA to a single contact point. More strikingly, our novel approach provided a comparable signal stability and sensitivity similar to an array with integrated counter electrodes. Next, we optimized a SH-SY5Y cell based tauopathy model by introducing a novel 5-fold Tau mutation eliminating the need of artificial tauopathy induction. In combination with our novel 384-MMEA based measurement system, the concentration and time dependent neuroregenerative effect of the kinase inhibitor SRN-003-556 could be quantitatively monitored. Thus, our novel screening system could be a useful tool to identify and develop potential novel therapeutics in the field of Tau-related neurodegenerative diseases. Copyright © 2016. Published by Elsevier B.V.

Performance of conducting polymer electrodes for stimulating neuroprosthetics

NASA Astrophysics Data System (ADS)

Green, R. A.; Matteucci, P. B.; Hassarati, R. T.; Giraud, B.; Dodds, C. W. D.; Chen, S.; Byrnes-Preston, P. J.; Suaning, G. J.; Poole-Warren, L. A.; Lovell, N. H.

2013-02-01

Objective. Recent interest in the use of conducting polymers (CPs) for neural stimulation electrodes has been growing; however, concerns remain regarding the stability of coatings under stimulation conditions. These studies examine the factors of the CP and implant environment that affect coating stability. The CP poly(ethylene dioxythiophene) (PEDOT) is examined in comparison to platinum (Pt), to demonstrate the potential performance of these coatings in neuroprosthetic applications. Approach. PEDOT is coated on Pt microelectrode arrays and assessed in vitro for charge injection limit and long-term stability under stimulation in biologically relevant electrolytes. Physical and electrical stability of coatings following ethylene oxide (ETO) sterilization is established and efficacy of PEDOT as a visual prosthesis bioelectrode is assessed in the feline model. Main results. It was demonstrated that PEDOT reduced the potential excursion at a Pt electrode interface by 72% in biologically relevant solutions. The charge injection limit of PEDOT for material stability was found to be on average 30× larger than Pt when tested in physiological saline and 20× larger than Pt when tested in protein supplemented media. Additionally stability of the coating was confirmed electrically and morphologically following ETO processing. It was demonstrated that PEDOT-coated electrodes had lower potential excursions in vivo and electrically evoked potentials (EEPs) could be detected within the visual cortex. Significance. These studies demonstrate that PEDOT can be produced as a stable electrode coating which can be sterilized and perform effectively and safely in neuroprosthetic applications. Furthermore these findings address the necessity for characterizing in vitro properties of electrodes in biologically relevant milieu which mimic the in vivo environment more closely.

Electronic Skin with Multifunction Sensors Based on Thermosensation.

PubMed

Zhao, Shuai; Zhu, Rong

2017-04-01

A multifunctional electronic skin (e-skin) with multimodal sensing capabilities of perceiving mechanical and thermal stimuli, discriminating matter type, and sensing wind is developed using the thermosensation of a platinum ribbon array, whose temperature varies with conductive or convective heat transfer toward the surroundings. Pressure is perceived by a porous elastomer covering on the heated platinum ribbon, which bears mechanical-thermal conversion to allow high integration with other sensors. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\mbi{\\mu }}$\\end{document}-Foil Polymer Electrode Array for Intracortical Neural Recordings

PubMed Central

Köhler, Per; Granmo, Marcus; Schouenborg, Jens; Bengtsson, Martin; Wallman, Lars

2014-01-01

We have developed a multichannel electrode array—termed \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}\\(\\mu \\) \\end{document}-foil—that comprises ultrathin and flexible electrodes protruding from a thin foil at fixed distances. In addition to allowing some of the active sites to reach less compromised tissue, the barb-like protrusions that also serves the purpose of anchoring the electrode array into the tissue. This paper is an early evaluation of technical aspects and performance of this electrode array in acute in vitro/in vivo experiments. The interface impedance was reduced by up to two decades by electroplating the active sites with platinum black. The platinum black also allowed for a reduced phase lag for higher frequency components. The distance between the protrusions of the electrode array was tailored to match the architecture of the rat cerebral cortex. In vivo acute measurements confirmed a high signal-to-noise ratio for the neural recordings, and no significant crosstalk between recording channels. PMID:27170864

Tungsten trioxide nanoplate array supported platinum as a highly efficient counter electrode for dye-sensitized solar cells.

PubMed

Song, Dandan; Cui, Peng; Zhao, Xing; Li, Meicheng; Chu, Lihua; Wang, Tianyue; Jiang, Bing

2015-03-19

A tungsten trioxide (WO₃) nanoplate array is fabricated directly on the FTO/glass substrate and used as a platinum (Pt) nanoscale supporter for a highly efficient and low Pt-consumption counter electrode (CE) in dye-sensitized solar cells (DSCs). A Pt/WO₃ composite structure, with Pt nanoparticles having a diameter of 2-3 nm, increases the electrochemical catalytic activity in catalyzing the reduction of triiodide. Accordingly, the power conversion efficiency is increased from less than 1% for WO₃ CE and 8.1% for Pt CE, respectively, to 8.9% for Pt/WO₃ CE. Moreover, the use of Pt/WO₃ CE can dramatically reduce the consumption of scarce Pt material, with a relatively low Pt-loading of ∼2 μg cm(-2), while maintaining a much better performance. The excellent performance of Pt/WO₃ CE is attributed to the efficient electron injection and transport via WO₃ supporters, as well as the nanostructure array morphology of WO₃ for deposition of fine Pt nanoparticles. This work provides an approach for developing highly catalytic and low-cost Pt based CEs, which also has implications for the development of Pt/WO₃ nanoplate arrays for other applications.

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

Controlled Trapping of Onion-Like Carbon (OLC) via Dielectrophoresis

NASA Astrophysics Data System (ADS)

Olariu, Marius; Arcire, Alexandru; Plonska-Brzezinska, Marta E.

2017-01-01

Manipulation of onion-like carbon (OLC), also known as carbon nano-onions (CNOs), at the level of various arrays of microelectrodes is vital in practical applications such as biological and chemical sensing, ultracapacitors (supercapacitors), electromagnetic shielding, catalysis, tribology, optical limiting and molecular junctions in scanning tunneling microscopy, and field-effect transistors. In spite of technological developments in this area, rigorous handling of carbon nano-onions towards desired locations within a device remains a challenge, and the quantity of OLC required significantly influences the price of the final electrical or electronic device. We present herein an experimental study on electromanipulation and trapping of onion-like carbon (OLC) at the level of gold-patterned interdigitated microelectrodes through dielectrophoresis. The influence of the magnitude as well as frequency of the alternating-current (AC) voltage employed for OLC trapping is discussed in detail. The effects of tuning the AC field strength and frequency on the OLC trapping behavior are also considered.

An integrated micro-manipulation and biosensing platform built in glass-based LTPS TFT technology

NASA Astrophysics Data System (ADS)

Chen, Lei-Guang; Wu, Dong-Yi; S-C Lu, Michael

2012-09-01

The glass-based low-temperature polycrystalline-silicon (LTPS) thin-film transistor (TFT) process, widely known for making liquid crystal displays, is utilized in this work to realize a fully integrated, microbead-based micro-manipulation and biosensing platform. The operation utilizes arrays of microelectrodes made of transparent iridium tin oxide (ITO) to move the immobilized polystyrene microbeads to the sensor surface by dielectrophoresis (DEP). Detection of remaining microbeads after a specific antigen/antibody reaction is accomplished by photo-detectors under the transparent electrodes. It was found that microbeads can be driven successfully by the 30 × 30 µm2 microelectrodes separated by 10 µm with no more than 6 Vp-p, which is compatible with the operating range of thin-film transistors. Microbeads immobilized with antimouse immunoglobulin (IgG) and prostate-specific antigen (PSA) antibody were successfully detected after specific binding, illustrating the potential of LTPS TFT microarrays for more versatile biosensing applications.

DcR3 binds to ovarian cancer via heparan sulfate proteoglycans and modulates tumor cells response to platinum with corresponding alteration in the expression of BRCA1

PubMed Central

2012-01-01

Background Overcoming platinum resistance is a major obstacle in the treatment of Epithelial Ovarian Cancer (EOC). In our previous work Decoy Receptor 3 (DcR3) was found to be related to platinum resistance. The major objective of this work was to define the cellular interaction of DcR3 with EOC and to explore its effects on platinum responsiveness. Methods We studied cell lines and primary cultures for the expression of and the cells ability to bind DcR3. Cells were cultured with DcR3 and then exposed to platinum. Cell viability was determined by MTT assay. Finally, the cells molecular response to DcR3 was studied using real time RT-PCR based differential expression arrays, standard RT-PCR, and Western blot. Results High DcR3 in the peritoneal cavity of women with EOC is associated with significantly shorter time to first recurrence after platinum based therapy (p = 0.02). None-malignant cells contribute DcR3 in the peritoneal cavity. The cell lines studied do not secrete DcR3; however they all bind exogenous DcR3 to their surface implying that they can be effected by DcR3 from other sources. DcR3s protein binding partners are minimally expressed or negative, however, all cells expressed the DcR3 binding Heparan Sulfate Proteoglycans (HSPGs) Syndecans-2, and CD44v3. DcR3 binding was inhibited by heparin and heparinase. After DcR3 exposure both SKOV-3 and OVCAR-3 became more resistant to platinum with 15% more cells surviving at high doses. On the contrary CaOV3 became more sensitive to platinum with 20–25% more cell death. PCR array analysis showed increase expression of BRCA1 mRNA in SKOV-3 and OVCAR-3 and decreased BRCA1 expression in CaOV-3 after exposure to DcR3. This was confirmed by gene specific real time PCR and Western blot analysis. Conclusions Non-malignant cells contribute to the high levels of DcR3 in ovarian cancer. DcR3 binds readily to EOC cells via HSPGs and alter their responsiveness to platinum chemotherapy. The paradoxical responses seen were related to the expression pattern of HSPGs available on the cells surface to interact with. Although the mechanism behind this is not completely known alterations in DNA repair pathways including the expression of BRCA1 appear to be involved. PMID:22583667

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

DTIC Science & Technology

2015-10-01

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

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

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 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.

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.

Investigating brain functional evolution and plasticity using microelectrode array technology.

PubMed

Napoli, Alessandro; Obeid, Iyad

2015-10-01

The aim of this work was to investigate long and short-term plasticity responsible for memory formation in dissociated neuronal networks. In order to address this issue, a set of experiments was designed and implemented in which the microelectrode array electrode grid was divided into four quadrants, two of which were chronically stimulated, every two days for one hour with a stimulation paradigm that varied over time. Overall network and quadrant responses were then analyzed to quantify what level of plasticity took place in the network and how this was due to the stimulation interruption. The results demonstrate that there were no spatial differences in the stimulus-evoked activity within quadrants. Furthermore, the implemented stimulation protocol induced depression effects in the neuronal networks as demonstrated by the consistently lower network activity following stimulation sessions. Finally, the analysis demonstrated that the inhibitory effects of the stimulation decreased over time, thus suggesting a habituation phenomenon. These findings are sufficient to conclude that electrical stimulation is an important tool to interact with dissociated neuronal cultures, but localized stimuli are not enough to drive spatial synaptic potentiation or depression. On the contrary, the ability to modulate synaptic temporal plasticity was a feasible task to achieve by chronic network stimulation. Copyright © 2015 Elsevier Inc. All rights reserved.

Establishment of a Long-Term Chick Forebrain Neuronal Culture on a Microelectrode Array Platform

PubMed Central

Kuang, Serena Y.; Huang, Ting; Wang, Zhonghai; Lin, Yongliang; Kindy, Mark; Xi, Tingfei; Gao, Bruce Z.

2016-01-01

The biosensor system formed by culturing primary animal neurons on a microelectrode array (MEA) platform is drawing an increasing research interest for its power as a rapid, sensitive, functional neurotoxicity assessment, as well as for many other electrophysiological related research purposes. In this paper, we established a long-term chick forebrain neuron culture (C-FBN-C) on MEAs with a more than 5 month long lifespan and up to 5 month long stability in morphology and physiological function; characterized the C-FBN-C morphologically, functionally, and developmentally; partially compared its functional features with rodent counterpart; and discussed its pros and cons as a novel biosensor system in comparison to rodent counterpart and human induced pluripotent stem cells (hiPSCs). Our results show that C-FBN-C on MEA platform 1) can be used as a biosensor of its own type in a wide spectrum of basic biomedical research; 2) is of value in comparative physiology in cross-species studies; and 3) may have potential to be used as an alternative, cost-effective approach to rodent counterpart within shared common functional domains (such as specific types of ligand-gated ion channel receptors and subtypes expressed in the cortical tissues of both species) in large-scale environmental neurotoxicant screening that would otherwise require millions of animals. PMID:26989485

Microelectrode array-induced neuronal alignment directs neurite outgrowth: analysis using a fast Fourier transform (FFT).

PubMed

Radotić, Viktorija; Braeken, Dries; Kovačić, Damir

2017-12-01

Many studies have shown that the topography of the substrate on which neurons are cultured can promote neuronal adhesion and guide neurite outgrowth in the same direction as the underlying topography. To investigate this effect, isotropic substrate-complementary metal-oxide-semiconductor (CMOS) chips were used as one example of microelectrode arrays (MEAs) for directing neurite growth of spiral ganglion neurons. Neurons were isolated from 5 to 7-day-old rat pups, cultured 1 day in vitro (DIV) and 4 DIV, and then fixed with 4% paraformaldehyde. For analysis of neurite alignment and orientation, fast Fourier transformation (FFT) was used. Results revealed that on the micro-patterned surface of a CMOS chip, neurons orient their neurites along three directional axes at 30, 90, and 150° and that neurites aligned in straight lines between adjacent pillars and mostly followed a single direction while occasionally branching perpendicularly. We conclude that the CMOS substrate guides neurites towards electrodes by means of their structured pillar organization and can produce electrical stimulation of aligned neurons as well as monitoring their neural activities once neurites are in the vicinity of electrodes. These findings are of particular interest for neural tissue engineering with the ultimate goal of developing a new generation of MEA essential for improved electrical stimulation of auditory neurons.

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.

Fringing-field dielectrophoretic assembly of ultrahigh-density semiconducting nanotube arrays with a self-limited pitch

NASA Astrophysics Data System (ADS)

Cao, Qing; Han, Shu-Jen; Tulevski, George S.

2014-09-01

One key challenge of realizing practical high-performance electronic devices based on single-walled carbon nanotubes is to produce electronically pure nanotube arrays with both a minuscule and uniform inter-tube pitch for sufficient device-packing density and homogeneity. Here we develop a method in which the alternating voltage-fringing electric field formed between surface microelectrodes and the substrate is utilized to assemble semiconducting nanotubes into well-aligned, ultrahigh-density and submonolayered arrays, with a consistent pitch as small as 21±6 nm determined by a self-limiting mechanism, based on the unique field focusing and screening effects of the fringing field. Field-effect transistors based on such nanotube arrays exhibit record high device transconductance (>50 μS μm-1) and decent on current per nanotube (~1 μA per tube) together with high on/off ratios at a drain bias of -1 V.

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.

Electro-Immobilization of Acetylcholinesterase Using Polydopamine for Carbaryl Microsensor

NASA Astrophysics Data System (ADS)

Ha, Trung B.; Le, Huyen T.; Cao, Ha H.; Binh, Nguyen Thanh; Nguyen, Huy L.; Dang, Le Hai; Do, Quan P.; Nguyen, Dzung T.; Lam, Tran Dai; Nguyen, Vân-Anh

2018-02-01

A simple and sensitive electrochemical acetylcholinesterase (AChE) biosensor for determination of carbaryl, one of the most commonly used carbamate pesticides, is described. The AChE enzyme was successfully entrapped by a polydopamine-graphene composite on polypyrrole nanowires that modified interdigitated planar platinum-film microelectrodes . The influence of different parameters on the operation of the biosensor was also studied. The selected parameters for the biosensor performance in detecting carbaryl were as follows: applied potential + 0.7 V, pH 7.4 at 25°C. The inhibition of carbaryl was proportional to its concentrations ranging from 0.05 to 1.5 μg/mL with the detection limit of 0.008 μg/mL using chronoamperometry. This study provides a promising approach in fabrication of sensitive biosensors for the analysis of carbamate pesticides as well as other hazardous compounds.

Photoelectrochemical CdSe/TiO2 nanotube array microsensor for high-resolution in-situ detection of dopamine.

PubMed

Qin, Caidie; Bai, Xue; Zhang, Yue; Gao, Kai

2018-05-03

A photoelectrochemical wire microelectrode was constructed based on the use of a TiO 2 nanotube array with electrochemically deposited CdSe semiconductor. A strongly amplified photocurrent is generated on the sensor surface. The microsensor has a response in the 0.05-20 μM dopamine (DA) concentration range and a 16.7 μM detection limit at a signal-to-noise ratio of 3. Sensitivity, recovery and reproducibility of the sensor were validated by detecting DA in spiked human urine, and satisfactory results were obtained. Graphical abstract Schematic of a sensitive photoelectrochemical microsensor based on CdSe modified TiO 2 nanotube array. The photoelectrochemical microsensor was successfully applied to the determination of dopamine in urine samples.

1997 Report to the Congress on Ballistic Missile Defense.

DTIC Science & Technology

1997-10-01

Infrared Arrays • Quantum Well Infrared Photodector (QWIP) Focal Plane Array (FPA) • Staring Si Impurity Band Conduction Extremely Sensitive Focal...to be flown on STRV lc/d include a Quantum Well Infrared Photometer (QWIP) sensor and a multifunctional compos- ite structure. The Space Technology...Peoples Republic of China Platinum Silicide Quick Reaction Program Quick Response Program Quantum Well Infrared Photometer Research and

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.

Ultrasensitive electrochemical immunosensors for multiplexed determination using mesoporous platinum nanoparticles as nonenzymatic labels.

PubMed

Cui, Zhentao; Wu, Dan; Zhang, Yong; Ma, Hongmin; Li, He; Du, Bin; Wei, Qin; Ju, Huangxian

2014-01-07

An ultrasensitive multiplexed immunoassay method was developed at a disposable immunosensor array using mesoporous platinum nanoparticles (M-Pt NPs) as nonenzymatic labels. M-Pt NPs were prepared by ultrasonic method and employed to label the secondary antibody (Ab2) for signal amplification. The immunosensor array was constructed by covalently immobilizing capture antibody (Ab1) on graphene modified screen printed carbon electrodes (SPECs). After the sandwich-type immunoreactions, the M-Pt-Ab2 was bound to immunosensor surface to catalyze the electro-reduction of H2O2 reaction, which produced detectable signals for readout of analytes. Using breast cancer related panel of tumor markers (CA125, CA153 and CEA) as model analytes, this method showed wide linear ranges of over 4 orders of magnitude with the detection limits of 0.002 U mL(-1), 0.001 U mL(-1) and 7.0 pg mL(-1) for CA125, CA153 and CEA, respectively. The disposable immunosensor array possessed excellent clinical value in cancer screening as well as convenient point of care diagnostics. Copyright © 2013 Elsevier B.V. All rights reserved.

In vitro biocompatibility and electrical stability of thick-film platinum/gold alloy electrodes printed on alumina

NASA Astrophysics Data System (ADS)

Carnicer-Lombarte, Alejandro; Lancashire, Henry T.; Vanhoestenberghe, Anne

2017-06-01

Objective. High-density electrode arrays are a powerful tool in both clinical neuroscience and basic research. However, current manufacturing techniques require the use of specialised techniques and equipment, which are available to few labs. We have developed a high-density electrode array with customisable design, manufactured using simple printing techniques and with commercially available materials. Approach. Electrode arrays were manufactured by thick-film printing a platinum-gold alloy (Pt/Au) and an insulating dielectric on 96% alumina ceramic plates. Arrays were conditioned in serum and serum-free conditions, with and without 1 kHz, 200 µA, charge balanced stimulation for up to 21 d. Array biocompatibility was assessed using an extract assay and a PC-12 cell contact assay. Electrode impedance, charge storage capacity and charge injection capacity were before and after array conditioning. Main results. The manufactured Pt/Au electrodes have a highly porous surface and exhibit electrical properties comparable to arrays manufactured using alternative techniques. Materials used in array manufacture were found to be non-toxic to L929 fibroblasts by extract assay, and neuronal-like PC-12 cells adhered and extended neurites on the array surfaces. Arrays remained functional after long-term delivery of electrical pulses while exposed to protein-rich environments. Charge storage capacities and charge injection capacities increased following stimulation accounted for by an increase in surface index (real surface area) observed by vertical scanning interferometry. Further, we observed accumulation of proteins at the electrode sites following conditioning in the presence of serum. Significance. This study demonstrates the in vitro biocompatibility of commercially available thick-film printing materials. The printing technique is both simple and versatile, with layouts readily modified to produce customized electrode arrays. Thick-film electrode arrays are an attractive tool that may be implemented for general tissue engineering and neuroscience research.

A sensitive impedance biosensor based on immunomagnetic separation and urease catalysis for rapid detection of Listeria monocytogenes using an immobilization-free interdigitated array microelectrode.

PubMed

Chen, Qi; Lin, Jianhan; Gan, Chengqi; Wang, Yuhe; Wang, Dan; Xiong, Yonghua; Lai, Weihua; Li, Yuntao; Wang, Maohua

2015-12-15

In this study, we described a novel impedance biosensor combining immunomagnetic separation with urease catalysis for sensitive detection of foodborne bacteria using Listeria monocytogenes as model and an immobilization-free microelectrode as detector. The monoclonal antibodies (MAbs) were immobilized on the surface of the magnetic nanoparticles (MNPs) with the diameter of 180 nm by biotin-streptavidin system for specifically and efficiently separating Listeria cells from sample background. The polyclonal antibodies (PAbs) and the urease were modified onto the surface of the gold nanoparticles (AuNPs) with the diameter of 20 nm and the modified AuNPs were used to react with Listera to form the MNP-MAb-Listeria-PAb-AuNP-urease sandwich complexes. The urease in the complexes could catalyze the hydrolysis of the urea into ammonium carbonate and this led to an increase in the ionic strength of the media, which could be detected by the microelectrode. The magnetic separation efficiencies for L. monocytogenes at the concentrations ranging from 3.0×10(1) to 3.0×10(4) CFU/mL were over 95% for the pure cultures and over 85% for the spiked lettuce samples. The lower detection limit of this biosensor for L. monocytogenes was found to be 300 CFU/mL in both the pure cultures and the spiked lettuce samples. The microelectrode was demonstrated to be reusable for over 50 times with thorough cleaning by deionized water. This biosensor showed its potential to provide a simple, low-cost and sensitive method for rapid screening of foodborne pathogens and could be extended for detection of other biological or chemical targets. Copyright © 2015 Elsevier B.V. All rights reserved.

Electrochemical and in vitro neuronal recording characteristics of multi-electrode arrays surface-modified with electro-co-deposited gold-platinum nanoparticles.

PubMed

Kim, Yong Hee; Kim, Ah Young; Kim, Gook Hwa; Han, Young Hwan; Chung, Myung-Ae; Jung, Sang-Don

2016-02-01

In order to complement the high impedance electrical property of gold nanoparticles (Au NPs) we have performed electro-co-deposition of gold-platinum nanoparticles (Au-Pt NPs) onto the Au multi-electrode array (MEA) and modified the Au-Pt NPs surface with cell adhesive poly-D-lysine via thiol chemistry based covalent binding. The Au-Pt NPs were analyzed to have bimetallic nature not the mixture of Au NPs and Pt NPs by X-ray diffraction analysis and to have impedance value (4.0 × 10(4) Ω (at 1 kHz)) comparable to that of Pt NPs. The performance of Au-Pt NP-modified MEAs was also checked in relation to neuronal signal recording. The noise level in Au-Pt NP-modified MEAs was lower than in that of Au NP-modified MEA.

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.

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

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.

Automated electric valve for electrokinetic separation in a networked microfluidic chip.

PubMed

Cui, Huanchun; Huang, Zheng; Dutta, Prashanta; Ivory, Cornelius F

2007-02-15

This paper describes an automated electric valve system designed to reduce dispersion and sample loss into a side channel when an electrokinetically mobilized concentration zone passes a T-junction in a networked microfluidic chip. One way to reduce dispersion is to control current streamlines since charged species are driven along them in the absence of electroosmotic flow. Computer simulations demonstrate that dispersion and sample loss can be reduced by applying a constant additional electric field in the side channel to straighten current streamlines in linear electrokinetic flow (zone electrophoresis). This additional electric field was provided by a pair of platinum microelectrodes integrated into the chip in the vicinity of the T-junction. Both simulations and experiments of this electric valve with constant valve voltages were shown to provide unsatisfactory valve performance during nonlinear electrophoresis (isotachophoresis). On the basis of these results, however, an automated electric valve system was developed with improved valve performance. Experiments conducted with this system showed decreased dispersion and increased reproducibility as protein zones isotachophoretically passed the T-junction. Simulations of the automated electric valve offer further support that the desired shape of current streamlines was maintained at the T-junction during isotachophoresis. Valve performance was evaluated at different valve currents based on statistical variance due to dispersion. With the automated control system, two integrated microelectrodes provide an effective way to manipulate current streamlines, thus acting as an electric valve for charged species in electrokinetic separations.

Micromachined electrode array

DOEpatents

Okandan, Murat; Wessendorf, Kurt O.

2007-12-11

An electrode array is disclosed which has applications for neural stimulation and sensing. The electrode array, in certain embodiments, can include a plurality of electrodes each of which is flexibly attached to a common substrate using a plurality of springs to allow the electrodes to move independently. In other embodiments of the electrode array, the electrodes can be fixed to the substrate. The electrode array can be formed from a combination of bulk and surface micromachining, and can include electrode tips having an electroplated metal (e.g. platinum, iridium, gold or titanium) or a metal oxide (e.g. iridium oxide) for biocompatibility. The electrode array can be used to form a part of a neural prosthesis, and is particularly well adapted for use in an implantable retinal prosthesis.

Pillar cuvettes: capillary-filled, microliter quartz cuvettes with microscale path lengths for optical spectroscopy.

PubMed

Holzner, Gregor; Kriel, Frederik Hermanus; Priest, Craig

2015-05-05

The goal of most analytical techniques is to reduce the lower limit of detection; however, it is sometimes necessary to do the opposite. High sample concentrations or samples with high molar absorptivity (e.g., dyes and metal complexes) often require multiple dilution steps or laborious sample preparation prior to spectroscopic analysis. Here, we demonstrate dilution-free, one-step UV-vis spectroscopic analysis of high concentrations of platinum(IV) hexachloride in a micropillar array, that is, "pillar cuvette". The cuvette is spontaneously filled by wicking of the liquid sample into the micropillar array. The pillar height (thus, the film thickness) defines the optical path length, which was reduced to between 10 and 20 μm in this study (3 orders of magnitude smaller than in a typical cuvette). Only one small droplet (∼2 μL) of sample is required, and the dispensed volume need not be precise or even known to the analyst for accurate spectroscopy measurements. For opaque pillars, we show that absorbance is linearly related to platinum concentration (the Beer-Lambert Law). For fully transparent or semitransparent pillars, the measured absorbance was successfully corrected for the fractional surface coverage of the pillars and the transmittance of the pillars and reference. Thus, both opaque and transparent pillars can be applied to absorbance spectroscopy of high absorptivity, microliter samples. It is also shown here that the pillar array has a useful secondary function as an integrated (in-cuvette) filter for particulates. For pillar cuvette measurements of platinum solutions spiked with 6 μm diameter polystyrene spheres, filtered and unfiltered samples gave identical spectra.

Design, fabrication, and evaluation of on-chip micro-supercapacitors

NASA Astrophysics Data System (ADS)

Beidaghi, Majid

Due to the increasing demand for high power and reliable miniaturized energy storage devices, the development of micro-supercapacitors or electrochemical micro-capacitors have attracted much attention in recent years. This dissertation investigates several strategies to develop on-chip micro-supercapacitors with high power and energy density. Micro-supercapacitors based on interdigitated carbon micro-electrode arrays are fabricated through carbon microelectromechanical systems (C-MEMS) technique which is based on carbonization of patterned photoresist. To improve the capacitive behavior, electrochemical activation is performed on carbon micro-electrode arrays. The developed micro-supercapacitors show specific capacitances as high as 75 mFcm-2 at a scan rate of 5 mVs -1 after electrochemical activation for 30 minutes. The capacitance loss is less than 13% after 1000 cyclic voltammetry (CV) cycles. These results indicate that electrochemically activated C-MEMS micro-electrode arrays are promising candidates for on-chip electrochemical micro-capacitor applications. The energy density of micro-supercapacitors was further improved by conformal coating of polypyrrole (PPy) on C-MEMS structures. In these types of micro-devices the three dimensional (3D) carbon microstructures serve as current collectors for high energy density PPy electrodes. The electrochemical characterizations of these micro-supercapacitors show that they can deliver a specific capacitance of about 162.07 mFcm-2 and a specific power of 1.62mWcm -2 at a 20 mVs-1 scan rate. Addressing the need for high power micro-supercapacitors, the application of graphene as electrode materials for micro-supercapacitor was also investigated. The present study suggests a novel method to fabricate graphene-based micro-supercapacitors with thin film or in-plane interdigital electrodes. The fabricated micro-supercapacitors show exceptional frequency response and power handling performance and could effectively charge and discharge at rates as high as 50 Vs-1. CV measurements show that the specific capacitance of the micro-supercapacitor based on reduced graphene oxide and carbon nanotube composites is 6.1 mFcm -2 at scan rate of 0.01Vs-1. At a very high scan rate of 50 Vs-1, a specific capacitance of 2.8 mFcm-2 (stack capacitance of 3.1 Fcm-3) is recorded. This unprecedented performance can potentially broaden the future applications of micro-supercapacitors.

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.

Proton exchange membrane fuel cells for space and electric vehicle applications: From basic research to technology development

NASA Technical Reports Server (NTRS)

Srinivasan, Supramaniam; Mukerjee, Sanjeev; Parthasarathy, A.; CesarFerreira, A.; Wakizoe, Masanobu; Rho, Yong Woo; Kim, Junbom; Mosdale, Renaut A.; Paetzold, Ronald F.; Lee, James

1994-01-01

The proton exchange membrane fuel cell (PEMFC) is one of the most promising electrochemical power sources for space and electric vehicle applications. The wide spectrum of R&D activities on PEMFC's, carried out in our Center from 1988 to date, is as follows (1) Electrode Kinetic and Electrocatalysis of Oxygen Reduction; (2) Optimization of Structures of Electrodes and of Membrane and Electrode Assemblies; (3) Selection and Evaluation of Advanced Proton Conducting Membranes and of Operating Conditions to Attain High Energy Efficiency; (4) Modeling Analysis of Fuel Cell Performance and of Thermal and Water Management; and (5) Engineering Design and Development of Multicell Stacks. The accomplishments on these tasks may be summarized as follows: (1) A microelectrode technique was developed to determine the electrode kinetic parameters for the fuel cell reactions and mass transport parameters for the H2 and O2 reactants in the proton conducting membrane. (2) High energy efficiencies and high power densities were demonstrated in PEMFCs with low platinum loading electrodes (0.4 mg/cm(exp 2) or less), advanced membranes and optimized structures of membrane and electrode assemblies, as well as operating conditions. (3) The modeling analyses revealed methods to minimize mass transport limitations, particularly with air as the cathodic reactant; and for efficient thermal and water management. (4) Work is in progress to develop multi-kilowatt stacks with the electrodes containing low platinum loadings.

Uniform and accelerated degradation of pure iron patterned by Pt disc arrays

PubMed Central

Huang, Tao; Zheng, Yufeng

2016-01-01

Pure iron has been confirmed as a promising biodegradable metal. However, the degradation rate of pure iron should be accelerated to meet the clinical requirements. In this work, two different designs of platinum disc arrays, including sizes of Φ20 μm × S5 μm and Φ4 μm × S4 μm, have been coated on the surface of pure iron. Corrosion tests showed the platinum discs formed plenty of galvanic cells with the iron matrix which significantly accelerated the degradation of pure iron. Simultaneously, due to the designability of the shape, size as well as distribution of Pt discs, the degradation rate as well as degradation uniformity of pure iron can be effectively controlled by coating with platinum discs. The cytotoxicity test results unveiled that Pt discs patterned pure iron exhibited almost no toxicity to human umbilical vein endothelial cells, but a significant inhibition on proliferation of vascular smooth muscle cells. In addition, the hemolysis rate of Pt discs patterned pure iron was lower than 1%. Moreover, Pt discs also effectively reduced the number of adhered platelets. All these results indicated that Pt discs patterning is an effective way to accelerate degradation and improve biocompatibility of pure iron. PMID:27033380

The platinum microelectrode/Nafion interface - An electrochemical impedance spectroscopic analysis of oxygen reduction kinetics and Nafion characteristics

NASA Technical Reports Server (NTRS)

Parthasarathy, Arvind; Dave, Bhasker; Srinivasan, Supramaniam; Appleby, John A.; Martin, Charles R.

1992-01-01

The objectives of this study were to use electrochemical impedance spectroscopy (EIS) to study the oxygen-reduction reaction under lower humidification conditions than previously studied. The EIS technique permits the discrimination of electrode kinetics of oxygen reduction, mass transport of O2 in the membrane, and the electrical characteristics of the membrane. Electrode-kinetic parameters for the oxygen-reduction reaction, corrosion current densities for Pt, and double-layer capacitances were calculated. The production of water due to electrochemical reduction of oxygen greatly influenced the EIS response and the electrode kinetics at the Pt/Nafion interface. From the finite-length Warburg behavior, a measure of the diffusion coefficient of oxygen in Nafion and diffusion-layer thickness was obtained. An analysis of the EIS data in the high-frequency domain yielded membrane and interfacial characteristics such as ionic conductivity of the membrane, membrane grain-boundary capacitance and resistance, and uncompensated resistance.

Anthro-Centric Multisensory Interface for Vision Augmentation/Substitution (ACMI-VAS)

DTIC Science & Technology

2014-02-01

Argus™ I and II Retinal Prosthesis System epiretinal microelectrode arrays (Second Sight Medical Products, Inc, Sylmar, CA) recently approved for use in...Figure 3. C olour photo of A rgus II epiretinal prosthesis secured to the retina w ith a retinaltack. Figure 4. Subject using the A rgus II device perform...in the environment. Alternatively, we have also implemented a touch screen mechanism that allows the user to feel the pixels under his or her

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

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

Multilayer poly(3,4-ethylenedioxythiophene)-dexamethasone and poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate-carbon nanotubes coatings on glassy carbon microelectrode arrays for controlled drug release.

PubMed

Castagnola, Elisa; Carli, Stefano; Vomero, Maria; Scarpellini, Alice; Prato, Mirko; Goshi, Noah; Fadiga, Luciano; Kassegne, Sam; Ricci, Davide

2017-07-13

The authors present an electrochemically controlled, drug releasing neural interface composed of a glassy carbon (GC) microelectrode array combined with a multilayer poly(3,4-ethylenedioxythiophene) (PEDOT) coating. The system integrates the high stability of the GC electrode substrate, ideal for electrical stimulation and electrochemical detection of neurotransmitters, with the on-demand drug-releasing capabilities of PEDOT-dexamethasone compound, through a mechanically stable interlayer of PEDOT-polystyrene sulfonate (PSS)-carbon nanotubes (CNT). The authors demonstrate that such interlayer improves both the mechanical and electrochemical properties of the neural interface, when compared with a single PEDOT-dexamethasone coating. Moreover, the multilayer coating is able to withstand 10 × 10 6 biphasic pulses and delamination test with negligible change to the impedance spectra. Cross-section scanning electron microscopy images support that the PEDOT-PSS-CNT interlayer significantly improves the adhesion between the GC substrate and PEDOT-dexamethasone coating, showing no discontinuities between the three well-interconnected layers. Furthermore, the multilayer coating has superior electrochemical properties, in terms of impedance and charge transfer capabilities as compared to a single layer of either PEDOT coating or the GC substrate alone. The authors verified the drug releasing capabilities of the PEDOT-dexamethasone layer when integrated into the multilayer interface through repeated stimulation protocols in vitro, and found a pharmacologically relevant release of dexamethasone.

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

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.

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.

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.

Thin-film-transistor array: an exploratory attempt for high throughput cell manipulation using electrowetting principle

NASA Astrophysics Data System (ADS)

Shaik, F. Azam; Cathcart, G.; Ihida, S.; Lereau-Bernier, M.; Leclerc, E.; Sakai, Y.; Toshiyoshi, H.; Tixier-Mita, A.

2017-05-01

In lab-on-a-chip (LoC) devices, microfluidic displacement of liquids is a key component. electrowetting on dielectric (EWOD) is a technique to move fluids, with the advantage of not requiring channels, pumps or valves. Fluids are discretized into droplets on microelectrodes and moved by applying an electric field via the electrodes to manipulate the contact angle. Micro-objects, such as biological cells, can be transported inside of these droplets. However, the design of conventional microelectrodes, made by standard micro-fabrication techniques, fixes the path of the droplets, and limits the reconfigurability of paths and thus limits the parallel processing of droplets. In that respect, thin film transistor (TFT) technology presents a great opportunity as it allows infinitely reconfigurable paths, with high parallelizability. We propose here to investigate the possibility of using TFT array devices for high throughput cell manipulation using EWOD. A COMSOL based 2D simulation coupled with a MATLAB algorithm was used to simulate the contact angle modulation, displacement and mixing of droplets. These simulations were confirmed by experimental results. The EWOD technique was applied to a droplet of culture medium containing HepG2 carcinoma cells and demonstrated no negative effects on the viability of the cells. This confirms the possibility of applying EWOD techniques to cellular applications, such as parallel cell analysis.

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

PubMed

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

2006-01-01

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

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.

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

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.

M13 bacteriophage displaying DOPA on surfaces: fabrication of various nanostructured inorganic materials without time-consuming screening processes.

PubMed

Park, Joseph P; Do, Minjae; Jin, Hyo-Eon; Lee, Seung-Wuk; Lee, Haeshin

2014-01-01

M13 bacteriophage (phage) was engineered for the use as a versatile template for preparing various nanostructured materials via genetic engineering coupled to enzymatic chemical conversions. First, we engineered the M13 phage to display TyrGluGluGlu (YEEE) on the pVIII coat protein and then enzymatically converted the Tyr residue to 3,4-dihydroxyl-l-phenylalanine (DOPA). The DOPA-displayed M13 phage could perform two functions: assembly and nucleation. The engineered phage assembles various noble metals, metal oxides, and semiconducting nanoparticles into one-dimensional arrays. Furthermore, the DOPA-displayed phage triggered the nucleation and growth of gold, silver, platinum, bimetallic cobalt-platinum, and bimetallic iron-platinum nanowires. This versatile phage template enables rapid preparation of phage-based prototype devices by eliminating the screening process, thus reducing effort and time.

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.

Fabrication and characterization of microsieve electrode array (µSEA) enabling cell positioning on 3D electrodes

NASA Astrophysics Data System (ADS)

Schurink, B.; Tiggelaar, R. M.; Gardeniers, J. G. E.; Luttge, R.

2017-01-01

Here the fabrication and characterization of a novel microelectrode array for electrophysiology applications is described, termed a micro sieve electrode array (µSEA). This silicon based µSEA device allows for hydrodynamic parallel positioning of single cells on 3D electrodes realized on the walls of inverted pyramidal shaped pores. To realize the µSEA, a previously realized silicon sieving structure is provided with a patterned boron doped poly-silicon, connecting the contact electrodes with the 3D sensing electrodes in the pores. A LPCVD silicon-rich silicon nitride layer was used as insulation. The selective opening of this insulation layer at the ends of the wiring lines allows to generate well-defined contact and sensing electrodes according to the layout used in commercial microelectrode array readers. The main challenge lays in the simultaneously selective etching of material at both the planar surface (contact electrode) as well as in the sieving structure containing the (3D) pores (sensing electrodes). For the generation of 3D electrodes in the pores a self-aligning technique was developed using the pore geometry to our advantage. This technique, based on sacrificial layer etching, allows for the fine tuning of the sensing electrode surface area and thus supports the positioning and coupling of single cells on the electrode surface in relation to the cell size. Furthermore, a self-aligning silicide is formed on the sensing electrodes to favour the electrical properties. Experiments were performed to demonstrate the working principle of the µSEA using different types of neuronal cells. Capture efficiency in the pores was  >70% with a 70% survival rate of the cell maintained for up to 14 DIV. The TiSi2-boron-doped-poly-silicon sensing electrodes of the µSEA were characterized, which indicated noise levels of  <15 µV and impedance values of 360 kΩ. These findings potentially allow for future electrophysiological measurements using the µSEA.

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.

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.

Application of an e-tongue to the analysis of monovarietal and blends of white wines.

PubMed

Gutiérrez, Manuel; Llobera, Andreu; Ipatov, Andrey; Vila-Planas, Jordi; Mínguez, Santiago; Demming, Stefanie; Büttgenbach, Stephanus; Capdevila, Fina; Domingo, Carme; Jiménez-Jorquera, Cecilia

2011-01-01

This work presents a multiparametric system capable of characterizing and classifying white wines according to the grape variety and geographical origin. Besides, it quantifies specific parameters of interest for quality control in wine. The system, known as a hybrid electronic tongue, consists of an array of electrochemical microsensors-six ISFET based sensors, a conductivity sensor, a redox potential sensor and two amperometric electrodes, a gold microelectrode and a microelectrode for sensing electrochemical oxygen demand--and a miniaturized optofluidic system. The test sample set comprised eighteen Catalan monovarietal white wines from four different grape varieties, two Croatian monovarietal white wines and seven bi- and trivarietal mixtures prepared from the Catalan varieties. Different chemometric tools were used to characterize (i.e., Principal Component Analysis), classify (i.e., Soft Independent Modeling Class Analogy) and quantify (i.e., Partial-Least Squares) some parameters of interest. The results demonstrate the usefulness of the multisensor system for analysis of wine.

Application of an E-Tongue to the Analysis of Monovarietal and Blends of White Wines

PubMed Central

Gutiérrez, Manuel; Llobera, Andreu; Ipatov, Andrey; Vila-Planas, Jordi; Mínguez, Santiago; Demming, Stefanie; Büttgenbach, Stephanus; Capdevila, Fina; Domingo, Carme; Jiménez-Jorquera, Cecilia

2011-01-01

This work presents a multiparametric system capable of characterizing and classifying white wines according to the grape variety and geographical origin. Besides, it quantifies specific parameters of interest for quality control in wine. The system, known as a hybrid electronic tongue, consists of an array of electrochemical microsensors—six ISFET based sensors, a conductivity sensor, a redox potential sensor and two amperometric electrodes, a gold microelectrode and a microelectrode for sensing electrochemical oxygen demand—and a miniaturized optofluidic system. The test sample set comprised eighteen Catalan monovarietal white wines from four different grape varieties, two Croatian monovarietal white wines and seven bi- and trivarietal mixtures prepared from the Catalan varieties. Different chemometric tools were used to characterize (i.e., Principal Component Analysis), classify (i.e., Soft Independent Modeling Class Analogy) and quantify (i.e., Partial-Least Squares) some parameters of interest. The results demonstrate the usefulness of the multisensor system for analysis of wine. PMID:22163879

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.

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.

Microfabrication of an Implantable silicone Microelectrode array for an epiretinal prosthesis

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

Maghribi, Mariam Nader

2003-06-10

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

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

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.

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.

Development of three-dimension microelectrode array for bioelectric measurement using the liquidmetal-micromolding technique

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

Liu, Ran, E-mail: liuran@tsinghua.edu.cn; Yang, Xueyao; Chen, Weixing

2013-11-04

A method of manufacturing three-dimension microneedle electrode arrays is presented in this paper using the micromolding technology with liquid metal at room temperature, based on the physical property of the Bi-In-Sn liquid metal alloy, being its melting point especially low. Observed under scanning electron microscopy, the needle body of the electrode chip manufactured using this method has a good consistency. Skin penetration test in-vitro indicates that the microneedle electrode can pierce the stratum corneum and cross the high-impedance layer to acquire electrical signals. Electrical impedance and polarization voltage experimental results show that the electrode chips have great electric characteristics andmore » meet the practical application demands.« less

Three-dimensional neural cultures produce networks that mimic native brain activity.

PubMed

Bourke, Justin L; Quigley, Anita F; Duchi, Serena; O'Connell, Cathal D; Crook, Jeremy M; Wallace, Gordon G; Cook, Mark J; Kapsa, Robert M I

2018-02-01

Development of brain function is critically dependent on neuronal networks organized through three dimensions. Culture of central nervous system neurons has traditionally been limited to two dimensions, restricting growth patterns and network formation to a single plane. Here, with the use of multichannel extracellular microelectrode arrays, we demonstrate that neurons cultured in a true three-dimensional environment recapitulate native neuronal network formation and produce functional outcomes more akin to in vivo neuronal network activity. Copyright © 2017 John Wiley & Sons, Ltd.

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.

Tungsten trioxide nanoplate array supported platinum as a highly efficient counter electrode for dye-sensitized solar cells

NASA Astrophysics Data System (ADS)

Song, Dandan; Cui, Peng; Zhao, Xing; Li, Meicheng; Chu, Lihua; Wang, Tianyue; Jiang, Bing

2015-03-01

A tungsten trioxide (WO3) nanoplate array is fabricated directly on the FTO/glass substrate and used as a platinum (Pt) nanoscale supporter for a highly efficient and low Pt-consumption counter electrode (CE) in dye-sensitized solar cells (DSCs). A Pt/WO3 composite structure, with Pt nanoparticles having a diameter of 2-3 nm, increases the electrochemical catalytic activity in catalyzing the reduction of triiodide. Accordingly, the power conversion efficiency is increased from less than 1% for WO3 CE and 8.1% for Pt CE, respectively, to 8.9% for Pt/WO3 CE. Moreover, the use of Pt/WO3 CE can dramatically reduce the consumption of scarce Pt material, with a relatively low Pt-loading of ~2 μg cm-2, while maintaining a much better performance. The excellent performance of Pt/WO3 CE is attributed to the efficient electron injection and transport via WO3 supporters, as well as the nanostructure array morphology of WO3 for deposition of fine Pt nanoparticles. This work provides an approach for developing highly catalytic and low-cost Pt based CEs, which also has implications for the development of Pt/WO3 nanoplate arrays for other applications.A tungsten trioxide (WO3) nanoplate array is fabricated directly on the FTO/glass substrate and used as a platinum (Pt) nanoscale supporter for a highly efficient and low Pt-consumption counter electrode (CE) in dye-sensitized solar cells (DSCs). A Pt/WO3 composite structure, with Pt nanoparticles having a diameter of 2-3 nm, increases the electrochemical catalytic activity in catalyzing the reduction of triiodide. Accordingly, the power conversion efficiency is increased from less than 1% for WO3 CE and 8.1% for Pt CE, respectively, to 8.9% for Pt/WO3 CE. Moreover, the use of Pt/WO3 CE can dramatically reduce the consumption of scarce Pt material, with a relatively low Pt-loading of ~2 μg cm-2, while maintaining a much better performance. The excellent performance of Pt/WO3 CE is attributed to the efficient electron injection and transport via WO3 supporters, as well as the nanostructure array morphology of WO3 for deposition of fine Pt nanoparticles. This work provides an approach for developing highly catalytic and low-cost Pt based CEs, which also has implications for the development of Pt/WO3 nanoplate arrays for other applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr06787h

Flexible retinal electrode array

DOEpatents

Okandan, Murat [Albuquerque, NM; Wessendorf, Kurt O [Albuquerque, NM; Christenson, Todd R [Albuquerque, NM

2006-10-24

An electrode array which has applications for neural stimulation and sensing. The electrode array can include a large number of electrodes each of which is flexibly attached to a common substrate using a plurality of springs to allow the electrodes to move independently. The electrode array can be formed from a combination of bulk and surface micromachining, with electrode tips that can include an electroplated metal (e.g. platinum, iridium, gold or titanium) or a metal oxide (e.g. iridium oxide) for biocompatibility. The electrode array can be used to form a part of a neural prosthesis, and is particularly well adapted for use in an implantable retinal prosthesis where the electrodes can be tailored to provide a uniform gentle contact pressure with optional sensing of this contact pressure at one or more of the electrodes.

Characterization of the in vitro propagation of epileptiform electrophysiological activity in organotypic hippocampal slice cultures coupled to 3D microelectrode arrays.

PubMed

Pisciotta, Marzia; Morgavi, Giovanna; Jahnsen, Henrik

2010-10-28

Dynamic aspects of the propagation of epileptiform activity have so far received little attention. With the aim of providing new insights about the spatial features of the propagation of epileptic seizures in the nervous system, we studied in vitro the initiation and propagation of traveling epileptiform waves of electrophysiological activity in the hippocampus by means of substrate three-dimensional microelectrode arrays (MEAs) for extracellular measurements. Pharmacologically disinhibited hippocampal slices spontaneously generate epileptiform bursts mostly originating in CA3 and propagating to CA1. Our study specifically addressed the activity-dependent changes of the propagation of traveling electrophysiological waves in organotypic hippocampal slices during epileptiform discharge and in particular our question is: what happens to the epileptic signals during their propagation through the slice? Multichannel data analysis enabled us to quantify an activity-dependent increase in the propagation velocity of spontaneous bursts. Moreover, through the evaluation of the coherence of the signals, it was possible to point out that only the lower-frequency components (<95Hz) of the electrical activity are completely coherent with respect to the activity originating in the CA3, while components at higher frequencies lose the coherence, possibly suggesting that the cellular mechanism mediating propagation of electrophysiological activity becomes ineffective for those firing rates exceeding an upper bound or that some noise of neuronal origin was added to the signal during propagation. Copyright © 2010 Elsevier B.V. All rights reserved.

Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology.

PubMed

Napoli, Alessandro; Obeid, Iyad

2016-03-01

Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.

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.

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.

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.

Incubator-independent cell-culture perfusion platform for continuous long-term microelectrode array electrophysiology and time-lapse imaging

PubMed Central

Saalfrank, Dirk; Konduri, Anil Krishna; Latifi, Shahrzad; Habibey, Rouhollah; Golabchi, Asiyeh; Martiniuc, Aurel Vasile; Knoll, Alois; Ingebrandt, Sven; Blau, Axel

2015-01-01

Most in vitro electrophysiology studies extract information and draw conclusions from representative, temporally limited snapshot experiments. This approach bears the risk of missing decisive moments that may make a difference in our understanding of physiological events. This feasibility study presents a simple benchtop cell-culture perfusion system adapted to commercial microelectrode arrays (MEAs), multichannel electrophysiology equipment and common inverted microscopy stages for simultaneous and uninterrupted extracellular electrophysiology and time-lapse imaging at ambient CO2 levels. The concept relies on a transparent, replica-casted polydimethylsiloxane perfusion cap, gravity- or syringe-pump-driven perfusion and preconditioning of pH-buffered serum-free cell-culture medium to ambient CO2 levels at physiological temperatures. The low-cost microfluidic in vitro enabling platform, which allows us to image cultures immediately after cell plating, is easy to reproduce and is adaptable to the geometries of different cell-culture containers. It permits the continuous and simultaneous multimodal long-term acquisition or manipulation of optical and electrophysiological parameter sets, thereby considerably widening the range of experimental possibilities. Two exemplary proof-of-concept long-term MEA studies on hippocampal networks illustrate system performance. Continuous extracellular recordings over a period of up to 70 days revealed details on both sudden and gradual neural activity changes in maturing cell ensembles with large intra-day fluctuations. Correlated time-lapse imaging unveiled rather static macroscopic network architectures with previously unreported local morphological oscillations on the timescale of minutes. PMID:26543581

Composite Biomarkers Derived from Micro-Electrode Array Measurements and Computer Simulations Improve the Classification of Drug-Induced Channel Block.

PubMed

Tixier, Eliott; Raphel, Fabien; Lombardi, Damiano; Gerbeau, Jean-Frédéric

2017-01-01

The Micro-Electrode Array (MEA) device enables high-throughput electrophysiology measurements that are less labor-intensive than patch-clamp based techniques. Combined with human-induced pluripotent stem cells cardiomyocytes (hiPSC-CM), it represents a new and promising paradigm for automated and accurate in vitro drug safety evaluation. In this article, the following question is addressed: which features of the MEA signals should be measured to better classify the effects of drugs? A framework for the classification of drugs using MEA measurements is proposed. The classification is based on the ion channels blockades induced by the drugs. It relies on an in silico electrophysiology model of the MEA, a feature selection algorithm and automatic classification tools. An in silico model of the MEA is developed and is used to generate synthetic measurements. An algorithm that extracts MEA measurements features designed to perform well in a classification context is described. These features are called composite biomarkers. A state-of-the-art machine learning program is used to carry out the classification of drugs using experimental MEA measurements. The experiments are carried out using five different drugs: mexiletine, flecainide, diltiazem, moxifloxacin, and dofetilide. We show that the composite biomarkers outperform the classical ones in different classification scenarios. We show that using both synthetic and experimental MEA measurements improves the robustness of the composite biomarkers and that the classification scores are increased.

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.

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.

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.

Singlet and triplet excitation management in a bichromophoric near-infrared-phosphorescent BODIPY-benzoporphyrin platinum complex

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

Whited, M. T.; Djurovich, P. I.; Roberts, Sean T.

2011-01-12

Multichromophoric arrays provide one strategy for assembling molecules with intense absorptions across the visible spectrum but are generally focused on systems that efficiently produce and manipulate singlet excitations and therefore are burdened by the restrictions of (a) unidirectional energy transfer and (b) limited tunability of the lowest molecular excited state. In contrast, we present here a multichromophoric array based on four boron dipyrrins (BODIPY) bound to a platinum benzoporphyrin scaffold that exhibits intense panchromatic absorption and efficiently generates triplets. The spectral complementarity of the BODIPY and porphryin units allows the direct observation of fast bidirectional singlet and triplet energy transfermore » processes (k ST( 1BDP→ 1Por) = 7.8 × 10 11 s -1, k TT( 3Por→ 3BDP) = 1.0 × 10 10 s -1, k TT( 3BDP→ 3Por) = 1.6 × 10 10 s -1), leading to a long-lived equilibrated [ 3BDP][Por]⇌[BDP][ 3Por] state. This equilibrated state contains approximately isoenergetic porphyrin and BODIPY triplets and exhibits efficient near-infrared phosphorescence (λ em = 772 nm, Φ = 0.26). Taken together, these studies show that appropriately designed triplet-utilizing arrays may overcome fundamental limitations typically associated with core-shell chromophores by tunable redistribution of energy from the core back onto the antennae.« less

Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis

PubMed Central

Chen, Juan; Wang, Zhan; Zou, Ting; Cui, Jiajia; Yin, Jiye; Zheng, Wei; Jiang, Wuzhong; Zhou, Honghao; Liu, Zhaoqian

2016-01-01

Published data showed inconsistent results about associations of extensively studied polymorphisms with platinum-based chemotherapy response. Our study aimed to provide reliable conclusions of these associations by detecting genotypes of the SNPs in a larger sample size and summarizing a comprehensive pooled analysis. 13 SNPs in 8 genes were genotyped in 1024 NSCLC patients by SequenomMassARRAY. 39 published studies and our study were included in meta-analysis. Patients with GA or GG genotypes of XRCC1 G1196 had better response than AA genotype carriers (Genotyping study: OR = 0.72, 95%CI: 0.53-0.96, P = 0.028; Meta-analysis: OR = 0.74, 95%CI: 0.62-0.89, P = 0.001). Patients carrying CT or TT genotypes of XRCC1 C580T could be more sensitive to platinum-based chemotherapy compared to patients with CC genotype (OR = 0.54, 95%CI: 0.37-0.80, P = 0.002). CC genotype of XRCC3 C18067T carriers showed more resistance to platinum-based chemotherapy when compared to those with CT or TT genotypes (OR = 0.69, 95%CI: 0.52-0.91, P = 0.009). Our study indicated that XRCC1 G1196A/C580T and XRCC3 C18067T should be paid attention for personalized platinum-based chemotherapy in NSCLC patients. PMID:27248474

The development of a multichannel electrode array for retinal prostheses.

PubMed

Terasawa, Yasuo; Tashiro, Hiroyuki; Uehara, Akihiro; Saitoh, Tohru; Ozawa, Motoki; Tokuda, Takashi; Ohta, Jun

2006-01-01

The development of a multielectrode array is the key issue for retinal prostheses. We developed a 10 x 10 platinum electrode array that consists of an 8-microm polyimide layer sandwiched between 5-microm polymonochloro-para-xylylene (parylene-C) layers. Each electrode was formed as a 30-microm-high bump by Pt/Au double-layer electroplating. We estimated the charge delivery capability (CDC) of the electrode by measuring the CDCs of two-channel electrode arrays. The dimensions of each electrode of the two-channel array were the same as those of each electrode formed on the 10 x 10 array. The results suggest that for cathodic-first (CF) pulses, 80% of electrodes surpassed our development target of 318 microC/cm2, which corresponds to the charge density of pulses of 500 micros duration and 200 microA amplitude for a 200-microm-diameter planar electrode.

Enhanced electrochemical nanoring electrode for analysis of cytosol in single cells.

PubMed

Zhuang, Lihong; Zuo, Huanzhen; Wu, Zengqiang; Wang, Yu; Fang, Danjun; Jiang, Dechen

2014-12-02

A microelectrode array has been applied for single cell analysis with relatively high throughput; however, the cells were typically cultured on the microelectrodes under cell-size microwell traps leading to the difficulty in the functionalization of an electrode surface for higher detection sensitivity. Here, nanoring electrodes embedded under the microwell traps were fabricated to achieve the isolation of the electrode surface and the cell support, and thus, the electrode surface can be modified to obtain enhanced electrochemical sensitivity for single cell analysis. Moreover, the nanometer-sized electrode permitted a faster diffusion of analyte to the surface for additional improvement in the sensitivity, which was evidenced by the electrochemical characterization and the simulation. To demonstrate the concept of the functionalized nanoring electrode for single cell analysis, the electrode surface was deposited with prussian blue to detect intracellular hydrogen peroxide at a single cell. Hundreds of picoamperes were observed on our functionalized nanoring electrode exhibiting the enhanced electrochemical sensitivity. The success in the achievement of a functionalized nanoring electrode will benefit the development of high throughput single cell electrochemical analysis.

Selective labeling of retinal ganglion cells with calcium indicators by retrograde loading in vitro

PubMed Central

Behrend, Matthew R.; Ahuja, Ashish K.; Humayun, Mark S.; Weiland, James D.; Chow, Robert H.

2012-01-01

Here we present a retrograde loading technique that makes it possible for the first time to rapidly load a calcium indicator in the majority of retinal ganglion cells (RGCs) in salamander retina, and then to observe physiological activity of these dye-loaded cells. Dextran-conjugated calcium indicator, dissolved in water, was applied to the optic nerve stump. Following dye loading, the isolated retina was mounted on a microelectrode array to demonstrate that electrical activity and calcium activity were preserved, as the retina responded to electrical stimuli. PMID:19428523

Unitary Responses in Frog Olfactory Epithelium to Sterically Related Molecules at Low Concentrations

PubMed Central

Getchell, Thomas V.

1974-01-01

Responses of receptor cells in the frog's olfactory epithelium were recorded using platinum-black metal-filled microelectrodes. Spontaneous activity varied over a wide range from 0.07 to 1.8 spikes/s. Mean interspike intervals ranged from 13.7 to 0.5 s. Excitatory responses to six sterically related compounds at low concentrations were investigated. Stimuli were delivered in an aqueous medium. Thresholds for impulse initiation varied from greater than 1 mM down to the nanomolar concentration range. Thresholds of different olfactory receptors to the same stimulus could vary by several log units. Thresholds of the same receptor cell to different stimuli could be within the same order of magnitude, or could vary by as much as 5 log units. Based upon quantitative measures of stimulus-evoked excitatory responses it appeared that some receptors did not discriminate among sterically related molecules, whereas other receptors clearly discriminated between stimuli which evoke similar odor sensations. PMID:4211101

A novel versatile microbiosensor for local hydrogen detection by means of scanning photoelectrochemical microscopy.

PubMed

Zhao, Fangyuan; Conzuelo, Felipe; Hartmann, Volker; Li, Huaiguang; Stapf, Stefanie; Nowaczyk, Marc M; Rögner, Matthias; Plumeré, Nicolas; Lubitz, Wolfgang; Schuhmann, Wolfgang

2017-08-15

The development of a versatile microbiosensor for hydrogen detection is reported. Carbon-based microelectrodes were modified with a [NiFe]-hydrogenase embedded in a viologen-modified redox hydrogel for the fabrication of a sensitive hydrogen biosensor By integrating the microbiosensor in a scanning photoelectrochemical microscope, it was capable of serving simultaneously as local light source to initiate photo(bio)electrochemical reactions while acting as sensitive biosensor for the detection of hydrogen. A hydrogen evolution biocatalyst based on photosystem 1-platinum nanoparticle biocomplexes embedded into a specifically designed redox polymer was used as a model for proving the capability of the developed hydrogen biosensor for the detection of hydrogen upon localized illumination. The versatility and sensitivity of the proposed microbiosensor as probe tip allows simplification of the set-up used for the evaluation of complex electrochemical processes and the rapid investigation of local photoelectrocatalytic activity of biocatalysts towards light-induced hydrogen evolution. Copyright © 2017 Elsevier B.V. All rights reserved.

A new experimental device to evaluate eye ulcers using a multispectral electrical impedance technique

NASA Astrophysics Data System (ADS)

Bellotti, Mariela I.; Bast, Walter; Berra, Alejandro; Bonetto, Fabián J.

2011-07-01

We present a novel experimental technique to determine eye ulcers in animals using a spectral electrical impedance technique. We expect that this technique will be useful in dry eye syndrome. We used a sensor that is basically a platinum (Pt) microelectrode electrically insulated by glass from a cylindrical stainless steel counter-electrode. This sensor was applied to the naked eye of New Zealand rabbits (2.0-3.5 kg in weight). Whereas half of the eyes were normal (control), we applied to the remainder a few drops of 20% (v/v) alcohol to produce an ulcer in the eye. Using a multispectral electrical impedance system we measured ulcerated and control eyes and observed significant difference between normal and pathological samples. We also investigated the effects of different applied pressures and natural degradation of initially normal eyes as a function of time. We believe that this technique could be sufficiently sensitive and repetitive to help diagnose ocular surface diseases such as dry eye syndrome.

Manipulation of Microenvironment with a Built-in Electrochemical Actuator in Proximity of a Dissolved Oxygen Microsensor

NASA Technical Reports Server (NTRS)

Kim, Chang-Soo; Lee, Cae-Hyang; Fiering, Jason O.; Ufer, Stefan; Scarantino, Charles W.; Nagle, H. Troy; Fiering, Jason O.; Ufer, Stefan; Nagle, H. Troy; Scarantino, Charles W.

2004-01-01

Abstract - Biochemical sensors for continuous monitoring require dependable periodic self- diagnosis with acceptable simplicity to check its functionality during operation. An in situ self- diagnostic technique for a dissolved oxygen microsensor is proposed in an effort to devise an intelligent microsensor system with an integrated electrochemical actuation electrode. With a built- in platinum microelectrode that surrounds the microsensor, two kinds of microenvironments, called the oxygen-saturated or oxygen-depleted phases, can be created by water electrolysis depending on the polarity. The functionality of the microsensor can be checked during these microenvironment phases. The polarographic oxygen microsensor is fabricated on a flexible polyimide substrate (Kapton) and the feasibility of the proposed concept is demonstrated in a physiological solution. The sensor responds properly during the oxygen-generating and oxygen- depleting phases. The use of these microenvironments for in situ self-calibration is discussed to achieve functional integration as well as structural integration of the microsensor system.

A new experimental device to evaluate eye ulcers using a multispectral electrical impedance technique.

PubMed

Bellotti, Mariela I; Bast, Walter; Berra, Alejandro; Bonetto, Fabián J

2011-07-01

We present a novel experimental technique to determine eye ulcers in animals using a spectral electrical impedance technique. We expect that this technique will be useful in dry eye syndrome. We used a sensor that is basically a platinum (Pt) microelectrode electrically insulated by glass from a cylindrical stainless steel counter-electrode. This sensor was applied to the naked eye of New Zealand rabbits (2.0-3.5 kg in weight). Whereas half of the eyes were normal (control), we applied to the remainder a few drops of 20% (v/v) alcohol to produce an ulcer in the eye. Using a multispectral electrical impedance system we measured ulcerated and control eyes and observed significant difference between normal and pathological samples. We also investigated the effects of different applied pressures and natural degradation of initially normal eyes as a function of time. We believe that this technique could be sufficiently sensitive and repetitive to help diagnose ocular surface diseases such as dry eye syndrome.

Rheotaxis of elongated platinum-gold nanoswimmers

NASA Astrophysics Data System (ADS)

Brosseau, Quentin; Wu, Yang; Ristroph, Leif; Zhang, Jun; Ward, Michael; Shelley, Michael

2017-11-01

Directed motion of self-propelled colloids has attracted much attention as a possible means to transport microscopic cargo to desired locations. However, active colloids, such as our gold-platinum (Au-Pt) bi-metallic motors ( 2 micrometers) that are powered by hydrogen peroxide (H2O2), are subjected to Brownian motion and move diffusively. These swimmers can be directed via interactions with structured substrates, e.g. within an array of asymmetric pillars. Our current study focuses on realizing the directed motion in an imposed open flow, of these active nanorods. This dynamic response, often referred to as ``rheotaxis'', is found in many marine organisms. The effect of flow geometry and flow characteristics will be discussed in more details.

Experimental observation of the thermocapillary driven motion of bubbles in a molten glass under low gravity conditions

NASA Technical Reports Server (NTRS)

Smith, H. D.; Mattox, D. M.; Wilcox, W. R.; Subramanian, R. S.; Meyyappan, M.

1982-01-01

An experiment was carried out on board a Space Processing Applications Rocket with the aim of demonstrating bubble migration in molten glass due to a temperature gradient under low gravity conditions. During the flight, a sample of a sodium borate melt with a specific bubble array, contained in a platinum/fused silica cell, was subjected to a well defined temperature gradient for more than 4 minutes. Photographs taken at one second intervals during the experiment clearly show that the bubbles move toward the hot spot on the platinum heater strip. This result is consistent with the predictions of the theory of thermocapillary driven bubble motion.

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

SU-F-I-56: High-Precision Gamma-Ray Analysis of Medical Isotopes

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

Chopra, N; Chillery, T; Chowdhury, P

2016-06-15

Purpose: Advanced, time-resolved, Compton-suppressed gamma-ray spectroscopy with germanium detectors is implemented for assaying medical isotopes to study the radioactive decay process leading to a more accurate appraisal of the received dose and treatment planning. Lowell’s Array for Radiological Assay (LARA), a detector array that is comprised of six Compton-suppressed high-purity germanium detectors, is currently under development at UMass-Lowell which combines Compton-suppression and time-and-angle correlations to allow for highly efficient and highly sensitive measurements. Methods: Two isotopes produced Brookhaven Linac Isotope Producer (BLIP) were investigated. {sup 82}Sr which is the parent isotope for producing {sup 82}Rb is often used in cardiacmore » PET. {sup 82}Sr gamma-ray spectrum is dominated by the 511keV photons from positron annihilation which prevent precise measurement of co-produced contaminant isotopes. A second project was to investigate the production of platinum isotopes. Natural platinum was bombarded with protons from 53MeV to 200MeV. The resulting spectrum was complicated due to the large number of stable platinum isotopes in the target, the variety of open reaction channels (p,xn), (p,pxn), (p,axn). Results: By using face-to-face NaI(Tl) counters 90-degrees to the Compton-suppressed germaniums to detect the 511keV photons, a much cleaner and more sensitive measurement of {sup 85}Sr and other contaminants was obtained. For the platinum target, we identified the production of {sup 188–189–191–195}Pt, {sup 191–192–193–194–195–196}Au and {sup 186–188–189–190–192–194–189–190–192–194}Ir. For example, at the lower energies (53 and 65MeV), we measured {sup 191}Pt production cross-sections of 144mb and 157mb. Considerable care was needed in following the process of dissolving and diluting the samples to get consistent results. The new LARA array will help us better ascertain the absolute efficiency of the counting system and more reliable production cross-sections. Conclusion: Modern HPGe spectroscopic techniques provide enhanced sensitivity, promising precise quantification of the quality of radioisotopes used in medical physics. Using new decay information may have non-trivial impact on treatment planning and dose-assessment.« less

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.

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

NASA Astrophysics Data System (ADS)

Roshani, Amir; Erfanian, Abbas

2016-08-01

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

Bio-inspired routes for synthesizing efficient nanoscale platinum electrocatalysts

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

Cha, Jennifer N.; Wang, Joseph

2014-08-31

The overall objective of the proposed research is to use fundamental advances in bionanotechnology to design powerful platinum nanocrystal electrocatalysts for fuel cell applications. The new economically-viable, environmentally-friendly, bottom-up biochemical synthetic strategy will produce platinum nanocrystals with tailored size, shape and crystal orientation, hence leading to a maximum electrochemical reactivity. There are five specific aims to the proposed bio-inspired strategy for synthesizing efficient electrocatalytic platinum nanocrystals: (1) isolate peptides that both selectively bind particular crystal faces of platinum and promote the nucleation and growth of particular nanocrystal morphologies, (2) pattern nanoscale 2-dimensional arrays of platinum nucleating peptides from DNA scaffolds,more » (3) investigate the combined use of substrate patterned peptides and soluble peptides on nanocrystal morphology and growth (4) synthesize platinum crystals on planar and large-area carbon electrode supports, and (5) perform detailed characterization of the electrocatalytic behavior as a function of catalyst size, shape and morphology. Project Description and Impact: This bio-inspired collaborative research effort will address key challenges in designing powerful electrocatalysts for fuel cell applications by employing nucleic acid scaffolds in combination with peptides to perform specific, environmentally-friendly, simultaneous bottom-up biochemical synthesis and patterned assembly of highly uniform and efficient platinum nanocrystal catalysts. Bulk synthesis of nanoparticles usually produces a range of sizes, accessible catalytic sites, crystal morphologies, and orientations, all of which lead to inconsistent catalytic activities. In contrast, biological systems routinely demonstrate exquisite control over inorganic syntheses at neutral pH and ambient temperature and pressures. Because the orientation and arrangement of the templating biomolecules can be precisely controlled, the nanocrystals boast a defined shape, morphology, orientation and size and are synthesized at benign reaction conditions. Adapting the methods of biomineralization towards the synthesis of platinum nanocrystals will allow effective control at a molecular level of the synthesis of highly active metal electrocatalysts, with readily tailored properties, through tuning of the biochemical inputs. The proposed research will incorporate many facets of biomineralization by: (1) isolating peptides that selectively bind particular crystal faces of platinum (2) isolating peptides that promote the nucleation and growth of particular nanocrystal morphologies (3) using two-dimensional DNA scaffolds to control the spatial orientation and density of the platinum nucleating peptides, and (4) combining bio-templating and soluble peptides to control crystal nucleation, orientation, and morphology. The resulting platinum nanocrystals will be evaluated for their electrocatalytic behavior (on common carbon supports) to determine their optimal size, morphology and crystal structure. We expect that such rational biochemical design will lead to highly uniform and efficient platinum nanocrystal catalysts for fuel cell applications.« less

Numerical Simulation of the Diffusion Processes in Nanoelectrode Arrays Using an Axial Neighbor Symmetry Approximation.

PubMed

Peinetti, Ana Sol; Gilardoni, Rodrigo S; Mizrahi, Martín; Requejo, Felix G; González, Graciela A; Battaglini, Fernando

2016-06-07

Nanoelectrode arrays have introduced a complete new battery of devices with fascinating electrocatalytic, sensitivity, and selectivity properties. To understand and predict the electrochemical response of these arrays, a theoretical framework is needed. Cyclic voltammetry is a well-fitted experimental technique to understand the undergoing diffusion and kinetics processes. Previous works describing microelectrode arrays have exploited the interelectrode distance to simulate its behavior as the summation of individual electrodes. This approach becomes limited when the size of the electrodes decreases to the nanometer scale due to their strong radial effect with the consequent overlapping of the diffusional fields. In this work, we present a computational model able to simulate the electrochemical behavior of arrays working either as the summation of individual electrodes or being affected by the overlapping of the diffusional fields without previous considerations. Our computational model relays in dividing a regular electrode array in cells. In each of them, there is a central electrode surrounded by neighbor electrodes; these neighbor electrodes are transformed in a ring maintaining the same active electrode area than the summation of the closest neighbor electrodes. Using this axial neighbor symmetry approximation, the problem acquires a cylindrical symmetry, being applicable to any diffusion pattern. The model is validated against micro- and nanoelectrode arrays showing its ability to predict their behavior and therefore to be used as a designing tool.

Electronic nanobiosensors based on two-dimensional materials

NASA Astrophysics Data System (ADS)

Ping, Jinglei

Atomically-thick two-dimensional (2D) nanomaterials have tremendous potential to be applied as transduction elements in biosensors and bioelectronics. We developed scalable methods for synthesis and large-area transfer of two-dimensional nanomaterials, particularly graphene and metal dichalcogenides (so called ``MX2'' materials). We also developed versatile fabrication methods for large arrays of field-effect transistors (FETs) and micro-electrodes with these nanomaterials based on either conventional photolithography or innovative approaches that minimize contamination of the 2D layer. By functionalizing the FETs with a computationally redesigned water-soluble mu-opioid receptor, we created selective and sensitive biosensors suitable for detection of the drug target naltrexone and the neuropeptide enkephalin at pg/mL concentrations. We also constructed DNA-functionalized biosensors and nano-particle decorated biosensors by applying related bio-nano integration techniques. Our methodology paves the way for multiplexed nanosensor arrays with all-electronic readout suitable for inexpensive point-of-care diagnostics, drug-development and biomedical research. With graphene field-effect transistors, we investigated the graphene/solution interface and developed a quantitative model for the effect of ionic screening on the graphene carrier density based on theories of the electric double layer. Finally, we have developed a technique for measuring low-level Faradaic charge-transfer current (fA) across the graphene/solution interface via real-time charge monitoring of graphene microelectrodes in ionic solution. This technique enables the development of flexible and transparent pH sensors that are promising for in vivo applications. The author acknowledges the support from the Defense Advanced Research Projects Agency (DARPA) and the U. S. Army Research Office under Grant Number W911NF1010093.

Voltage-sensitive-dye imaging of microstimulation-evoked neural activity through intracortical horizontal and callosal connections in cat visual cortex.

PubMed

Suzurikawa, Jun; Tani, Toshiki; Nakao, Masayuki; Tanaka, Shigeru; Takahashi, Hirokazu

2009-12-01

Recently, intrinsic signal optical imaging has been widely used as a routine procedure for visualizing cortical functional maps. We do not, however, have a well-established imaging method for visualizing cortical functional connectivity indicating spatio-temporal patterns of activity propagation in the cerebral cortex. In the present study, we developed a novel experimental setup for investigating the propagation of neural activities combining the intracortical microstimulation (ICMS) technique with voltage sensitive dye (VSD) imaging, and demonstrated the feasibility of this setup applying to the measurement of time-dependent intra- and inter-hemispheric spread of ICMS-evoked excitation in the cat visual cortices, areas 17 and 18. A microelectrode array for the ICMS was inserted with a specially designed easy-to-detach electrode holder around the 17/18 transition zones (TZs), where the left and right hemispheres were interconnected via the corpus callosum. The microelectrode array was stably anchored in agarose without any holder, which enabled us to visualize evoked activities even in the vicinity of penetration sites as well as in a wide recording region that covered a part of both hemispheres. The VSD imaging could successfully visualize ICMS-evoked excitation and subsequent propagation in the visual cortices contralateral as well as ipsilateral to the ICMS. Using the orientation maps as positional references, we showed that the activity propagation patterns were consistent with previously reported anatomical patterns of intracortical and interhemispheric connections. This finding indicates that our experimental system can serve for the investigation of cortical functional connectivity.

Selection of a battery of rapid toxicity sensors for drinking water evaluation.

PubMed

van der Schalie, William H; James, Ryan R; Gargan, Thomas P

2006-07-15

Comprehensive identification of chemical contaminants in Army field water supplies can be a lengthy process, but rapid analytical methods suitable for field use are limited. A complementary approach is to directly measure toxicity instead of individual chemical constituents. Ten toxicity sensors utilizing enzymes, bacteria, or vertebrate cells were tested to determine the minimum number of sensors that could rapidly identify toxicity in water samples containing one of 12 industrial chemicals. The ideal sensor would respond at a concentration just exceeding the Military Exposure Guideline (MEG) level for the chemical (an estimated threshold for adverse effects) but below the human lethal concentration. Chemical solutions were provided to testing laboratories as blind samples. No sensors responded to deionized water blanks, and only one sensor responded to a hard water blank. No single toxicity sensor responded to more than six chemicals in the desired response range, and one chemical (nicotine) was not detected by any sensor with the desired sensitivity. A combination of three sensors (Microtox, the Electric Cell Substrate Impedance Sensing (ECIS) test, and the Hepatocyte low density lipoprotein (LDL) uptake test) responded appropriately to nine of twelve chemicals. Adding a fourth sensor (neuronal microelectrode array) to the test battery allowed detection of two additional chemicals (aldicarb and methamidophos), but the neuronal microelectrode array was overly sensitive to paraquat. Evaluating sensor performance using a standard set of chemicals and a desired sensitivity range provides a basis both for selecting among available toxicity sensors and for evaluating emerging sensor technologies. Recommendations for future toxicity sensor evaluations are discussed.

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

PubMed Central

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

2010-01-01

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

High-Density Droplet Microarray of Individually Addressable Electrochemical Cells.

PubMed

Zhang, Huijie; Oellers, Tobias; Feng, Wenqian; Abdulazim, Tarik; Saw, En Ning; Ludwig, Alfred; Levkin, Pavel A; Plumeré, Nicolas

2017-06-06

Microarray technology has shown great potential for various types of high-throughput screening applications. The main read-out methods of most microarray platforms, however, are based on optical techniques, limiting the scope of potential applications of such powerful screening technology. Electrochemical methods possess numerous complementary advantages over optical detection methods, including its label-free nature, capability of quantitative monitoring of various reporter molecules, and the ability to not only detect but also address compositions of individual compartments. However, application of electrochemical methods for the purpose of high-throughput screening remains very limited. In this work, we develop a high-density individually addressable electrochemical droplet microarray (eDMA). The eDMA allows for the detection of redox-active reporter molecules irrespective of their electrochemical reversibility in individual nanoliter-sized droplets. Orthogonal band microelectrodes are arranged to form at their intersections an array of three-electrode systems for precise control of the applied potential, which enables direct read-out of the current related to analyte detection. The band microelectrode array is covered with a layer of permeable porous polymethacrylate functionalized with a highly hydrophobic-hydrophilic pattern, forming spatially separated nanoliter-sized droplets on top of each electrochemical cell. Electrochemical characterization of single droplets demonstrates that the underlying electrode system is accessible to redox-active molecules through the hydrophilic polymeric pattern and that the nonwettable hydrophobic boundaries can spatially separate neighboring cells effectively. The eDMA technology opens the possibility to combine the high-throughput biochemical or living cell screenings using the droplet microarray platform with the sequential electrochemical read-out of individual droplets.

Interfacing 3D Engineered Neuronal Cultures to Micro-Electrode Arrays: An Innovative In Vitro Experimental Model.

PubMed

Tedesco, Mariateresa; Frega, Monica; Martinoia, Sergio; Pesce, Mattia; Massobrio, Paolo

2015-10-18

Currently, large-scale networks derived from dissociated neurons growing and developing in vitro on extracellular micro-transducer devices are the gold-standard experimental model to study basic neurophysiological mechanisms involved in the formation and maintenance of neuronal cell assemblies. However, in vitro studies have been limited to the recording of the electrophysiological activity generated by bi-dimensional (2D) neural networks. Nonetheless, given the intricate relationship between structure and dynamics, a significant improvement is necessary to investigate the formation and the developing dynamics of three-dimensional (3D) networks. In this work, a novel experimental platform in which 3D hippocampal or cortical networks are coupled to planar Micro-Electrode Arrays (MEAs) is presented. 3D networks are realized by seeding neurons in a scaffold constituted of glass microbeads (30-40 µm in diameter) on which neurons are able to grow and form complex interconnected 3D assemblies. In this way, it is possible to design engineered 3D networks made up of 5-8 layers with an expected final cell density. The increasing complexity in the morphological organization of the 3D assembly induces an enhancement of the electrophysiological patterns displayed by this type of networks. Compared with the standard 2D networks, where highly stereotyped bursting activity emerges, the 3D structure alters the bursting activity in terms of duration and frequency, as well as it allows observation of more random spiking activity. In this sense, the developed 3D model more closely resembles in vivo neural networks.

Interfacing 3D Engineered Neuronal Cultures to Micro-Electrode Arrays: An Innovative In Vitro Experimental Model

PubMed Central

Tedesco, Mariateresa; Frega, Monica; Martinoia, Sergio; Pesce, Mattia; Massobrio, Paolo

2015-01-01

Currently, large-scale networks derived from dissociated neurons growing and developing in vitro on extracellular micro-transducer devices are the gold-standard experimental model to study basic neurophysiological mechanisms involved in the formation and maintenance of neuronal cell assemblies. However, in vitro studies have been limited to the recording of the electrophysiological activity generated by bi-dimensional (2D) neural networks. Nonetheless, given the intricate relationship between structure and dynamics, a significant improvement is necessary to investigate the formation and the developing dynamics of three-dimensional (3D) networks. In this work, a novel experimental platform in which 3D hippocampal or cortical networks are coupled to planar Micro-Electrode Arrays (MEAs) is presented. 3D networks are realized by seeding neurons in a scaffold constituted of glass microbeads (30-40 µm in diameter) on which neurons are able to grow and form complex interconnected 3D assemblies. In this way, it is possible to design engineered 3D networks made up of 5-8 layers with an expected final cell density. The increasing complexity in the morphological organization of the 3D assembly induces an enhancement of the electrophysiological patterns displayed by this type of networks. Compared with the standard 2D networks, where highly stereotyped bursting activity emerges, the 3D structure alters the bursting activity in terms of duration and frequency, as well as it allows observation of more random spiking activity. In this sense, the developed 3D model more closely resembles in vivo neural networks. PMID:26554533

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.

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.

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 novel automated spike sorting algorithm with adaptable feature extraction.

PubMed

Bestel, Robert; Daus, Andreas W; Thielemann, Christiane

2012-10-15

To study the electrophysiological properties of neuronal networks, in vitro studies based on microelectrode arrays have become a viable tool for analysis. Although in constant progress, a challenging task still remains in this area: the development of an efficient spike sorting algorithm that allows an accurate signal analysis at the single-cell level. Most sorting algorithms currently available only extract a specific feature type, such as the principal components or Wavelet coefficients of the measured spike signals in order to separate different spike shapes generated by different neurons. However, due to the great variety in the obtained spike shapes, the derivation of an optimal feature set is still a very complex issue that current algorithms struggle with. To address this problem, we propose a novel algorithm that (i) extracts a variety of geometric, Wavelet and principal component-based features and (ii) automatically derives a feature subset, most suitable for sorting an individual set of spike signals. Thus, there is a new approach that evaluates the probability distribution of the obtained spike features and consequently determines the candidates most suitable for the actual spike sorting. These candidates can be formed into an individually adjusted set of spike features, allowing a separation of the various shapes present in the obtained neuronal signal by a subsequent expectation maximisation clustering algorithm. Test results with simulated data files and data obtained from chick embryonic neurons cultured on microelectrode arrays showed an excellent classification result, indicating the superior performance of the described algorithm approach. Copyright © 2012 Elsevier B.V. All rights reserved.

Optical coherence microscopy of mouse cortical vasculature surrounding implanted electrodes

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

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

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.

Single particle electrochemical sensors and methods of utilization

DOEpatents

Schoeniger, Joseph [Oakland, CA; Flounders, Albert W [Berkeley, CA; Hughes, Robert C [Albuquerque, NM; Ricco, Antonio J [Los Gatos, CA; Wally, Karl [Lafayette, CA; Kravitz, Stanley H [Placitas, NM; Janek, Richard P [Oakland, CA

2006-04-04

The present invention discloses an electrochemical device for detecting single particles, and methods for using such a device to achieve high sensitivity for detecting particles such as bacteria, viruses, aggregates, immuno-complexes, molecules, or ionic species. The device provides for affinity-based electrochemical detection of particles with single-particle sensitivity. The disclosed device and methods are based on microelectrodes with surface-attached, affinity ligands (e.g., antibodies, combinatorial peptides, glycolipids) that bind selectively to some target particle species. The electrodes electrolyze chemical species present in the particle-containing solution, and particle interaction with a sensor element modulates its electrolytic activity. The devices may be used individually, employed as sensors, used in arrays for a single specific type of particle or for a range of particle types, or configured into arrays of sensors having both these attributes.

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.

A titania nanotube-array room-temperature sensor for selective detection of hydrogen at low concentrations.

PubMed

Varghese, Oomman K; Mor, Gopal K; Grimes, Craig A; Paulose, Maggie; Mukherjee, Niloy

2004-09-01

A tremendous variation in electrical resistance, from the semiconductor to metallic range, has been observed in titania nanotube arrays at room temperature, approximately 25 degrees C, in the presence of < or = 1000 ppm hydrogen gas. The nanotube arrays are fabricated by anodizing titanium foil in an aqueous electrolyte solution containing hydrofluoric acid and acetic acid. Subsequently, the arrays are coated with a 10 nm layer of palladium by evaporation. Electrical contacts are made by sputtering a 2 mm diameter platinum disk atop the Pd-coated nanotube array. These sensors exhibit a resistance variation of the order of 10(4) in the presence of 100 ppm hydrogen at 25 degrees C. The sensors demonstrate complete reversibility, repeatability, high selectivity, negligible drift and wide dynamic range. The nanoscale geometry of the nanotubes, in particular the points of tube-to-tube contact, is believed to be responsible for the outstanding hydrogen gas sensitivities.

Potential for unreliable interpretation of EEG recorded with microelectrodes.

PubMed

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

2013-08-01

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

Platinum-Based Chemotherapy Induces Methylation Changes in Blood DNA Associated with Overall Survival in Patients with Ovarian Cancer.

PubMed

Flanagan, James M; Wilson, Angela; Koo, Chail; Masrour, Nahal; Gallon, John; Loomis, Erick; Flower, Kirsty; Wilhelm-Benartzi, Charlotte; Hergovich, Alexander; Cunnea, Paula; Gabra, Hani; Braicu, Elena Ioana; Sehouli, Jalid; Darb-Esfahani, Silvia; Vanderstichele, Adriaan; Vergote, Ignace; Kreuzinger, Caroline; Castillo-Tong, Dan Cacsire; Wisman, G Bea A; Berns, Els Mjj; Siddiqui, Nadeem; Paul, James; Brown, Robert

2017-05-01

Purpose: DNA damage repair can lead to epigenetic changes. DNA mismatch repair proteins bind to platinum DNA adducts and at sites of DNA damage can recruit the DNA methylating enzyme DNMT1, resulting in aberrant methylation. We hypothesised that DNA damage repair during platinum-based chemotherapy may cause aberrant DNA methylation in normal tissues of patients such as blood. Experimental Design: We used Illumina 450k methylation arrays and bisulphite pyrosequencing to investigate methylation at presentation and relapse in blood DNA from patients with ovarian cancer enrolled in the SCOTROC1 trial ( n = 247) and in a cohort of ovarian tumor DNA samples collected at first relapse ( n = 46). We used an ovarian cancer cell line model to investigate the role of the DNA mismatch repair gene MLH1 in platinum-induced methylation changes. Results: Specific CpG methylation changes in blood at relapse are observed following platinum-based chemotherapy and are associated with patient survival, independent of other clinical factors [hazard ratio, 3.7; 95% confidence interval, 1.8-7.6, P = 2.8 × 10 -4 ]. Similar changes occur in ovarian tumors at relapse, also associated with patient survival (hazard ratio, 2.6; 95% confidence interval, 1.0-6.8, P = 0.048). Using an ovarian cancer cell line model, we demonstrate that functional mismatch repair increases the frequency of platinum-induced methylation. Conclusions: DNA methylation in blood at relapse following chemotherapy, and not at presentation, is informative regarding survival of patients with ovarian cancer. Functional DNA mismatch repair increases the frequency of DNA methylation changes induced by platinum. DNA methylation in blood following chemotherapy could provide a noninvasive means of monitoring patients' epigenetic responses to treatment without requiring a tumor biopsy. Clin Cancer Res; 23(9); 2213-22. ©2016 AACR . ©2016 American Association for Cancer Research.

One-Step Formation of WO3-Loaded TiO2 Nanotubes Composite Film for High Photocatalytic Performance

PubMed Central

Lee, Wai Hong; Lai, Chin Wei; Abd Hamid, Sharifah Bee

2015-01-01

High aspect ratio of WO3-loaded TiO2 nanotube arrays have been successfully synthesized using the electrochemical anodization method in an ethylene glycol electrolyte containing 0.5 wt% ammonium fluoride in a range of applied voltage of 10–40 V for 30 min. The novelty of this research works in the one-step formation of WO3-loaded TiO2 nanotube arrays composite film by using tungsten as the cathode material instead of the conventionally used platinum electrode. As compared with platinum, tungsten metal has lower stability, forming dissolved ions (W6+) in the electrolyte. The W6+ ions then move towards the titanium foil and form a coherent deposit on titanium foil. By controlling the oxidation rate and chemical dissolution rate of TiO2 during the electrochemical anodization, the nanotubular structure of TiO2 film could be achieved. In the present study, nanotube arrays were characterized using FESEM, EDAX, XRD, as well as Raman spectroscopy. Based on the results obtained, nanotube arrays with average pore diameter of up to 74 nm and length of 1.6 µm were produced. EDAX confirmed the presence of tungsten element within the nanotube arrays which varied in content from 1.06 at% to 3.29 at%. The photocatalytic activity of the nanotube arrays was then investigated using methyl orange degradation under TUV 96W UV-B Germicidal light irradiation. The nanotube with the highest aspect ratio, geometric surface area factor and at% of tungsten exhibited the highest photocatalytic activity due to more photo-induced electron-hole pairs generated by the larger surface area and because WO3 improves charge separation, reduces charge carrier recombination and increases charge carrier lifetime via accumulation of electrons and holes in the two different metal oxide semiconductor components.

Array servo scanning micro EDM of 3D micro cavities

NASA Astrophysics Data System (ADS)

Tong, Hao; Li, Yong; Yi, Futing

2011-05-01

Micro electro discharge machining (Micro EDM) is a non-traditional processing technology with the special advantages of low set-up cost and few cutting force in machining any conductive materials regardless of their hardness. As well known, die-sinking EDM is unsuitable for machining the complex 3D micro cavity less than 1mm due to the high-priced fabrication of 3D microelectrode itself and its serous wear during EDM process. In our former study, a servo scanning 3D micro-EDM (3D SSMEDM) method was put forward, and our experiments showed it was available to fabricate complex 3D micro-cavities. In this study, in order to improve machining efficiency and consistency accuracy for array 3D micro-cavities, an array-servo-scanning 3D micro EDM (3D ASSMEDM) method is presented considering the complementary advantages of the 3D SSMEDM and the array micro electrodes with simple cross-section. During 3D ASSMEDM process, the array cavities designed by CAD / CAM system can be batch-manufactured by servo scanning layer by layer using array-rod-like micro tool electrodes, and the axial wear of the array electrodes is compensated in real time by keeping discharge gap. To verify the effectiveness of the 3D ASSMEDM, the array-triangle-micro cavities (side length 630 μm) are batch-manufactured on P-doped silicon by applying the array-micro-electrodes with square-cross-section fabricated by LIGA process. Our exploratory experiment shows that the 3D ASSMEDM provides a feasible approach for the batch-manufacture of 3D array-micro-cavities of conductive materials.

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

NASA Astrophysics Data System (ADS)

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

2017-08-01

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

Microelectrodes in microbial ecology

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

Boots, S.

1989-03-15

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

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

PubMed Central

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

2016-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2013-12-01

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

Electropolymerization of Uniform Polyaniline Nanorod Arrays on Conducting Oxides as Counter Electrodes in Dye-Sensitized Solar Cells.

PubMed

He, Ziming; Liu, Jing; Khoo, Si Yun; Tan, Timothy Thatt Yang

2016-01-01

Conventional techniques for the synthesis of oriented polyaniline (PANI) nanostructures are often complex or time consuming. Through an innovative reduced graphene oxide (rGO) modified FTO and a low-potential electropolymerization strategy, the rapid and template-free growth of a highly ordered PANI nanorod array on the FTO substrate is realized. The highly ordered nanostructure of the PANI array leads to a high electrocatalytic activity and chemical stability. The importance of the polymerization potential and rGO surface modification to achieve this nanostructure is revealed. Compared to platinum, the PANI nanorod array exhibits an enhanced performance and stability as counter electrodes in dye-sensitized solar cells, with a 17.6 % enhancement in power conversion efficiency. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

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

2015-01-01

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

Colloidal-gold electrosensor measuring device

DOEpatents

Wegner, S.; Harpold, M.A.; McCaffrey, T.M.; Morris, S.E.; Wojciechowski, M.; Zhao, J.; Henkens, R.W.; Naser, N.; O`Daly, J.P.

1995-11-21

The present invention provides a new device for use in measuring lead levels in biological and environmental samples. Using square wave coulometry and colloidal gold particles impregnated on carbon electrodes, the present invention provides a rapid, reliable, portable and inexpensive means of detecting low lead levels. The colloidal gold modified electrodes have microelectrode array characteristics and produce significantly higher stripping detection signals for lead than are produced at bulk gold electrode surfaces. The method is effective in determining levels of lead down to at least 5 {micro}g/dL in blood samples as small as 10 {micro}L. 9 figs.

Colloidal-gold electrosensor measuring device

DOEpatents

Wegner, Steven; Harpold, Michael A.; McCaffrey, Terence M.; Morris, Susan E.; Wojciechowski, Marek; Zhao, Junguo; Henkens, Robert W.; Naser, Najih; O'Daly, John P.

1995-01-01

The present invention provides a new device for use in measuring lead levels in biological and environmental samples. Using square wave coulometry and colloidal gold particles impregnated on carbon electrodes, the present invention provides a rapid, reliable, portable and inexpensive means of detecting low lead levels. The colloidal gold modified electrodes have microelectrode array characteristics and produce significantly higher stripping detection signals for lead than are produced at bulk gold electrode surfaces. The method is effective in determining levels of lead down to at least 5 .mu.g/dL in blood samples as small as 10 .mu.L.

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

Shielded Coaxial Optrode Arrays for Neurophysiology

PubMed Central

Naughton, Jeffrey R.; Connolly, Timothy; Varela, Juan A.; Lundberg, Jaclyn; Burns, Michael J.; Chiles, Thomas C.; Christianson, John P.; Naughton, Michael J.

2016-01-01

Recent progress in the study of the brain has been greatly facilitated by the development of new tools capable of minimally-invasive, robust coupling to neuronal assemblies. Two prominent examples are the microelectrode array (MEA), which enables electrical signals from large numbers of neurons to be detected and spatiotemporally correlated, and optogenetics, which enables the electrical activity of cells to be controlled with light. In the former case, high spatial density is desirable but, as electrode arrays evolve toward higher density and thus smaller pitch, electrical crosstalk increases. In the latter, finer control over light input is desirable, to enable improved studies of neuroelectronic pathways emanating from specific cell stimulation. Here, we introduce a coaxial electrode architecture that is uniquely suited to address these issues, as it can simultaneously be utilized as an optical waveguide and a shielded electrode in dense arrays. Using optogenetically-transfected cells on a coaxial MEA, we demonstrate the utility of the architecture by recording cellular currents evoked from optical stimulation. We also show the capability for network recording by radiating an area of seven individually-addressed coaxial electrode regions with cultured cells covering a section of the extent. PMID:27375415

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

Active Microelectronic Neurosensor Arrays for Implantable Brain Communication Interfaces

PubMed Central

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

2010-01-01

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

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.

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.

Multisite two-photon imaging of neurons on multielectrode arrays

NASA Astrophysics Data System (ADS)

Potter, Steve M.; Lukina, Natalia; Longmuir, Kenneth J.; Wu, Yan

2001-04-01

We wish to understand how neural systems store, recall, and process information. We are using cultured networks of cortical neurons grown on microelectrode arrays as a model system for studying the emergent properties of ensembles of living neurons. We have developed a 2-way communication interface between the cultured network and a computer- generated animal, the Neurally Controlled Animat. Neural activity is used to control the behavior of the Animat, and 2- photon time-lapse imaging is carried out in order to observe the morphological changes that might underlie changes in neural processing. The 2-photon microscope is ideal for repeated imaging over hours or days, with submicron resolution and little photodamage. We have designed a computer-controlled microscope stage that allows imaging several locations in sequence, in order to collect more image data. For the latest progress, see: http://www.caltech.edu/~pinelab/PotterGroup.htm.

C-MEMS for bio-sensing applications

NASA Astrophysics Data System (ADS)

Song, Yin; Agrawal, Richa; Wang, Chunlei

2015-05-01

Developing highly sensitive, selective, and reproducible miniaturized bio-sensing platforms require reliable biointerface which should be compatible with microfabrication techniques. In this study, we have fabricated pyrolyzed carbon arrays with high surface area as a bio-sensing electrode, and developed the surface functionalization methods to increase biomolecules immobilization efficiency and further understand electrochemical phenomena at biointerfaces. The carbon microelectrode arrays with high aspect ratio have been fabricated by carbon microelectromechanical systems (C-MEMS) and nanomaterials such as graphene have been integrated to further increase surface area. To achieve the efficient covalent immobilization of biomolecules, various oxidation and reduction functionalization methods have been investigated. The oxidation treatment in this study includes vacuum ultraviolet, electrochemical activation, UV/Ozone and oxygen RIE. The reduction treatment includes direct amination and diazonium grafting. The developed bio-sensing platform was then applied for several applications, such as: DNA sensor; H2O2 sensor; aptamer sensor and HIV sensor.

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.

Enhanced sub-micron colloidal particle separation with interdigitated microelectrode arrays using mixed AC/DC dielectrophoretic scheme.

PubMed

Swaminathan, Vikhram V; Shannon, Mark A; Bashir, Rashid

2015-04-01

Dielectrophoretic separation of particles finds a variety of applications in the capture of species such as cells, viruses, proteins, DNA from biological systems, as well as other organic and inorganic contaminants from water. The ability to capture particles is constrained by poor volumetric scaling of separation force with respect to particle diameter, as well as the weak penetration of electric fields in the media. In order to improve the separation of sub-micron colloids, we present a scheme based on multiple interdigitated electrode arrays under mixed AC/DC bias. The use of high frequency longitudinal AC bias breaks the shielding effects through electroosmotic micromixing to enhance electric fields through the electrolyte, while a transverse DC bias between the electrode arrays enables penetration of the separation force to capture particles from the bulk of the microchannel. We determine the favorable biasing conditions for field enhancement with the help of analytical models, and experimentally demonstrate the improved capture from sub-micron colloidal suspensions with the mixed AC/DC electrostatic excitation scheme over conventional AC-DEP methods.

All Inkjet-Printed Amperometric Multiplexed Biosensors Based on Nanostructured Conductive Hydrogel Electrodes.

PubMed

Li, Lanlan; Pan, Lijia; Ma, Zhong; Yan, Ke; Cheng, Wen; Shi, Yi; Yu, Guihua

2018-06-13

Multiplexing, one of the main trends in biosensors, aims to detect several analytes simultaneously by integrating miniature sensors on a chip. However, precisely depositing electrode materials and selective enzymes on distinct microelectrode arrays remains an obstacle to massively produced multiplexed sensors. Here, we report on a "drop-on-demand" inkjet printing process to fabricate multiplexed biosensors based on nanostructured conductive hydrogels in which the electrode material and several kinds of enzymes were printed on the electrode arrays one by one by employing a multinozzle inkjet system. The whole inkjet printing process can be finished within three rounds of printing and only one round of alignment. For a page of sensor arrays containing 96 working electrodes, the printing process took merely ∼5 min. The multiplexed assays can detect glucose, lactate, and triglycerides in real time with good selectivity and high sensitivity, and the results in phosphate buffer solutions and calibration serum samples are comparable. The inkjet printing process exhibited advantages of high efficiency and accuracy, which opens substantial possibilities for massive fabrication of integrated multiplexed biosensors for human health monitoring.

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.

Localized electrical stimulation of in vitro neurons using an array of sub-cellular sized electrodes.

PubMed

Braeken, Dries; Huys, Roeland; Loo, Josine; Bartic, Carmen; Borghs, Gustaaf; Callewaert, Geert; Eberle, Wolfgang

2010-12-15

The investigation of single-neuron parameters is of great interest because many aspects in the behavior and communication of neuronal networks still remain unidentified. However, the present available techniques for single-cell measurements are slow and do not allow for a high-throughput approach. We present here a CMOS compatible microelectrode array with 84 electrodes (with diameters ranging from 1.2 to 4.2 μm) that are smaller than the size of cell, thereby supporting single-cell addressability. We show controllable electroporation of a single cell by an underlying electrode while monitoring changes in the intracellular membrane potential. Further, by applying a localized electrical field between two electrodes close to a neuron while recording changes in the intracellular calcium concentration, we demonstrate activation of a single cell (∼270%, DF/F(0)), followed by a network response of the neighboring cells. The technology can be easily scaled up to larger electrode arrays (theoretically up to 137,000 electrodes/mm(2)) with active CMOS electronics integration able to perform high-throughput measurements on single cells. Copyright © 2010 Elsevier B.V. All rights reserved.

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

Microfabricated Collector-Generator Electrode Sensor for Measuring Absolute pH and Oxygen Concentrations.

PubMed

Dengler, Adam K; Wightman, R Mark; McCarty, Gregory S

2015-10-20

Fast-scan cyclic voltammetry (FSCV) has attracted attention for studying in vivo neurotransmission due to its subsecond temporal resolution, selectivity, and sensitivity. Traditional FSCV measurements use background subtraction to isolate changes in the local electrochemical environment, providing detailed information on fluctuations in the concentration of electroactive species. This background subtraction removes information about constant or slowly changing concentrations. However, determination of background concentrations is still important for understanding functioning brain tissue. For example, neural activity is known to consume oxygen and produce carbon dioxide which affects local levels of oxygen and pH. Here, we present a microfabricated microelectrode array which uses FSCV to detect the absolute levels of oxygen and pH in vitro. The sensor is a collector-generator electrode array with carbon microelectrodes spaced 5 μm apart. In this work, a periodic potential step is applied at the generator producing transient local changes in the electrochemical environment. The collector electrode continuously performs FSCV enabling these induced changes in concentration to be recorded with the sensitivity and selectivity of FSCV. A negative potential step applied at the generator produces a transient local pH shift at the collector. The generator-induced pH signal is detected using FSCV at the collector and correlated to absolute solution pH by postcalibration of the anodic peak position. In addition, in oxygenated solutions a negative potential step at the generator produces hydrogen peroxide by reducing oxygen. Hydrogen peroxide is detected with FSCV at the collector electrode, and the magnitude of the oxidative peak is proportional to absolute oxygen concentrations. Oxygen interference on the pH signal is minimal and can be accounted for with a postcalibration.

Nanoparticles Induce Changes of the Electrical Activity of Neuronal Networks on Microelectrode Array Neurochips

PubMed Central

Gramowski, Alexandra; Flossdorf, Juliane; Bhattacharya, Kunal; Jonas, Ludwig; Lantow, Margareta; Rahman, Qamar; Schiffmann, Dietmar; Weiss, Dieter G.; Dopp, Elke

2010-01-01

Background Nanomaterials are extensively used in industry and daily life, but little is known about possible health effects. An intensified research regarding toxicity of nanomaterials is urgently needed. Several studies have demonstrated that nanoparticles (NPs; diameter < 100 nm) can be transported to the central nervous system; however, interference of NPs with the electrical activity of neurons has not yet been shown. Objectives/methods We investigated the acute electrophysiological effects of carbon black (CB), hematite (Fe2O3), and titanium dioxide (TiO2) NPs in primary murine cortical networks on microelectrode array (MEA) neurochips. Uptake of NPs was studied by transmission electron microscopy (TEM), and intracellular formation of reactive oxygen species (ROS) was studied by flow cytometry. Results The multiparametric assessment of electrical activity changes caused by the NPs revealed an NP-specific and concentration-dependent inhibition of the firing patterns. The number of action potentials and the frequency of their patterns (spike and burst rates) showed a significant particle-dependent decrease and significant differences in potency. Further, we detected the uptake of CB, Fe2O3, and TiO2 into glial cells and neurons by TEM. Additionally, 24 hr exposure to TiO2 NPs caused intracellular formation of ROS in neuronal and glial cells, whereas exposure to CB and Fe2O3 NPs up to a concentration of 10 μg/cm2 did not induce significant changes in free radical levels. Conclusion NPs at low particle concentrations are able to exhibit a neurotoxic effect by disturbing the electrical activity of neuronal networks, but the underlying mechanisms depend on the particle type. PMID:20457553

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

Screening drug-induced arrhythmia [corrected] using human induced pluripotent stem cell-derived cardiomyocytes and low-impedance microelectrode arrays.

PubMed

Navarrete, Enrique G; Liang, Ping; Lan, Feng; Sanchez-Freire, Verónica; Simmons, Chelsey; Gong, Tingyu; Sharma, Arun; Burridge, Paul W; Patlolla, Bhagat; Lee, Andrew S; Wu, Haodi; Beygui, Ramin E; Wu, Sean M; Robbins, Robert C; Bers, Donald M; Wu, Joseph C

2013-09-10

Drug-induced arrhythmia is one of the most common causes of drug development failure and withdrawal from market. This study tested whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) combined with a low-impedance microelectrode array (MEA) system could improve on industry-standard preclinical cardiotoxicity screening methods, identify the effects of well-characterized drugs, and elucidate underlying risk factors for drug-induced arrhythmia. hiPSC-CMs may be advantageous over immortalized cell lines because they possess similar functional characteristics as primary human cardiomyocytes and can be generated in unlimited quantities. Pharmacological responses of beating embryoid bodies exposed to a comprehensive panel of drugs at 65 to 95 days postinduction were determined. Responses of hiPSC-CMs to drugs were qualitatively and quantitatively consistent with the reported drug effects in literature. Torsadogenic hERG blockers, such as sotalol and quinidine, produced statistically and physiologically significant effects, consistent with patch-clamp studies, on human embryonic stem cell-derived cardiomyocytes hESC-CMs. False-negative and false-positive hERG blockers were identified accurately. Consistent with published studies using animal models, early afterdepolarizations and ectopic beats were observed in 33% and 40% of embryoid bodies treated with sotalol and quinidine, respectively, compared with negligible early afterdepolarizations and ectopic beats in untreated controls. We found that drug-induced arrhythmias can be recapitulated in hiPSC-CMs and documented with low impedance MEA. Our data indicate that the MEA/hiPSC-CM assay is a sensitive, robust, and efficient platform for testing drug effectiveness and for arrhythmia screening. This system may hold great potential for reducing drug development costs and may provide significant advantages over current industry standard assays that use immortalized cell lines or animal models.

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.

Comparison of NMDA and AMPA Channel Expression and Function between Embryonic and Adult Neurons Utilizing Microelectrode Array Systems.

PubMed

Edwards, Darin; Sommerhage, Frank; Berry, Bonnie; Nummer, Hanna; Raquet, Martina; Clymer, Brad; Stancescu, Maria; Hickman, James J

2017-12-11

Microelectrode arrays (MEAs) are innovative tools used to perform electrophysiological experiments for the study of electrical activity and connectivity in populations of neurons from dissociated cultures. Reliance upon neurons derived from embryonic tissue is a common limitation of neuronal/MEA hybrid systems and perhaps of neuroscience research in general, and the use of adult neurons could model fully functional in vivo parameters more closely. Spontaneous network activity was concurrently recorded from both embryonic and adult rat neurons cultured on MEAs for up to 10 weeks in vitro to characterize the synaptic connections between cell types. The cultures were exposed to synaptic transmission antagonists against NMDA and AMPA channels, which revealed significantly different receptor profiles of adult and embryonic networks in vitro. In addition, both embryonic and adult neurons were evaluated for NMDA and AMPA channel subunit expression over five weeks in vitro. The results established that neurons derived from embryonic tissue did not express mature synaptic channels for several weeks in vitro under defined conditions. Consequently, the embryonic response to synaptic antagonists was significantly different than that of neurons derived from adult tissue sources. These results are especially significant because most studies reported with embryonic hippocampal neurons do not begin at two to four weeks in culture. In addition, the utilization of MEAs in lieu of patch-clamp electrophysiology avoided a large-scale, labor-intensive study. These results establish the utility of this unique hybrid system derived from adult hippocampal tissue in combination with MEAs and offer a more appropriate representation of in vivo function for drug discovery. It has application for neuronal development and regeneration as well as for investigations into neurodegenerative disease, traumatic brain injury, and stroke.

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.

Cross-Site Reliability of Human Induced Pluripotent Stem-Cell Derived Cardiomyocyte Based Safety Assays using Microelectrode Arrays: Results from a Blinded CiPA Pilot Study.

PubMed

Millard, Daniel; Dang, Qianyu; Shi, Hong; Zhang, Xiaou; Strock, Chris; Kraushaar, Udo; Zeng, Haoyu; Levesque, Paul; Lu, Hua-Rong; Guillon, Jean-Michel; Wu, Joseph C; Li, Yingxin; Luerman, Greg; Anson, Blake; Guo, Liang; Clements, Mike; Abassi, Yama A; Ross, James; Pierson, Jennifer; Gintant, Gary

2018-04-27

Recent in vitro cardiac safety studies demonstrate the ability of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to detect electrophysiologic effects of drugs. However, variability contributed by unique approaches, procedures, cell lines and reagents across laboratories makes comparisons of results difficult, leading to uncertainty about the role of hiPSC-CMs in defining proarrhythmic risk in drug discovery and regulatory submissions. A blinded pilot study was conducted to evaluate the electrophysiologic effects of eight well-characterized drugs on four cardiomyocyte lines using a standardized protocol across three microelectrode array (MEA) platforms (18 individual studies). Drugs were selected to define assay sensitivity of prominent repolarizing currents (E-4031 for IKr, JNJ303 for IKs) and depolarizing currents (nifedipine for ICaL, mexiletine for INa) as well as drugs affecting multi-channel block (flecainide, moxifloxacin, quinidine, and ranolazine). Inclusion criteria for final analysis was based on demonstrated sensitivity to IKr block (20% prolongation with E-4031) and L-type calcium current block (20% shortening with nifedipine). Despite differences in baseline characteristics across cardiomyocyte lines, multiple sites and instrument platforms, 10 of 18 studies demonstrated adequate sensitivity to IKr block with E-4031 and ICaL block with nifedipine for inclusion in the final analysis. Concentration-dependent effects on repolarization were observed with this qualified dataset consistent with known ionic mechanisms of single and multi-channel blocking drugs. hiPSC-CMs can detect repolarization effects elicited by single and multi-channel blocking drugs after defining pharmacologic sensitivity to IKr and ICaL block, supporting further validation efforts using hiPSC-CMs for cardiac safety studies.

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.

Cortical activation following chronic passive implantation of a wide-field suprachoroidal retinal prosthesis

NASA Astrophysics Data System (ADS)

Villalobos, Joel; Fallon, James B.; Nayagam, David A. X.; Shivdasani, Mohit N.; Luu, Chi D.; Allen, Penelope J.; Shepherd, Robert K.; Williams, Chris E.

2014-08-01

Objective. The research goal is to develop a wide-field retinal stimulating array for prosthetic vision. This study aimed at evaluating the efficacy of a suprachoroidal electrode array in evoking visual cortex activity after long term implantation. Approach. A planar silicone based electrode array (8 mm × 19 mm) was implanted into the suprachoroidal space in cats (ntotal = 10). It consisted of 20 platinum stimulating electrodes (600 μm diameter) and a trans-scleral cable terminated in a subcutaneous connector. Three months after implantation (nchronic = 6), or immediately after implantation (nacute = 4), an electrophysiological study was performed. Electrode total impedance was measured from voltage transients using 500 μs, 1 mA pulses. Electrically evoked potentials (EEPs) and multi-unit activity were recorded from the visual cortex in response to monopolar retinal stimulation. Dynamic range and cortical activation spread were calculated from the multi-unit recordings. Main results. The mean electrode total impedance in vivo following 3 months was 12.5 ± 0.3 kΩ. EEPs were recorded for 98% of the electrodes. The median evoked potential threshold was 150 nC (charge density 53 μC cm-2). The lowest stimulation thresholds were found proximal to the area centralis. Mean thresholds from multiunit activity were lower for chronic (181 ± 14 nC) compared to acute (322 ± 20 nC) electrodes (P < 0.001), but there was no difference in dynamic range or cortical activation spread. Significance. Suprachoroidal stimulation threshold was lower in chronic than acute implantation and was within safe charge limits for platinum. Electrode-tissue impedance following chronic implantation was higher, indicating the need for sufficient compliance voltage (e.g. 12.8 V for mean impedance, threshold and dynamic range). The wide-field suprachoroidal array reliably activated the retina after chronic implantation.

Lectin array and glycogene expression analyses of ovarian cancer cell line A2780 and its cisplatin-resistant derivate cell line A2780-cp.

PubMed

Zhao, Ran; Qin, Wenjun; Qin, Ruihuan; Han, Jing; Li, Can; Wang, Yisheng; Xu, Congjian

2017-01-01

Ovarian cancer is one of the most lethal gynecological malignancies, in which platinum resistance is a common cause of its relapse and death. Glycosylation has been reported to be involved in drug resistance, and glycomic analyses of ovarian cancer may improve our understanding of the mechanisms underlying cancer cell drug resistance and provide potential biomarkers and therapeutic targets. The serous ovarian cancer cell line A2780 and its platinum-resistant counterpart A2780-cp were used in this study. We performed a lectin array analysis to compare the glycosylation patterns of the two cell lines, a gene expression array was employed to probe the differences in glycogenes. Furthermore, the results were verified by lectin blots. A2780-cp cell exhibited stronger intensities of Lens culinaris (LCA) Canavalia ensiformis (ConA), and Lycopersicon esculentum (LEL) and weaker intensities of Sambucus nigra (SNA) lectins. The gene expression array analysis revealed increased expression of Fut8, B3gnt4, B3gnt5, B4galt2 and decreased expression of Fut1 and ST6GalNAc 6 expression were evident in the A2780-cp cells. The lectin blot confirmed the differences in LCA, ConA, SNA and LEL between the A2780 and A2780-cp cells. The combination of the lectin and gene expression analyses showed that the levels of core fucosylation and poly-LacNAc were increased in the A2780-cp cells and the levels of Fuc α1-2(gal β1-4) GlcNAc and α2-6-linked sialic structures were decreased in the A2780-cp cells. These glycans represent potential biomarkers and might be involved in the mechanism of drug resistance in ovarian cancer.

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

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

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

Electronic desalting for controlling the ionic environment in droplet-based biosensing platforms

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

Swaminathan, Vikhram Vilasur; Dak, Piyush; Alam, Muhammad A., E-mail: rbashir@illinois.edu, E-mail: alam@purdue.edu

2015-02-02

The ability to control the ionic environment in saline waters and aqueous electrolytes is useful for desalination as well as electronic biosensing. We demonstrate a method of electronic desalting at micro-scale through on-chip micro electrodes. We show that, while desalting is limited in bulk solutions with unlimited availability of salts, significant desalting of ≥1 mM solutions can be achieved in sub-nanoliter volume droplets with diameters of ∼250 μm. Within these droplets, by using platinum-black microelectrodes and electrochemical surface treatments, we can enhance the electrode surface area to achieve >99% and 41% salt removal in 1 mM and 10 mM salt concentrations, respectively. Through self-consistentmore » simulations and experimental measurements, we demonstrate that conventional double-layer theory over-predicts the desalting capacity and, hence, cannot be used to model systems that are mass limited or undergoing significant salt removal from the bulk. Our results will provide a better understanding of capacitive desalination, as well as a method for salt manipulation in high-throughput droplet-based microfluidic sensing platforms.« less

Iridium oxide pH sensor for biomedical applications. Case urea-urease in real urine samples.

PubMed

Prats-Alfonso, Elisabet; Abad, Llibertat; Casañ-Pastor, Nieves; Gonzalo-Ruiz, Javier; Baldrich, Eva

2013-01-15

This work demonstrates the implementation of iridium oxide films (IROF) grown on silicon-based thin-film platinum microelectrodes, their utilization as a pH sensor, and their successful formatting into a urea pH sensor. In this context, Pt electrodes were fabricated on Silicon by using standard photolithography and lift-off procedures and IROF thin films were growth by a dynamic oxidation electrodeposition method (AEIROF). The AEIROF pH sensor reported showed a super-Nerstian (72.9±0.9mV/pH) response between pH 3 and 11, with residual standard deviation of both repeatability and reproducibility below 5%, and resolution of 0.03 pH units. For their application as urea pH sensors, AEIROF electrodes were reversibly modified with urease-coated magnetic microparticles (MP) using a magnet. The urea pH sensor provided fast detection of urea between 78μM and 20mM in saline solution, in sample volumes of just 50μL. The applicability to urea determination in real urine samples is discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Electronic desalting for controlling the ionic environment in droplet-based biosensing platforms

NASA Astrophysics Data System (ADS)

Swaminathan, Vikhram Vilasur; Dak, Piyush; Reddy, Bobby; Salm, Eric; Duarte-Guevara, Carlos; Zhong, Yu; Fischer, Andrew; Liu, Yi-Shao; Alam, Muhammad A.; Bashir, Rashid

2015-02-01

The ability to control the ionic environment in saline waters and aqueous electrolytes is useful for desalination as well as electronic biosensing. We demonstrate a method of electronic desalting at micro-scale through on-chip micro electrodes. We show that, while desalting is limited in bulk solutions with unlimited availability of salts, significant desalting of ≥1 mM solutions can be achieved in sub-nanoliter volume droplets with diameters of ˜250 μm. Within these droplets, by using platinum-black microelectrodes and electrochemical surface treatments, we can enhance the electrode surface area to achieve >99% and 41% salt removal in 1 mM and 10 mM salt concentrations, respectively. Through self-consistent simulations and experimental measurements, we demonstrate that conventional double-layer theory over-predicts the desalting capacity and, hence, cannot be used to model systems that are mass limited or undergoing significant salt removal from the bulk. Our results will provide a better understanding of capacitive desalination, as well as a method for salt manipulation in high-throughput droplet-based microfluidic sensing platforms.

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.

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

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.

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

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.

Galvanic Couple Current and Potential Distribution between a Mg Electrode and 2024-T351 under Droplets Analyzed by Microelectrode Arrays

DTIC Science & Technology

2015-11-04

cathodically to – 1.5 V vs. SCE in aearated NaCl solution dissolves at a rate as high as 4 mA/cm2. However, the same alloy was shown to avoid significant...MgRP coating could be utilized in place of the Mg electrode. It is well known that the wettability of the surface of aluminum and its oxides is high ...aluminum alloys , such as precipitation age hardened 2024-T351, and has performed well in field studies.1–13 The MgRP is designed to be applied to an

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

NASA Astrophysics Data System (ADS)

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

2005-03-01

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

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.

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

Impedance biosensor based on interdigitated electrode array for detection of E.coli O157:H7 in food products

NASA Astrophysics Data System (ADS)

Ghosh Dastider, Shibajyoti; Barizuddin, Syed; Dweik, Majed; Almasri, Mahmoud F.

2012-05-01

An impedance biosensor was designed, fabricated and tested for detection of viable Escherichia coli O157:H7 in food samples. This device consists of interdigitated microelectrode array (IDEA) fabricated using thin layer of sputtered gold, embedded under a polydimethylsiloxane (PDMS) microchannel. The array of electrodes is designed to detect viable EColi in different food products. The active surface area of the detection array was modified using goat anti-E.coli polyclonal IgG antibody. Contaminated food samples were tested by infusing the supernatant containing bacteria over the IDEA's, through the microchannel. Antibody-antigen binding on the electrodes results in impedance change. Four serial concentrations of E.coli contaminated food samples (3x102 CFUmL-1 to 3x105 CFUmL-1) were tested. The biosensor successfully detected the E.coli samples, with the lower detection limit being 3x103 CFUmL-1 (up to 3cells/μl). Comparing the test results with an IDEA impedance biosensor without microchannel (published elsewhere) indicates that this biosensor have two order of magnitude times higher sensitivity. The proposed biosensor provides qualitative and quantitative detection, and potentially could be used for detection of other type of bacteria by immobilizing the specific type of antibody.

Spatial changes in acid secretion from isolated stomach tissue using a pH-histamine sensing microarray.

PubMed

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

2010-03-01

The acid secretion mechanism can be studied by measuring a series of metabolic markers and neurotransmitters from in vitro isolated tissue. A microelectrode array was used to monitor proton concentration and histamine levels from isolated guinea pig stomach tissue. The device was partially modified using iridium oxide to form a series of pH sensors, whereas unmodified gold microelectrodes were used to measure the level of histamine in the gut. Real-time measurements in the presence of the H2-receptor antagonist ranitidine produced significant decreases in the overall Delta pH response, as expected. Also, a significant variation in the Delta pH response in between pH sensors was observed in the presence of pharmacological treatment due to structural features of the tissue. No significant differences in Delta i(H) were detected in the presence of ranitidine as expected. More significantly, clear variations in Delta pH responses between animals in control conditions and those in the presence of ranitidine was observed highlighting possible variation in parietal cell density and/or variations in tissue activity. These results identify great possibilities in applying these multi-sensing devices as a long-term stable personalised diagnostic tool for pharmacological screening and disease status.

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

Glutathione S-transferase P1 (GSTP1) directly influences platinum drug chemosensitivity in ovarian tumour cell lines.

PubMed

Sawers, L; Ferguson, M J; Ihrig, B R; Young, H C; Chakravarty, P; Wolf, C R; Smith, G

2014-09-09

Chemotherapy response in ovarian cancer patients is frequently compromised by drug resistance, possibly due to altered drug metabolism. Platinum drugs are metabolised by glutathione S-transferase P1 (GSTP1), which is abundantly, but variably expressed in ovarian tumours. We have created novel ovarian tumour cell line models to investigate the extent to which differential GSTP1 expression influences chemosensitivity. Glutathione S-transferase P1 was stably deleted in A2780 and expression significantly reduced in cisplatin-resistant A2780DPP cells using Mission shRNA constructs, and MTT assays used to compare chemosensitivity to chemotherapy drugs used to treat ovarian cancer. Differentially expressed genes in GSTP1 knockdown cells were identified by Illumina HT-12 expression arrays and qRT-PCR analysis, and altered pathways predicted by MetaCore (GeneGo) analysis. Cell cycle changes were assessed by FACS analysis of PI-labelled cells and invasion and migration compared in quantitative Boyden chamber-based assays. Glutathione S-transferase P1 knockdown selectively influenced cisplatin and carboplatin chemosensitivity (2.3- and 4.83-fold change in IC50, respectively). Cell cycle progression was unaffected, but cell invasion and migration was significantly reduced. We identified several novel GSTP1 target genes and candidate platinum chemotherapy response biomarkers. Glutathione S-transferase P1 has an important role in cisplatin and carboplatin metabolism in ovarian cancer cells. Inter-tumour differences in GSTP1 expression may therefore influence response to platinum-based chemotherapy in ovarian cancer patients.

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

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

PubMed

Massobrio, Giuseppe; Martinoia, Sergio; Massobrio, Paolo

2018-02-01

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

Development of micro-electromechanical system (MEMS) cochlear biomodel

NASA Astrophysics Data System (ADS)

Ngelayang, Thailis Bounya Anak; Latif, Rhonira

2015-05-01

Human cochlear is undeniably one of the most amazing organs in human body. The functional mechanism is very unique in terms of its ability to convert the sound waves in the form of mechanical vibrations into the electrical nerve impulses. It is known that the normal human auditory system can perceive the audible frequency range between 20 Hz to 20 kHz. Scientists have conducted several researches trying to build the artificial basilar membrane in the human cochlea (cochlear biomodel). Micro-electromechanical system (MEMS) is one of the potential inventions that have the ability to mimic the active behavior of the basilar membrane. In this paper, an array of MEMS bridge beams that are mechanically sensitive to the perceived audible frequency has been proposed. An array of bridge bridge beams with 0.5 µm thickness and length varying from 200 µm to 2000 µm have been designed operate within the audible frequency range. In the bridge beams design, aluminium (Al), copper (Cu), tantalum (Ta) and platinum (Pt) have considered as the material for the bridge beam structure. From the finite element (FE) and lumped element (LE) models of the MEMS bridge beams, platinum has been found to be the best material for the cochlear biomodel design, closely mimicking the basilar membrane.

Development of micro-electromechanical system (MEMS) cochlear biomodel

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

Ngelayang, Thailis Bounya Anak; Latif, Rhonira

Human cochlear is undeniably one of the most amazing organs in human body. The functional mechanism is very unique in terms of its ability to convert the sound waves in the form of mechanical vibrations into the electrical nerve impulses. It is known that the normal human auditory system can perceive the audible frequency range between 20 Hz to 20 kHz. Scientists have conducted several researches trying to build the artificial basilar membrane in the human cochlea (cochlear biomodel). Micro-electromechanical system (MEMS) is one of the potential inventions that have the ability to mimic the active behavior of the basilar membrane. Inmore » this paper, an array of MEMS bridge beams that are mechanically sensitive to the perceived audible frequency has been proposed. An array of bridge bridge beams with 0.5 µm thickness and length varying from 200 µm to 2000 µm have been designed operate within the audible frequency range. In the bridge beams design, aluminium (Al), copper (Cu), tantalum (Ta) and platinum (Pt) have considered as the material for the bridge beam structure. From the finite element (FE) and lumped element (LE) models of the MEMS bridge beams, platinum has been found to be the best material for the cochlear biomodel design, closely mimicking the basilar membrane.« less

Genomic analysis of genetic heterogeneity and evolution in high-grade serous ovarian carcinoma

PubMed Central

Cooke, Susanna L; Ng, Charlotte KY; Melnyk, Nataliya; Garcia, Maria J; Hardcastle, Tom; Temple, Jillian; Langdon, Simon; Huntsman, David; Brenton, James D

2010-01-01

Resistance to chemotherapy in ovarian cancer is poorly understood. Evolutionary models of cancer predict that, following treatment, resistance emerges either due to outgrowth of an intrinsically resistant sub-clone, or evolves in residual disease under the selective pressure of treatment. To investigate genetic evolution in high-grade serous (HGS) ovarian cancers we first analysed cell line series derived from three cases of HGS carcinoma before and after platinum resistance had developed (PEO1, PEO4 and PEO6, PEA1 and PEA2, and PEO14 and PEO23). Analysis with 24-colour fluorescence in situ hybridisation and SNP array comparative genomic hybridisation (CGH) showed mutually exclusive endoreduplication and loss of heterozygosity events in clones present at different timepoints in the same individual. This implies that platinum sensitive and resistant disease was not linearly related but shared a common ancestor at an early stage of tumour development. Array CGH analysis of six paired pre- and post-neoadjuvant treatment HGS samples from the CTCR-OV01 clinical study did not show extensive copy number differences, suggesting that one clone was strongly dominant at presentation. These data show that cisplatin resistance in HGS carcinoma develops from pre-existing minor clones but that enrichment for these clones is not apparent during short-term chemotherapy treatment. PMID:20581869

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.

Array-type NH.sub.3 sensor

DOEpatents

West, David Lawrence; Montgomery, Frederick Charles; Armstrong, Timothy R; Warmack, Robert J

2013-12-31

An array-type sensor that senses NH.sub.3 includes non-Nernstian sensing elements constructed from metal and/or metal-oxide electrodes on an O.sub.2 ion conducting substrate. In one example sensor, one electrode may be made of platinum, another electrode may be made of manganese (III) oxide (Mn.sub.2O.sub.3), and another electrode may be made of tungsten trioxide (WO.sub.3). Some sensing elements may further include an electrode made of La.sub.0.6Sr.sub.0.4Co.sub.0.2Fe.sub0.8O.sub.3 and another electrode made of LaCr.sub.0.95.Mg.sub.0.05O.sub.3.

A CMOS active pixel sensor for retinal stimulation

NASA Astrophysics Data System (ADS)

Prydderch, Mark L.; French, Marcus J.; Mathieson, Keith; Adams, Christopher; Gunning, Deborah; Laudanski, Jonathan; Morrison, James D.; Moodie, Alan R.; Sinclair, James

2006-02-01

Degenerative photoreceptor diseases, such as age-related macular degeneration and retinitis pigmentosa, are the most common causes of blindness in the western world. A potential cure is to use a microelectronic retinal prosthesis to provide electrical stimulation to the remaining healthy retinal cells. We describe a prototype CMOS Active Pixel Sensor capable of detecting a visual scene and translating it into a train of electrical pulses for stimulation of the retina. The sensor consists of a 10 x 10 array of 100 micron square pixels fabricated on a 0.35 micron CMOS process. Light incident upon each pixel is converted into output current pulse trains with a frequency related to the light intensity. These outputs are connected to a biocompatible microelectrode array for contact to the retinal cells. The flexible design allows experimentation with signal amplitudes and frequencies in order to determine the most appropriate stimulus for the retina. Neural processing in the retina can be studied by using the sensor in conjunction with a Field Programmable Gate Array (FPGA) programmed to behave as a neural network. The sensor has been integrated into a test system designed for studying retinal response. We present the most recent results obtained from this sensor.

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

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

PubMed Central

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

2015-01-01

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

Multichannel Boron Doped Nanocrystalline Diamond Ultramicroelectrode Arrays: Design, Fabrication and Characterization

PubMed Central

Kiran, Raphael; Rousseau, Lionel; Lissorgues, Gaëlle; Scorsone, Emmanuel; Bongrain, Alexandre; Yvert, Blaise; Picaud, Serge; Mailley, Pascal; Bergonzo, Philippe

2012-01-01

We report on the fabrication and characterization of an 8 × 8 multichannel Boron Doped Diamond (BDD) ultramicro-electrode array (UMEA). The device combines both the assets of microelectrodes, resulting from conditions in mass transport from the bulk solution toward the electrode, and of BDD's remarkable intrinsic electrochemical properties. The UMEAs were fabricated using an original approach relying on the selective growth of diamond over pre-processed 4 inches silicon substrates. The prepared UMEAs were characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The results demonstrated that the electrodes have exhibited a very fast electrode transfer rate (k0) up to 0.05 cm·s−1 (in a fast redox couple) and on average, a steady state limiting current (in a 0.5 M potassium chloride aqueous solution containing 1 mM Fe(CN)64− ion at 100 mV·s−1) of 1.8 nA. The UMEAs are targeted for electrophysiological as well as analytical applications. PMID:22969367

Review on thin-film transistor technology, its applications, and possible new applications to biological cells

NASA Astrophysics Data System (ADS)

Tixier-Mita, Agnès; Ihida, Satoshi; Ségard, Bertrand-David; Cathcart, Grant A.; Takahashi, Takuya; Fujita, Hiroyuki; Toshiyoshi, Hiroshi

2016-04-01

This paper presents a review on state-of-the-art of thin-film transistor (TFT) technology and its wide range of applications, not only in liquid crystal displays (TFT-LCDs), but also in sensing devices. The history of the evolution of the technology is first given. Then the standard applications of TFT-LCDs, and X-ray detectors, followed by state-of-the-art applications in the field of chemical and biochemical sensing are presented. TFT technology allows the fabrication of dense arrays of independent and transparent microelectrodes on large glass substrates. The potential of these devices as electrical substrates for biological cell applications is then described. The possibility of using TFT array substrates as new tools for electrical experiments on biological cells has been investigated for the first time by our group. Dielectrophoresis experiments and impedance measurements on yeast cells are presented here. Their promising results open the door towards new applications of TFT technology.

Making structures for cell engineering.

PubMed

Wilkinson, C D W

2004-10-22

This is a mainly historical account of the events, methods and artifacts arising from my collaboration with Adam Curtis over the past twenty years to make exercise grounds for biological cells. Initially the structures were made in fused silica by photo-lithography and dry etching. The need to make micron-sized features in biodegradable polymers, led to the development of embossing techniques. Some cells response to grooves only a few tens of nanometers deep--this led to a desire to find the response of cells to features of nanometric size overall. Regular arrays of such features were made using electron beam lithography for definition of the pattern. Improvements were made in the lithographic techniques to allow arrays to be defined over areas bigger than 1 cm2. Structures with microelectrodes arranged inside guiding grooves to allow the formation of sparse predetermined networks of neurons were made. It is concluded that the creation of pattern, as in vivo, in assemblies of regrown cells in scaffolds may well be necessary in advanced cell engineering applications.

Neuroprosthetic limb control with electrocorticography: approaches and challenges.

PubMed

Thakor, Nitish V; Fifer, Matthew S; Hotson, Guy; Benz, Heather L; Newman, Geoffrey I; Milsap, Griffin W; Crone, Nathan E

2014-01-01

Advanced upper limb prosthetics, such as the Johns Hopkins Applied Physics Lab Modular Prosthetic Limb (MPL), are now available for research and preliminary clinical applications. Research attention has shifted to developing means of controlling these prostheses. Penetrating microelectrode arrays are often used in animal and human models to decode action potentials for cortical control. These arrays may suffer signal loss over the long-term and therefore should not be the only implant type investigated for chronic BMI use. Electrocorticographic (ECoG) signals from electrodes on the cortical surface may provide more stable long-term recordings. Several studies have demonstrated ECoG's potential for decoding cortical activity. As a result, clinical studies are investigating ECoG encoding of limb movement, as well as its use for interfacing with and controlling advanced prosthetic arms. This overview presents the technical state of the art in the use of ECoG in controlling prostheses. Technical limitations of the current approach and future directions are also presented.

Metal oxide nanorod arrays on monolithic substrates

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

Gao, Pu-Xian; Guo, Yanbing; Ren, Zheng

A metal oxide nanorod array structure according to embodiments disclosed herein includes a monolithic substrate having a surface and multiple channels, an interface layer bonded to the surface of the substrate, and a metal oxide nanorod array coupled to the substrate surface via the interface layer. The metal oxide can include ceria, zinc oxide, tin oxide, alumina, zirconia, cobalt oxide, and gallium oxide. The substrate can include a glass substrate, a plastic substrate, a silicon substrate, a ceramic monolith, and a stainless steel monolith. The ceramic can include cordierite, alumina, tin oxide, and titania. The nanorod array structure can includemore » a perovskite shell, such as a lanthanum-based transition metal oxide, or a metal oxide shell, such as ceria, zinc oxide, tin oxide, alumina, zirconia, cobalt oxide, and gallium oxide, or a coating of metal particles, such as platinum, gold, palladium, rhodium, and ruthenium, over each metal oxide nanorod. Structures can be bonded to the surface of a substrate and resist erosion if exposed to high velocity flow rates.« less

Carbon nanotubes based methanol sensor for fuel cells application.

PubMed

Kim, D W; Lee, J S; Lee, G S; Overzet, L; Kozlov, M; Aliev, A E; Park, Y W; Yang, D J

2006-11-01

An electrochemical sensor is built using vertically grown multi-walled carbon nanotubes (MWNTs) micro-array to detect methanol concentration in water. This study is done for the potential use of the array as methanol sensor for portable units of direct methanol fuel cells (DMFCs). Platinum (Pt) nanoparticles electro-deposited CNTs (Pt/CNTs) electrode shows high sensitivity in the measurement of methanol concentration in water with cyclic voltammetry (CV) measurement at room temperature. Further investigation has also been undertaken to measure the concentration by changing the amount of the mixture of methanol and formic acid in water. We compared the performance of our micro array sensor built with Pt/CNTs electrodes versus that of Pt wire electrode using CV measurement. We found that our Pt/CNTs array sensor shows high sensitivity and detects methanol concentrations in the range of 0.04 M to 0.10 M. In addition, we found that co-use of formic acid as electrolyte enables us to measure up to 1.0 M methanol concentration.

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

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.

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.

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

Macrocyclic Receptor for Precious Gold, Platinum, or Palladium Coordination Complexes.

PubMed

Liu, Wenqi; Oliver, Allen G; Smith, Bradley D

2018-06-06

Two macrocyclic tetralactam receptors are shown to selectively encapsulate anionic, square-planar chloride and bromide coordination complexes of gold(III), platinum(II), and palladium(II). Both receptors have a preorganized structure that is complementary to its precious metal guest. The receptors do not directly ligate the guest metal center but instead provide an array of arene π-electron donors that interact with the electropositive metal and hydrogen-bond donors that interact with the outer electronegative ligands. This unique mode of supramolecular recognition is illustrated by six X-ray crystal structures showing receptor encapsulation of AuCl 4 - , AuBr 4 - , PtCl 4 -2 , or Pd 2 Cl 6 -2 . In organic solution, the 1:1 association constants correlate with specific supramolecular features identified in the solid state. Technical applications using these receptors are envisioned in a wide range of fields that involve precious metals, including mining, recycling, catalysis, nanoscience, and medicine.

Recent advancements in nanoelectrodes and nanopipettes used in combined scanning electrochemical microscopy techniques.

PubMed

Kranz, Christine

2014-01-21

In recent years, major developments in scanning electrochemical microscopy (SECM) have significantly broadened the application range of this electroanalytical technique from high-resolution electrochemical imaging via nanoscale probes to large scale mapping using arrays of microelectrodes. A major driving force in advancing the SECM methodology is based on developing more sophisticated probes beyond conventional micro-disc electrodes usually based on noble metals or carbon microwires. This critical review focuses on the design and development of advanced electrochemical probes particularly enabling combinations of SECM with other analytical measurement techniques to provide information beyond exclusively measuring electrochemical sample properties. Consequently, this critical review will focus on recent progress and new developments towards multifunctional imaging.

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.

Biocompatible implants and methods of making and attaching the same

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

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

2014-10-07

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

Microfluidic and Label-Free Multi-Immunosensors Based on Carbon Nanotube Microelectrodes

NASA Astrophysics Data System (ADS)

Tsujita, Yuichi; Maehashi, Kenzo; Matsumoto, Kazuhiko; Chikae, Miyuki; Takamura, Yuzuru; Tamiya, Eiichi

2009-06-01

We fabricated microfluidic and label-free multi-immunosensors by the integration of carbon nanotube (CNT)-arrayed electrodes and microchannels with pneumatic micropumps made of poly(dimethylsiloxane). In the microfluidic systems, four kinds of sample solutions were transported from each liquid inlet to microchannels using six pneumatic micropumps. As a result, two kinds of antibodies were immobilized onto different CNT electrodes using the microfluidic systems. Next, two kinds of cancer markers, prostate specific antigen and human chorionic gonadotropin in phosphate buffer solution, were simultaneously detected by differential pulse voltammetry. Therefore, microfludic multi-immunosensors based on CNT electrodes and pneumatic micropumps are useful for the development of multiplex hand-held biosensors.

Developments and Applications of Electrogenerated Chemiluminescence Sensors Based on Micro- and Nanomaterials

PubMed Central

Hazelton, Sandra G.; Zheng, Xingwang; Zhao, Julia Xiaojun; Pierce, David T.

2008-01-01

A variety of recent developments and applications of electrogenerated chemiluminescence (ECL) for sensors are described. While tris(2,2′-bipyridyl)-ruthenium(II) and luminol have dominated and continue to pervade the field of ECL-based sensors, recent work has focused on use of these lumophores with micro- and nanomaterials. It has also extended to inherently luminescent nanomaterials, such as quantum dots. Sensor configurations including microelectrode arrays and microfluidics are reviewed and, with the recent trend toward increased use of nanomaterials, special attention has been given to sensors which include thin films, nanoparticles and nanotubes. Applications of ECL labels and examples of label-free sensing that incorporate nanomaterials are also discussed. PMID:27873850

Science& Technology Review November 2003

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

McMahon, D

2003-11-01

This issue of Science & Technology Review covers the following topics: (1) We Will Always Need Basic Science--Commentary by Tomas Diaz de la Rubia; (2) When Semiconductors Go Nano--experiments and computer simulations reveal some surprising behavior of semiconductors at the nanoscale; (3) Retinal Prosthesis Provides Hope for Restoring Sight--A microelectrode array is being developed for a retinal prosthesis; (4) Maglev on the Development Track for Urban Transportation--Inductrack, a Livermore concept to levitate train cars using permanent magnets, will be demonstrated on a 120-meter-long test track; and (5) Power Plant on a Chip Moves Closer to Reality--Laboratory-designed fuel processor gives powermore » boost to dime-size fuel cell.« less

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.

The role of extracellular conductivity profiles in compartmental models for neurons: particulars for layer 5 pyramidal cells.

PubMed

Wang, Kai; Riera, Jorge; Enjieu-Kadji, Herve; Kawashima, Ryuta

2013-07-01

With the rapid increase in the number of technologies aimed at observing electric activity inside the brain, scientists have felt the urge to create proper links between intracellular- and extracellular-based experimental approaches. Biophysical models at both physical scales have been formalized under assumptions that impede the creation of such links. In this work, we address this issue by proposing a multicompartment model that allows the introduction of complex extracellular and intracellular resistivity profiles. This model accounts for the geometrical and electrotonic properties of any type of neuron through the combination of four devices: the integrator, the propagator, the 3D connector, and the collector. In particular, we applied this framework to model the tufted pyramidal cells of layer 5 (PCL5) in the neocortex. Our model was able to reproduce the decay and delay curves of backpropagating action potentials (APs) in this type of cell with better agreement with experimental data. We used the voltage drops of the extracellular resistances at each compartment to approximate the local field potentials generated by a PCL5 located in close proximity to linear microelectrode arrays. Based on the voltage drops produced by backpropagating APs, we were able to estimate the current multipolar moments generated by a PCL5. By adding external current sources in parallel to the extracellular resistances, we were able to create a sensitivity profile of PCL5 to electric current injections from nearby microelectrodes. In our model for PCL5, the kinetics and spatial profile of each ionic current were determined based on a literature survey, and the geometrical properties of these cells were evaluated experimentally. We concluded that the inclusion of the extracellular space in the compartmental models of neurons as an extra electrotonic medium is crucial for the accurate simulation of both the propagation of the electric potentials along the neuronal dendrites and the neuronal reactivity to an electrical stimulation using external microelectrodes.

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.

Intrinsic synchronization of an array of spin-torque oscillators driven by the spin-Hall effect

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

Siracusano, G., E-mail: giuliosiracusano@gmail.com; Puliafito, V.; Giordano, A.

2015-05-07

This paper micromagnetically studies the magnetization dynamics driven by the spin-Hall effect in a Platinum/Permalloy bi-layer. For a certain field and current range, the excitation of a uniform mode, characterized by a power with a spatial distribution in the whole ferromagnetic cross section, is observed. We suggest to use the ferromagnet of the bi-layer as basis for the realization of an array of spin-torque oscillators (STOs): the Permalloy ferromagnet will act as shared free layer, whereas the spacers and the polarizers are built on top of it. Following this strategy, the frequency of the uniform mode will be the samemore » for the whole device, creating an intrinsic synchronization. The synchronization of an array of parallely connected STOs will allow to increase the output power, as necessary for technological applications.« less

Hydrogen peroxide biosensor based on microperoxidase-11 immobilized in a silica cavity array electrode.

PubMed

Tian, Shu; Zhou, Qun; Gu, Zhuomin; Gu, Xuefang; Zhao, Lili; Li, Yan; Zheng, Junwei

2013-03-30

Hydrogen peroxide biosensor based on the silica cavity array modified indium-doped tin oxide (ITO) electrode was constructed. An array of silica microcavities was fabricated by electrodeposition using the assembled polystyrene particles as template. Due to the resistance gradient of the silica cavity structure, the silica cavity exhibits a confinement effect on the electrochemical reactions, making the electrode function as an array of "soft" microelectrodes. The covalently immobilized microperoxidase-11(MP-11) inside these SiO2 cavities can keep its physiological activities, the electron transfer between the MP-11 and electrode was investigated through electrochemical method. The cyclic voltammetric curve shows a quasi-reversible electrochemical redox behavior with a pair of well-defined redox peaks, the cathodic and anodic peaks are located at -0.26 and -0.15V. Furthermore, the modified electrode exhibits high electrocatalytic activity toward the reduction of hydrogen peroxide and also shows good analytical performance for the amperometric detection of H2O2 with a linear range from 2×10(-6) to 6×10(-4)M. The good reproducibility and long-term stability of this novel electrode not only offer an opportunity for the detection of H2O2 in low concentration, but also provide a platform to construct various biosensors based on many other enzymes. Copyright © 2013 Elsevier B.V. All rights reserved.

Glutathione S-transferase P1 (GSTP1) directly influences platinum drug chemosensitivity in ovarian tumour cell lines

PubMed Central

Sawers, L; Ferguson, M J; Ihrig, B R; Young, H C; Chakravarty, P; Wolf, C R; Smith, G

2014-01-01

Background: Chemotherapy response in ovarian cancer patients is frequently compromised by drug resistance, possibly due to altered drug metabolism. Platinum drugs are metabolised by glutathione S-transferase P1 (GSTP1), which is abundantly, but variably expressed in ovarian tumours. We have created novel ovarian tumour cell line models to investigate the extent to which differential GSTP1 expression influences chemosensitivity. Methods: Glutathione S-transferase P1 was stably deleted in A2780 and expression significantly reduced in cisplatin-resistant A2780DPP cells using Mission shRNA constructs, and MTT assays used to compare chemosensitivity to chemotherapy drugs used to treat ovarian cancer. Differentially expressed genes in GSTP1 knockdown cells were identified by Illumina HT-12 expression arrays and qRT–PCR analysis, and altered pathways predicted by MetaCore (GeneGo) analysis. Cell cycle changes were assessed by FACS analysis of PI-labelled cells and invasion and migration compared in quantitative Boyden chamber-based assays. Results: Glutathione S-transferase P1 knockdown selectively influenced cisplatin and carboplatin chemosensitivity (2.3- and 4.83-fold change in IC50, respectively). Cell cycle progression was unaffected, but cell invasion and migration was significantly reduced. We identified several novel GSTP1 target genes and candidate platinum chemotherapy response biomarkers. Conclusions: Glutathione S-transferase P1 has an important role in cisplatin and carboplatin metabolism in ovarian cancer cells. Inter-tumour differences in GSTP1 expression may therefore influence response to platinum-based chemotherapy in ovarian cancer patients. PMID:25010864

High energy efficiency and high power density proton exchange membrane fuel cells: Electrode kinetics and mass transport

NASA Technical Reports Server (NTRS)

Srinivasan, Supramaniam; Velev, Omourtag A.; Parthasathy, Arvind; Manko, David J.; Appleby, A. John

1991-01-01

The development of proton exchange membrane (PEM) fuel cell power plants with high energy efficiencies and high power densities is gaining momentum because of the vital need of such high levels of performance for extraterrestrial (space, underwater) and terrestrial (power source for electric vehicles) applications. Since 1987, considerable progress has been made in achieving energy efficiencies of about 60 percent at a current density of 200 mA/sq cm and high power densities (greater than 1 W/sq cm) in PEM fuel cells with high (4 mg/sq cm) or low (0.4 mg/sq cm) platinum loadings in electrodes. The following areas are discussed: (1) methods to obtain these high levels of performance with low Pt loading electrodes - by proton conductor impregnation into electrodes, localization of Pt near front surface; (2) a novel microelectrode technique which yields electrode kinetic parameters for oxygen reduction and mass transport parameters; (3) demonstration of lack of water transport from anode to cathode; (4) modeling analysis of PEM fuel cell for comparison with experimental results and predicting further improvements in performance; and (5) recommendations of needed research and development for achieving the above goals.

Microstimulation of primary afferent neurons in the L7 dorsal root ganglia using multielectrode arrays in anesthetized cats: thresholds and recruitment properties

NASA Astrophysics Data System (ADS)

Gaunt, R. A.; Hokanson, J. A.; Weber, D. J.

2009-10-01

Current research in motor neural prosthetics has focused primarily on issues related to the extraction of motor command signals from the brain (e.g. brain-machine interfaces) to direct the motion of prosthetic limbs. Patients using these types of systems could benefit from a somatosensory neural interface that conveys natural tactile and kinesthetic sensations for the prosthesis. Electrical microstimulation within the dorsal root ganglia (DRG) has been proposed as one method to accomplish this, yet little is known about the recruitment properties of electrical microstimulation in activating nerve fibers in this structure. Current-controlled microstimulation pulses in the range of 1-15 µA (200 µs, leading cathodic pulse) were delivered to the L7 DRG in four anesthetized cats using penetrating microelectrode arrays. Evoked responses and their corresponding conduction velocities (CVs) were measured in the sciatic nerve with a 5-pole nerve cuff electrode arranged as two adjacent tripoles. It was found that in 76% of the 69 electrodes tested, the stimulus threshold was less than or equal to 3 µA, with the lowest recorded threshold being 1.1 µA. The CVs of afferents recruited at threshold had a bimodal distribution with peaks at 70 m s-1 and 85 m s-1. In 53% of cases, the CV of the response at threshold was slower (i.e. smaller diameter fiber) than the CVs of responses observed at increasing stimulation amplitudes. In summary, we found that microstimulation applied through penetrating microelectrodes in the DRG provides selective recruitment of afferent fibers from a range of sensory modalities (as identified by CVs) at very low stimulation intensities. We conclude that the DRG may serve as an attractive location from which to introduce surrogate somatosensory feedback into the nervous system.

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.

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).

Nanodroplet impact onto solid platinum surface: Spreading and bouncing

NASA Astrophysics Data System (ADS)

Lussier, Daniel; Ventikos, Yiannis

2009-11-01

The impact of droplets onto solid surfaces is found in a huge variety of natural and technological applications, from rain drops splashing on the pavement, to material manufacturing by molten droplet deposition. Taking inspiration from existing microfluidic technologies (i.e. lab-on-chip), there is increasing interest in the use of nanodroplets (D < 100 nm) for a number of applications such as drug delivery and semiconductor device manufacturing. However, as the size of the droplet is reduced into the nanoscale, the direct use of previously obtained macroscopic results is not guaranteed. At the nanoscale, important effects due to the molecular nature of the fluid, thermal fluctuations and reduced dimensionality can play a critical role in determining system dynamics. In this paper we present the results of large-scale, fully atomistic, three-dimensional molecular dynamics (MD) simulation of an argon nanodroplet (D = 18 nm, 54 000 atoms) impact onto a solid platinum surface, using the LAMMPS software package. The fluid argon is modeled using the well-known Lennard-Jones (LJ) potential, while the embedded-atom model (EAM) potential is used for the solid platinum. By varying both the impact velocities (10-1000 m/s) and the wettability of the solid surface a wide range of impact behaviors is observed, from smooth spreading, to bouncing recoil, pointing towards a wide array of potential applications.

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.

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.

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

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

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

An alternative method of fabricating sub-micron resolution masks using excimer laser ablation

NASA Astrophysics Data System (ADS)

Hayden, C. J.; Eijkel, J. C. T.; Dalton, C.

2004-06-01

In the work presented here, an excimer laser micromachining system has been used successfully to fabricate high-resolution projection and contact masks. The contact masks were subsequently used to produce chrome-gold circular ac electro-osmotic pump (cACEOP) microelectrode arrays on glass substrates, using a conventional contact photolithography process. The contact masks were produced rapidly (~15 min each) and were found to be accurate to sub-micron resolution, demonstrating an alternative route for mask fabrication. Laser machined masks were also used in a laser-projection system, demonstrating that such fabrication techniques are also suited to projection lithography. The work addresses a need for quick reproduction of high-resolution contact masks, given their rapid degradation when compared to non-contact masks.

Reduced Synchronization Persistence in Neural Networks Derived from Atm-Deficient Mice

PubMed Central

Levine-Small, Noah; Yekutieli, Ziv; Aljadeff, Jonathan; Boccaletti, Stefano; Ben-Jacob, Eshel; Barzilai, Ari

2011-01-01

Many neurodegenerative diseases are characterized by malfunction of the DNA damage response. Therefore, it is important to understand the connection between system level neural network behavior and DNA. Neural networks drawn from genetically engineered animals, interfaced with micro-electrode arrays allowed us to unveil connections between networks’ system level activity properties and such genome instability. We discovered that Atm protein deficiency, which in humans leads to progressive motor impairment, leads to a reduced synchronization persistence compared to wild type synchronization, after chemically imposed DNA damage. Not only do these results suggest a role for DNA stability in neural network activity, they also establish an experimental paradigm for empirically determining the role a gene plays on the behavior of a neural network. PMID:21519382

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

A new type of recording chamber with an easy-to-exchange microdrive array for chronic recordings in macaque monkeys.

PubMed

Galashan, F Orlando; Rempel, Hanna C; Meyer, Anneke; Gruber-Dujardin, Eva; Kreiter, Andreas K; Wegener, Detlef

2011-06-01

In monkeys, long-term recordings with chronically implanted microelectrodes frequently suffer from a continuously decreasing probability to record single units or even small multiunit clusters. This problem is associated with two technical limitations of the available devices: first, restrictions for electrode movement, and second, absent possibility to exchange electrodes easily on a regular basis. Permitting to adjust the recording site and to use new recording tracks with proper electrodes may avoid these problems and make chronic more similar to acute recordings. Here, we describe a novel type of implant tackling this issue. It consists of a new type of recording chamber combined with an exchangeable multielectrode array that precisely fits into it. The multielectrode array is reversibly fixed to the chamber, and within a minute it can be exchanged against another array equipped with new electrodes at the awake animal. The array allows for bidirectional movement of six electrodes for a distance of up to 12 mm. The recording chamber enables hermetical isolation of the intracranial space, resulting in long-lasting aseptic conditions and reducing dural thickening to a minimum, as confirmed by microbiological and histopathological analysis. The device has a simple design and is both easy to produce and low in cost. Functionality has been tested in primary and secondary visual cortex of three macaque monkeys over a period of up to 15 mo. The results show that even after more than a year, single and multiunit responses can be obtained with high incidence.

Progress towards biocompatible intracortical microelectrodes for neural interfacing applications

NASA Astrophysics Data System (ADS)

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

2015-02-01

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

Progress Towards Biocompatible Intracortical Microelectrodes for Neural Interfacing Applications

PubMed Central

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

2015-01-01

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

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

PubMed

Tong, Feifei; Lian, Yan; Han, Junliang

2016-12-18

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

Genetic Algorithm Optimization of a Film Cooling Array on a Modern Turbine Inlet Vane

DTIC Science & Technology

2012-09-01

heater is typically higher than the test section temperature since there is a lag due to heat transfer to the piping between the heater and test... flexible substrate 301 used 50 microns thick and the gauges themselves are a platinum metal layer 500-Å thick. When subjected to a change in heat ...more advanced gas turbine cooling design methods that factor in the 3-D flowfield and heat transfer characteristics, this study involves the

The role of tandem duplicator phenotype in tumour evolution in high-grade serous ovarian cancer.

PubMed

Ng, Charlotte K Y; Cooke, Susanna L; Howe, Kevin; Newman, Scott; Xian, Jian; Temple, Jillian; Batty, Elizabeth M; Pole, Jessica C M; Langdon, Simon P; Edwards, Paul A W; Brenton, James D

2012-04-01

High-grade serous ovarian carcinoma (HGSOC) is characterized by genomic instability, ubiquitous TP53 loss, and frequent development of platinum resistance. Loss of homologous recombination (HR) is a mutator phenotype present in 50% of HGSOCs and confers hypersensitivity to platinum treatment. We asked which other mutator phenotypes are present in HGSOC and how they drive the emergence of platinum resistance. We performed whole-genome paired-end sequencing on a model of two HGSOC cases, each consisting of a pair of cell lines established before and after clinical resistance emerged, to describe their structural variants (SVs) and to infer their ancestral genomes as the SVs present within each pair. The first case (PEO1/PEO4), with HR deficiency, acquired translocations and small deletions through its early evolution, but a revertant BRCA2 mutation restoring HR function in the resistant lineage re-stabilized its genome and reduced platinum sensitivity. The second case (PEO14/PEO23) had 216 tandem duplications and did not show evidence of HR or mismatch repair deficiency. By comparing the cell lines to the tissues from which they originated, we showed that the tandem duplicator mutator phenotype arose early in progression in vivo and persisted throughout evolution in vivo and in vitro, which may have enabled continual evolution. From the analysis of SNP array data from 454 HGSOC cases in The Cancer Genome Atlas series, we estimate that 12.8% of cases show patterns of aberrations similar to the tandem duplicator, and this phenotype is mutually exclusive with BRCA1/2 carrier mutations. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A 100 electrode intracortical array: structural variability.

PubMed

Campbell, P K; Jones, K E; Normann, R A

1990-01-01

A technique has been developed for fabricating three dimensional "hair brush" electrode arrays from monocrystalline silicon blocks. Arrays consist of a square pattern of 100 penetrating electrodes, with 400 microns interelectrode spacing. Each electrode is 1.5mm in length and tapers from about 100 microns at its base to a sharp point at the tip. The tips of each electrode are coated with platinum and the entire structure, with the exception of the tips, is insulated with polyimide. Electrical connection to selected electrodes is made by wire bonding polyimide insulated 25 microns diameter gold lead wires to bonding pads on the rear surface of the array. As the geometrical characteristics of the electrodes in such an aray will influence their electrical properties (such as impedance, capacitance, spreading resistance in an electrolyte, etc.) it is desirable that such an array have minimal variability in geometry from electrode to electrode. A study was performed to determine the geometrical variability resulting from our micromachining techniques. Measurements of the diameter of each of the 100 electrodes were made at various planes above the silicon substrate of the array. For the array that was measured, the standard deviation of the diameters was approximately 9% of the mean diameter near the tip, 8% near the middle, and 6% near the base. We describe fabrication techniques which should further reduce these variabilities.

Development of MATLAB software to control data acquisition from a multichannel systems multi-electrode array.

PubMed

Messier, Erik

2016-08-01

A Multichannel Systems (MCS) microelectrode array data acquisition (DAQ) unit is used to collect multichannel electrograms (EGM) from a Langendorff perfused rabbit heart system to study sudden cardiac death (SCD). MCS provides software through which data being processed by the DAQ unit can be displayed and saved, but this software's combined utility with MATLAB is not very effective. MCSs software stores recorded EGM data in a MathCad (MCD) format, which is then converted to a text file format. These text files are very large, and it is therefore very time consuming to import the EGM data into MATLAB for real-time analysis. Therefore, customized MATLAB software was developed to control the acquisition of data from the MCS DAQ unit, and provide specific laboratory accommodations for this study of SCD. The developed DAQ unit control software will be able to accurately: provide real time display of EGM signals; record and save EGM signals in MATLAB in a desired format; and produce real time analysis of the EGM signals; all through an intuitive GUI.

A Thin Film Multifunction Sensor for Harsh Environments

NASA Technical Reports Server (NTRS)

Wrbanek, John D.; Fralick, Gustave C.; Martin, Lisa C.; Blaha, Charles A.

2001-01-01

The status of work at NASA Glenn Research Center to develop a minimally intrusive integrated sensor to provide realtime measurement of strain, heat flux and flow in high temperature environments is presented in this paper. The sensor can be beneficial as a single package to characterize multiple stress and strain modes simultaneously on materials and components during engine development and validation. A major technical challenge is to take existing individual gauge designs and modify them into one integrated thin film sensor. Ultimately, the goal is to develop the ability to deposit the sensors directly onto internal engine parts or on a small thin substrate that can be attached to engine components. Several prototype sensors constructed of platinum, platinum-rhodium alloy, and alumina on constant-strain alumina beams have been built and bench-tested. The technical challenges of the design. construction, and testing are discussed. Data from the preliminary testing of the sensor array is presented. The future direction for the sensor development is discussed as well.

Epoxy-encapsulated ceramic superconductor microelectrodes

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

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

1989-12-01

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

Micromachined electrical cauterizer

DOEpatents

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

1999-01-01

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

Micromachined electrical cauterizer

DOEpatents

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

1999-08-31

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

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

PubMed Central

Rong, Nan; Shan, Baoqing; Wang, Chao

2016-01-01

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

Radiometric infrared focal plane array imaging system for thermographic applications

NASA Technical Reports Server (NTRS)

Esposito, B. J.; Mccafferty, N.; Brown, R.; Tower, J. R.; Kosonocky, W. F.

1992-01-01

This document describes research performed under the Radiometric Infrared Focal Plane Array Imaging System for Thermographic Applications contract. This research investigated the feasibility of using platinum silicide (PtSi) Schottky-barrier infrared focal plane arrays (IR FPAs) for NASA Langley's specific radiometric thermal imaging requirements. The initial goal of this design was to develop a high spatial resolution radiometer with an NETD of 1 percent of the temperature reading over the range of 0 to 250 C. The proposed camera design developed during this study and described in this report provides: (1) high spatial resolution (full-TV resolution); (2) high thermal dynamic range (0 to 250 C); (3) the ability to image rapid, large thermal transients utilizing electronic exposure control (commandable dynamic range of 2,500,000:1 with exposure control latency of 33 ms); (4) high uniformity (0.5 percent nonuniformity after correction); and (5) high thermal resolution (0.1 C at 25 C background and 0.5 C at 250 C background).

Radiometric infrared focal plane array imaging system for thermographic applications

NASA Astrophysics Data System (ADS)

Esposito, B. J.; McCafferty, N.; Brown, R.; Tower, J. R.; Kosonocky, W. F.

1992-11-01

This document describes research performed under the Radiometric Infrared Focal Plane Array Imaging System for Thermographic Applications contract. This research investigated the feasibility of using platinum silicide (PtSi) Schottky-barrier infrared focal plane arrays (IR FPAs) for NASA Langley's specific radiometric thermal imaging requirements. The initial goal of this design was to develop a high spatial resolution radiometer with an NETD of 1 percent of the temperature reading over the range of 0 to 250 C. The proposed camera design developed during this study and described in this report provides: (1) high spatial resolution (full-TV resolution); (2) high thermal dynamic range (0 to 250 C); (3) the ability to image rapid, large thermal transients utilizing electronic exposure control (commandable dynamic range of 2,500,000:1 with exposure control latency of 33 ms); (4) high uniformity (0.5 percent nonuniformity after correction); and (5) high thermal resolution (0.1 C at 25 C background and 0.5 C at 250 C background).