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.

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

PubMed

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

2009-06-15

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

Nanostructured gold microelectrodes for extracellular recording from electrogenic cells.

PubMed

Brüggemann, D; Wolfrum, B; Maybeck, V; Mourzina, Y; Jansen, M; Offenhäusser, A

2011-07-01

We present a new biocompatible nanostructured microelectrode array for extracellular signal recording from electrogenic cells. Microfabrication techniques were combined with a template-assisted approach using nanoporous aluminum oxide to develop gold nanopillar electrodes. The nanopillars were approximately 300-400 nm high and had a diameter of 60 nm. Thus, they yielded a higher surface area of the electrodes resulting in a decreased impedance compared to planar electrodes. The interaction between the large-scale gold nanopillar arrays and cardiac muscle cells (HL-1) was investigated via focused ion beam milling. In the resulting cross-sections we observed a tight coupling between the HL-1 cells and the gold nanostructures. However, the cell membranes did not bend into the cleft between adjacent nanopillars due to the high pillar density. We performed extracellular potential recordings from HL-1 cells with the nanostructured microelectrode arrays. The maximal amplitudes recorded with the nanopillar electrodes were up to 100% higher than those recorded with planar gold electrodes. Increasing the aspect ratio of the gold nanopillars and changing the geometrical layout can further enhance the signal quality in the future.

A 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.

Interdigitated microelectrode based impedance biosensor for detection of salmonella enteritidis in food samples

NASA Astrophysics Data System (ADS)

Kim, G.; Morgan, M.; Hahm, B. K.; Bhunia, A.; Mun, J. H.; Om, A. S.

2008-03-01

Salmonella enteritidis outbreaks continue to occur, and S. enteritidis-related outbreaks from various food sources have increased public awareness of this pathogen. Conventional methods for pathogens detection and identification are labor-intensive and take days to complete. Some immunological rapid assays are developed, but these assays still require prolonged enrichment steps. Recently developed biosensors have shown great potential for the rapid detection of foodborne pathogens. To develop the biosensor, an interdigitated microelectrode (IME) was fabricated by using semiconductor fabrication process. Anti-Salmonella antibodies were immobilized based on avidin-biotin binding on the surface of the IME to form an active sensing layer. To increase the sensitivity of the sensor, three types of sensors that have different electrode gap sizes (2 μm, 5 μm, 10 μm) were fabricated and tested. The impedimetric biosensor could detect 103 CFU/mL of Salmonella in pork meat extract with an incubation time of 5 minutes. This method may provide a simple, rapid and sensitive method to detect foodborne pathogens.

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.

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.

The Removal of Human Breast Cancer Cells from Hematopoietic CD34+ Stem Cells by Dielectrophoretic Field-Flow-Fractionation

PubMed Central

HUANG, YING; YANG, JUN; WANG, XIAO-BO; BECKER, FREDERICK F.; GASCOYNE, PETER R.C.

2009-01-01

Dielectrophoretic field-flow-fractionation (DEP-FFF) was used to purge human breast cancer MDA-435 cells from hematopoietic CD34+ stem cells. An array of interdigitated microelectrodes lining the bottom surface of a thin chamber was used to generate dielectrophoretic forces that levitated the cell mixture in a fluid flow profile. CD34+ stem cells were levitated higher, were carried faster by the fluid flow, and exited the separation chamber earlier than the cancer cells. Using on-line flow cytometry, efficient separation of the cell mixture was observed in less than 12 min, and CD34+ stem cell fractions with a purity >99.2% were obtained. The method of DEP-FFF is potentially applicable to many biomedical cell separation problems, including microfluidic-scale diagnosis and preparative-scale purification of cell subpopulations. PMID:10791899

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

NASA Astrophysics Data System (ADS)

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

2008-12-01

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

An integrated microsystem with dielectrophoresis enrichment and impedance detection for detection of Escherichia coli

USDA-ARS?s Scientific Manuscript database

An integrated microsystem device with matched interdigitated microelectrode chip was fabricated for enrichment and detection of Escherichia coli O157:H7. The microsystem has integrated with positive dielectrophoresis (pDEP) enrichment and in situ impedance detection, whose total volume is only 3.0 ×...

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.

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

NASA Astrophysics Data System (ADS)

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

2006-02-01

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

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...

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.

Improved levitation and trapping of particles by negative dielectrophoresis by the addition of amphoteric molecules

NASA Astrophysics Data System (ADS)

Flores-Rodriguez, Neftali; Markx, Gerard H.

2004-02-01

Addition of amphoteres could be used to improve the levitation and trapping of particles by negative dielectrophoresis. Addition of amphoteric molecules to electromanipulation media increases not only the permittivity of the medium and its viscosity but also its density. To investigate the effect of addition of amphoteres on levitation and trapping by negative dielectrophoresis, the electrokinetic behaviour of latex beads and viable yeast cells (Saccharomyces cerevisiae) was investigated in concentrated solutions of the amphoteric molecules N-[2-hydroxyethyl] piperazine-N'-[2-ethanesulfonic acid] (HEPES) and egr -aminocaproic acid (EACA) using different frequencies and voltages of the applied electrical signal and microelectrodes of different sizes. When using interdigitated electrodes without castellations, latex beads levitated an average of 43% higher when 0.67 M EACA solutions were used and a 54% higher after adding 0.67 M HEPES compared with the levitation heights when no amphoteres were added. Under the same conditions, yeast levitated 78% and 86% higher, respectively. At low voltages and low HEPES/EACA concentrations, the latex particles accumulated in bands between or above the electrodes. However, at the highest voltages and HEPES/EACA concentrations used, the particles formed a network of pearl chains above the electrode arrays. When using electrodes of the interdigitated castellated type of characteristic size 30 µm, latex particles levitated 32% and 40% higher when 0.67 M EACA and HEPES solutions were used in comparison with when no amphoteres were added. At these concentrations, the flow rate needed to dislodge the latex particles from the traps formed by the electric field pattern between the castellations of the interdigitated castellated electrodes was increased by 46% compared with the flow rate needed to achieve this when no amphoteres were added.

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.

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.

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

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

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

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.

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.

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.

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

A sensitive electrochemical immunosensor for label-free detection of Zika-virus protein.

PubMed

Kaushik, Ajeet; Yndart, Adriana; Kumar, Sanjeev; Jayant, Rahul Dev; Vashist, Arti; Brown, Ashley N; Li, Chen-Zhong; Nair, Madhavan

2018-06-26

This work, as a proof of principle, presents a sensitive and selective electrochemical immunosensor for Zika-virus (ZIKV)-protein detection using a functionalized interdigitated micro-electrode of gold (IDE-Au) array. A miniaturized IDE-Au immunosensing chip was prepared via immobilization of ZIKV specific envelop protein antibody (Zev-Abs) onto dithiobis(succinimidyl propionate) i.e., (DTSP) functionalized IDE-Au (electrode gap/width of 10 µm). Electrochemical impedance spectroscopy (EIS) was performed to measure the electrical response of developed sensing chip as a function of ZIKV-protein concentrations. The results of EIS studies confirmed that sensing chip detected ZIKV-protein selectively and exhibited a detection range from 10 pM to 1 nM and a detection limit of 10 pM along with a high sensitivity of 12 kΩM -1 . Such developed ZIKV immune-sensing chip can be integrated with a miniaturized potentiostat (MP)-interfaced with a smartphone for rapid ZIKV-infection detection required for early stage diagnostics at point-of-care application.

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

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

All-solid state, flexible, high-energy integrated hybrid micro-supercapacitors based on 3D LSG/CoNi2S4 nanosheets.

PubMed

Moosavifard, Seyyed Ebrahim; Shamsi, Javad; Altafi, Mohammad Kazem; Moosavifard, Zeinab Sadat

2016-11-18

3D LSG/CoNi 2 S 4 //LSG interdigitated microelectrodes have been firstly developed by a facile, scalable and low cost process for all-solid-state, flexible integrated asymmetric micro-supercapacitors. These devices can achieve energy densities of up to 49 W h l -1 which is comparable to those of lead acid batteries.

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.

Influence of droplet coverage on the electrochemical response of planar microelectrodes and potential solving strategies based on nesting concept

PubMed Central

Yu, Yue

2016-01-01

Recently, biosensors have been widely used for the detection of bacteria, viruses and other toxins. Electrodes, as commonly used transducers, are a vital part of electrochemical biosensors. The coverage of the droplets can change significantly based on the hydrophobicity of the microelectrode surface materials. In the present research, screen-printed interdigitated microelectrodes (SPIMs), as one type of planar microelectrode, were applied to investigate the influence of droplet coverage on electrochemical response. Furthermore, three dimensional (3D) printing technology was employed to print smart devices with different diameters based on the nesting concept. Theoretical explanations were proposed to elucidate the influence of the droplet coverage on the electrochemical response. 3D-printed ring devices were used to incubate the SPIMs and the analytical performances of the SPIMs were tested. According to the results obtained, our device successfully improved the stability of the signal responses and eliminated irregular signal changes to a large extent. Our proposed method based on the nesting concept provides a promising method for the fabrication of stable electrochemical biosensors. We also introduced two types of electrode bases to improve the signal stability. PMID:27635356

Interdigitated array of Pt electrodes for electrical stimulation and engineering of aligned muscle tissue.

PubMed

Ahadian, Samad; Ramón-Azcón, Javier; Ostrovidov, Serge; Camci-Unal, Gulden; Hosseini, Vahid; Kaji, Hirokazu; Ino, Kosuke; Shiku, Hitoshi; Khademhosseini, Ali; Matsue, Tomokazu

2012-09-21

Engineered skeletal muscle tissues could be useful for applications in tissue engineering, drug screening, and bio-robotics. It is well-known that skeletal muscle cells are able to differentiate under electrical stimulation (ES), with an increase in myosin production, along with the formation of myofibers and contractile proteins. In this study, we describe the use of an interdigitated array of electrodes as a novel platform to electrically stimulate engineered muscle tissues. The resulting muscle myofibers were analyzed and quantified in terms of their myotube characteristics and gene expression. The engineered muscle tissues stimulated through the interdigitated array of electrodes demonstrated superior performance and maturation compared to the corresponding tissues stimulated through a conventional setup (i.e., through Pt wires in close proximity to the muscle tissue). In particular, the ES of muscle tissue (voltage 6 V, frequency 1 Hz and duration 10 ms for 1 day) through the interdigitated array of electrodes resulted in a higher degree of C2C12 myotube alignment (∼80%) as compared to ES using Pt wires (∼65%). In addition, higher amounts of C2C12 myotube coverage area, myotube length, muscle transcription factors and protein biomarkers were found for myotubes stimulated through the interdigitated array of electrodes compared to those stimulated using the Pt wires. Due to the wide array of potential applications of ES for two- and three-dimensional (2D and 3D) engineered tissues, the suggested platform could be employed for a variety of cell and tissue structures to more efficiently investigate their response to electrical fields.

Geometric screening of core/shell hydrogel microcapsules using a tapered microchannel with interdigitated electrodes.

PubMed

Niu, Ye; Qi, Lin; Zhang, Fen; Zhao, Yi

2018-07-30

Core/shell hydrogel microcapsules attract increasing research attention due to their potentials in tissue engineering, food engineering, and drug delivery. Current approaches for generating core/shell hydrogel microcapsules suffer from large geometric variations. Geometrically defective core/shell microcapsules need to be removed before further use. High-throughput geometric characterization of such core/shell microcapsules is therefore necessary. In this work, a continuous-flow device was developed to measure the geometric properties of microcapsules with a hydrogel shell and an aqueous core. The microcapsules were pumped through a tapered microchannel patterned with an array of interdigitated microelectrodes. The geometric parameters (the shell thickness and the diameter) were derived from the displacement profiles of the microcapsules. The results show that this approach can successfully distinguish all unencapsulated microparticles. The geometric properties of core/shell microcapsules can be determined with high accuracy. The efficacy of this method was demonstrated through a drug releasing experiment where the optimization of the electrospray process based on geometric screening can lead to controlled and extended drug releasing profiles. This method does not require high-speed optical systems, simplifying the system configuration and making it an indeed miniaturized device. The throughput of up to 584 microcapsules per minute was achieved. This study provides a powerful tool for screening core/shell hydrogel microcapsules and is expected to facilitate the applications of these microcapsules in various fields. Copyright © 2018 Elsevier B.V. All rights reserved.

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...

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.

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.

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.

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 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.

High-density CMOS Microelectrode Array System for Impedance Spectroscopy and Imaging of Biological Cells.

PubMed

Vijay, Viswam; Raziyeh, Bounik; Amir, Shadmani; Jelena, Dragas; Alicia, Boos Julia; Axel, Birchler; Jan, Müller; Yihui, Chen; Andreas, Hierlemann

2017-01-26

A monolithic measurement platform was implemented to enable label-free in-vitro electrical impedance spectroscopy measurements of cells on multi-functional CMOS microelectrode array. The array includes 59,760 platinum microelectrodes, densely packed within a 4.5 mm × 2.5 mm sensing region at a pitch of 13.5 μm. The 32 on-chip lock-in amplifiers can be used to measure the impedance of any arbitrarily chosen electrodes on the array by applying a sinusoidal voltage, generated by an on-chip waveform generator with a frequency range from 1 Hz to 1 MHz, and measuring the respective current. Proof-of-concept measurements of impedance sensing and imaging are shown in this paper. Correlations between cell detection through optical microscopy and electrochemical impedance scanning were established.

Surface-enhanced Raman spectroscopy on litographically constructed microelectrodes

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

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

1995-12-31

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

Robust Functionalization of Large Microelectrode Arrays by Using Pulsed Potentiostatic Deposition

PubMed Central

Rothe, Joerg; Frey, Olivier; Madangopal, Rajtarun; Rickus, Jenna; Hierlemann, Andreas

2016-01-01

Surface modification of microelectrodes is a central step in the development of microsensors and microsensor arrays. Here, we present an electrodeposition scheme based on voltage pulses. Key features of this method are uniformity in the deposited electrode coatings, flexibility in the overall deposition area, i.e., the sizes and number of the electrodes to be coated, and precise control of the surface texture. Deposition and characterization of four different materials are demonstrated, including layers of high-surface-area platinum, gold, conducting polymer poly(ethylenedioxythiophene), also known as PEDOT, and the non-conducting polymer poly(phenylenediamine), also known as PPD. The depositions were conducted using a fully integrated complementary metal-oxide-semiconductor (CMOS) chip with an array of 1024 microelectrodes. The pulsed potentiostatic deposition scheme is particularly suitable for functionalization of individual electrodes or electrode subsets of large integrated microelectrode arrays: the required deposition waveforms are readily available in an integrated system, the same deposition parameters can be used to functionalize the surface of either single electrodes or large arrays of thousands of electrodes, and the deposition method proved to be robust and reproducible for all materials tested. PMID:28025569

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.

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...

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

PubMed

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

2012-05-15

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

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...

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.

Selective deposition of nanostructured ruthenium oxide using Tobacco mosaic virus for micro-supercapacitors in solid Nafion electrolyte

NASA Astrophysics Data System (ADS)

Gnerlich, Markus; Ben-Yoav, Hadar; Culver, James N.; Ketchum, Douglas R.; Ghodssi, Reza

2015-10-01

A three-dimensional micro-supercapacitor has been developed using a novel bottom-up assembly method combining genetically modified Tobacco mosaic virus (TMV-1Cys), photolithographically defined micropillars and selective deposition of ruthenium oxide on multi-metallic microelectrodes. The three-dimensional microelectrodes consist of a titanium nitride current collector with two functionalized areas: (1) gold coating on the active electrode area promotes TMV-1Cys adhesion, and (2) sacrificial nickel pads dissolve in ruthenium tetroxide plating solution to produce ruthenium oxide on all electrically connected areas. The microfabricated electrodes are arranged in an interdigitated pattern, and the capacitance per electrode has been measured as high as 203 mF cm-2 with solid Nafion electrolyte. The process integration of bio-templated ruthenium oxide with microfabricated electrodes and solid electrolyte is an important advance towards the energy storage needs of mass produced self-sufficient micro-devices.

Selective deposition of nanostructured ruthenium oxide using Tobacco mosaic virus for micro-supercapacitors in solid Nafion electrolyte

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

Gnerlich, Markus; Ben-Yoav, Hadar; Culver, James N.

A three-dimensional micro-supercapacitor has been developed using a novel bottom-up assembly method combining genetically modified Tobacco mosaic virus (TMV-1Cys), photolithographically defined micropillars and selective deposition of ruthenium oxide on multi-metallic microelectrodes. The three-dimensional microelectrodes consist of a titanium nitride current collector with two functionalized areas: (1) gold coating on the active electrode area promotes TMV-1Cys adhesion, and (2) sacrificial nickel pads dissolve in ruthenium tetroxide plating solution to produce ruthenium oxide on all electrically connected areas. The microfabricated electrodes are arranged in an interdigitated pattern, and the capacitance per electrode has been measured as high as 203 mF cm-2 withmore » solid Nafion electrolyte. The process integration of bio-templated ruthenium oxide with microfabricated electrodes and solid electrolyte is an important advance towards the energy storage needs of mass produced self-sufficient micro-devices.« less

Addressing of LnCaP Cell Using Magnetic Particles Assisted Impedimetric Microelectrode.

PubMed

Nguyen, Dung Thi Xuan; Tran, Trong Binh; Nguyen, Phuong-Diem; Min, Junhong

2016-03-01

In this study, we provide a facile, effective technique for a simple isolation and enrichment of low metastatic prostate tumor cell LNCaP using biocompatible, magnetic particles asissted impedimetric sensing system. Hydrophobic cell membrane anchors (BAM) were generated onto magnetic particles which diameters vary from 50 nm to 5 μm and were used to capture LNCaP cells from the suspension. Finally, magnetic particle-LNCaP complex were addressed onto the surface of the interdigitated microelectrode (IDM). Cell viability was monitored by our laboratory developed-technique Electrical Cell Substrate Impedance Sensing (ECIS). The results reavealed that 50 nm-magnetic particles showed best performance in terms of cell separation and cell viability. This technique provides a simple and efficient method for the direct addressing of LNCaP cell on the surface and enhances better understanding of cell behavior for cancer management in the near future.

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...

Inkjet printing and electrical characterisation of DNA-templated cadmium sulphide nanowires

NASA Astrophysics Data System (ADS)

Nurdillayeva, R. N.; Oshido, A. B.; Bamford, T. A.; El-Zubir, O.; Houlton, A.; Hedley, J.; Pike, A. R.; Horrocks, B. R.

2018-04-01

Cadmium sulphide can be templated on λ-DNA molecules to form an aqueous dispersion of CdS/λ-DNA nanowires. Subsequent addition of ethylene glycol to 50% v/v is sufficient to formulate an ink suitable for printing using piezoelectric drop-on-demand technology. Printed droplet arrays show a coffee-ring morphology of individual deposits by fluorescence and Raman microscopy, but upon increasing the number of layers of printed material by repeated printing over each droplet, the dry deposit approaches closer to a disc shape. It is also possible to print parallel tracks by reducing the droplet separation in the array until neighbouring droplets overlap before they dry. The droplets coalesce to form a strip of width roughly equal to the diameter of the droplets. Evaporation-driven capillary flow sends the nanowires to the edges of the strip and when dry they form parallel tracks of CdS/λ-DNA nanowire bundles. Both droplets and tracks were printed onto Pt-on-glass interdigitated microelectrodes (10 μm width, 10 μm gap). The current-voltage characteristics of these two-terminal devices were approximately ohmic, but with some hysteresis. The conductance increased with temperature as a simple activated process with activation energies of 0.57 ± 0.02 eV (tracks) and 0.39 ± 0.02 eV (droplets). The impedance spectra of the printed films were consistent with hopping between CdS grains.

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

Feasibility Study of Extended-Gate-Type Silicon Nanowire Field-Effect Transistors for Neural Recording

PubMed Central

Kang, Hongki; Kim, Jee-Yeon; Choi, Yang-Kyu; Nam, Yoonkey

2017-01-01

In this research, a high performance silicon nanowire field-effect transistor (transconductance as high as 34 µS and sensitivity as 84 nS/mV) is extensively studied and directly compared with planar passive microelectrode arrays for neural recording application. Electrical and electrochemical characteristics are carefully characterized in a very well-controlled manner. We especially focused on the signal amplification capability and intrinsic noise of the transistors. A neural recording system using both silicon nanowire field-effect transistor-based active-type microelectrode array and platinum black microelectrode-based passive-type microelectrode array are implemented and compared. An artificial neural spike signal is supplied as input to both arrays through a buffer solution and recorded simultaneously. Recorded signal intensity by the silicon nanowire transistor was precisely determined by an electrical characteristic of the transistor, transconductance. Signal-to-noise ratio was found to be strongly dependent upon the intrinsic 1/f noise of the silicon nanowire transistor. We found how signal strength is determined and how intrinsic noise of the transistor determines signal-to-noise ratio of the recorded neural signals. This study provides in-depth understanding of the overall neural recording mechanism using silicon nanowire transistors and solid design guideline for further improvement and development. PMID:28350370

Feasibility Study of Extended-Gate-Type Silicon Nanowire Field-Effect Transistors for Neural Recording.

PubMed

Kang, Hongki; Kim, Jee-Yeon; Choi, Yang-Kyu; Nam, Yoonkey

2017-03-28

In this research, a high performance silicon nanowire field-effect transistor (transconductance as high as 34 µS and sensitivity as 84 nS/mV) is extensively studied and directly compared with planar passive microelectrode arrays for neural recording application. Electrical and electrochemical characteristics are carefully characterized in a very well-controlled manner. We especially focused on the signal amplification capability and intrinsic noise of the transistors. A neural recording system using both silicon nanowire field-effect transistor-based active-type microelectrode array and platinum black microelectrode-based passive-type microelectrode array are implemented and compared. An artificial neural spike signal is supplied as input to both arrays through a buffer solution and recorded simultaneously. Recorded signal intensity by the silicon nanowire transistor was precisely determined by an electrical characteristic of the transistor, transconductance. Signal-to-noise ratio was found to be strongly dependent upon the intrinsic 1/f noise of the silicon nanowire transistor. We found how signal strength is determined and how intrinsic noise of the transistor determines signal-to-noise ratio of the recorded neural signals. This study provides in-depth understanding of the overall neural recording mechanism using silicon nanowire transistors and solid design guideline for further improvement and development.

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

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.

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.

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

PubMed Central

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

2017-01-01

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

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.

Simultaneous Measurements of Geometric and Viscoelastic Properties of Hydrogel Microbeads Using Continuous-Flow Microfluidics with Embedded Electrodes.

PubMed

Niu, Ye; Zhang, Xu; Si, Ting; Zhang, Yuntian; Qi, Lin; Zhao, Gang; Xu, Ronald X; He, Xiaoming; Zhao, Yi

2017-12-01

Geometric and mechanical characterizations of hydrogel materials at the microscale are attracting increasing attention due to their importance in tissue engineering, regenerative medicine, and drug delivery applications. Contemporary approaches for measuring the these properties of hydrogel microbeads suffer from low-throughput, complex system configuration, and measurement inaccuracy. In this work, a continuous-flow device is developed to measure geometric and viscoelastic properties of hydrogel microbeads by flowing the microbeads through a tapered microchannel with an array of interdigitated microelectrodes patterned underneath the channel. The viscoelastic properties are derived from the trajectories of microbeads using a quasi-linear viscoelastic model. The measurement is independent of the applied volumetric flow rate. The results show that the geometric and viscoelastic properties of Ca-alginate hydrogel microbeads can be determined independently and simultaneously. The bulky high-speed optical systems are eliminated, simplifying the system configuration and making it a truly miniaturized device. A throughput of up to 394 microbeads min -1 is achieved. This study may provide a powerful tool for mechanical profiling of hydrogel microbeads to support their wide applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A wideband superconducting filter at Ku-band based on interdigital coupling

NASA Astrophysics Data System (ADS)

Jiang, Ying; Wei, Bin; Cao, Bisong; Li, Qirong; Guo, Xubo; Jiang, Linan; Song, Xiaoke; Wang, Xiang

2018-04-01

In this paper, an interdigital-type resonator with strong electric coupling is proposed for the wideband high-frequency (>10 GHz) filter design. The proposed microstrip resonator consists of an H-shaped main line part with its both ends installed with interdigital finger parts. Strong electric coupling is achieved between adjacent resonators. A six-pole high-temperature superconducting filter at Ku-band using this resonator is designed and fabricated. The filter has a center frequency of 15.11 GHz with a fractional bandwidth of 30%. The insertion loss of the passband is less than 0.3 dB, and the return loss is greater than 14 dB without any tuning.

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

Characterization of immobilization methods of antiviral antibodies in serum for electrochemical biosensors

NASA Astrophysics Data System (ADS)

Huy, Tran Quang; Hanh, Nguyen Thi Hong; Van Chung, Pham; Anh, Dang Duc; Nga, Phan Thi; Tuan, Mai Anh

2011-06-01

In this paper, we describes different methods to immobilize Japanese encephalitis virus (JEV) antibodies in human serum onto the interdigitated surface of a microelectrode sensor for optimizing electrochemical detection: (1) direct covalent binding to the silanized surface, (2) binding to the silanized surface via a cross-linker of glutaraldehyde (GA), (3) binding to glutaraldehyde/silanized surface via goat anti-human IgG polyclonal antibody and (4) binding to glutaraldehyde/silanized surface via protein A (PrA). Field emission scanning electron microscopy, Fourier transform infrared spectrometry, and fluorescence microscopy are used to verify the characteristics of antibodies on the interdigitated surface after the serum antibodies immobilization. The analyzed results indicate that the use of protein A is an effective choice for immobilization and orientation of antibodies in serum for electrochemical biosensors. This study provides an advantageous immobilization method of serum containing antiviral antibodies to develop electrochemical biosensors for preliminary screening of viruses in clinical samples from outbreaks.

Label-free electrochemical detection of botulinum neurotoxin type E based on its enzymatic activity using interdigitated electrodes

NASA Astrophysics Data System (ADS)

Hyun, Sang Hwa; Park, Dae Keun; Kang, Aeyeon; Kim, Soohyun; Kim, Daehee; Shin, Yu Mi; Song, Ji-Joon; Yun, Wan Soo

2016-02-01

We report a simple label-free electrochemical method of detecting low concentrations of botulinum neurotoxin type E light chain (BoNT/E LC) based on its peptide cleavage activity. Dual-mode cyclic voltammetry was employed to observe changes in the redox signal of ferri-/ferro-cyanide on interdigitated microelectrodes, whose surfaces were covered by peptides designed from synaptosomal-associated protein 25 to be cleaved by BoNT/E LC. With the introduction of BoNT/E LC, the redox signal showed a time-dependent increase due to cleavage of the immobilized peptide molecules. In addition to the increased redox signal intensity, its time-dependence can be considered as a strong evidence of BoNT/E sensing, since the time-dependent increase can only result from the enzymatic activity of BoNT/E LC. Using this method, BoNT/E LC, at concentrations as low as 5 pg/ml, was readily measurable with only an hour of incubation.

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

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

Electrogenerated Chemiluminescence of BODIPY, Ru(bpy)32+, and 9,10-Diphenylanthracene Using Interdigitated Array Electrodes

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

Nepomnyashchii, Alexander B.; Kolesov, Grigory; Parkinson, Bruce A.

Interdigitated array electrodes (IDAs) were used to produce steady-state electrogenerated chemiluminescence (ECL) by annihilation of oxidized and reduced forms of a substituted boron dipyrromethene (BODIPY) dye, 9,10-diphenylanthracene (DPA), and ruthenium(II) tris(bypiridine) (Ru-(bpy)32+). Digital simulations were in good agreement with the experimentally obtained currents and light outputs. Coreactant experiments, using tri-n-propylamine and benzoyl peroxide as a sacrificial homogeneous reductant or oxidant, show currents corresponding to electrode reactions of the dyes and not the oxidation or reduction of the coreactants. The results show that interdigitated arrays can produce stable ECL where the light intensity is magnified due to the larger currents asmore » a consequence of feedback between generator and collector electrodes in the IDA. The light output for ECL is around 100 times higher than that obtained with regular planar electrodes with similar area. This material is based upon work supported as part of the Center of Molecular Electrocatalysis, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences.« less

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-01-01

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

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

PubMed

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

2004-05-15

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

Impedimetric detection of bacteria by using a microfluidic chip and silver nanoparticle based signal enhancement.

PubMed

Wang, Renjie; Xu, Yi; Sors, Thomas; Irudayaraj, Joseph; Ren, Wen; Wang, Rong

2018-02-19

The authors describe a method that can significantly improve the performance of impedimetric detection of bacteria. A multifunctional microfluidic chip was designed consisting of interdigitated microelectrodes and a micro-mixing zone with a Tesla structure. This maximizes the coating of bacterial surfaces with nanoparticles and results in improved impedimetric detection. The method was applied to the detection of Escherichia coli O157:H7 (E. coli). Silver enhancement was accomplished by coating E.coli with the cationic polymer diallyldimethylammonium chloride (PDDA) to form positively charged E. coli/PDDA complexes. Then, gold nanoparticles (AuNPs) were added, and the resulting E. coli/PDDA/AuNPs complexes were collected at interdigitated electrodes via positive dielectrophoresis (pDEP). A silver adduct was then formed on the E. coli/PDDA/AuNP complexes by using silver enhancement solutions and by using the AuNPs as catalysts. The combination of pDEP based capture and of using silver adducts reduces impedance by increasing the conductivity of the solution and the double layer capacitance around the microelectrodes. Impedance decreases linearly in the 2 × 10 3 -2 × 10 5  cfu·mL -1 E. coli concentration range, with a 500 cfu·mL -1 detection limit. Egg shell wash samples and tap water spiked with E. coli were successfully used for validation, and this demonstrates the practical application of this method. Graphical abstract Schematic representation of the AuNP@Ag enhancement method integrated with multifunctional microfluidic chip platform for impedimetric quantitation of bacteria. The method significantly improves the performance of impedimetric detection of bacteria.

Interdigital pair bonding for high frequency (20-50 MHz) ultrasonic composite transducers.

PubMed

Liu, R; Harasiewicz, K A; Foster, F S

2001-01-01

Interdigital pair bonding is a novel methodology that enables the fabrication of high frequency piezoelectric composites with high volume fractions of the ceramic phase. This enhancement in ceramic volume fraction significantly reduces the dimensional scale of the epoxy phase and increases the related effective physical parameters of the composite, such as dielectric constant and the longitudinal sound velocity, which are major concerns in the development of high frequency piezoelectric composites. In this paper, a method called interdigital pair bonding (IPB) is used to prepare 1-3 piezoelectric composite with a pitch of 40 microns, a kerf of 4 microns, and a ceramic volume fraction of 81%. The composites prepared in this fashion exhibited a very pure thickness-mode resonance up to a frequency of 50 MHz. Unlike the 2-2 piezoelectric composites with the same ceramic and epoxy scales developed earlier, the anticipated lateral modes between 50 to 100 MHz were not observed in the current 1-3 composites. The mechanisms for the elimination of the lateral modes at high frequency are discussed. The effective electromechanical coupling coefficient of the composite was 0.72 at a frequency of 50 MHz. The composites showed a high longitudinal sound velocity of 4300 m/s and a high clamped dielectric constant of 1111 epsilon 0, which will benefit the development of high frequency ultrasonic transducers and especially high frequency transducer arrays for medical imaging.

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

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

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 Sensitive DNA Capacitive Biosensor Using Interdigitated Electrodes

PubMed Central

Wang, Lei; Veselinovic, Milena; Yang, Lang; Geiss, Brian J.; Dandy, David S.; Chen, Tom

2017-01-01

This paper presents a label-free affinity-based capacitive biosensor using interdigitated electrodes. Using an optimized process of DNA probe preparation to minimize the effect of contaminants in commercial thiolated DNA probe, the electrode surface was functionalized with the 24-nucleotide DNA probes based on the West Nile virus sequence (Kunjin strain). The biosensor has the ability to detect complementary DNA fragments with a detection limit down to 20 DNA target molecules (1.5 aM range), making it suitable for a practical point-of-care (POC) platform for low target count clinical applications without the need for amplification. The reproducibility of the biosensor detection was improved with efficient covalent immobilization of purified single-stranded DNA probe oligomers on cleaned gold microelectrodes. In addition to the low detection limit, the biosensor showed a dynamic range of detection from 1 μL−1 to 105 μL−1 target molecules (20 to 2 million targets), making it suitable for sample analysis in a typical clinical application environment. The binding results presented in this paper were validated using fluorescent oligomers. PMID:27619528

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.

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

PubMed

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

2017-10-20

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

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.

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

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.

Femtosecond laser micromachining of polylactic acid/graphene composites for designing interdigitated microelectrodes for sensor applications

NASA Astrophysics Data System (ADS)

Paula, Kelly T.; Gaál, Gabriel; Almeida, G. F. B.; Andrade, M. B.; Facure, Murilo H. M.; Correa, Daniel S.; Riul, Antonio; Rodrigues, Varlei; Mendonça, Cleber R.

2018-05-01

There is an increasing interest in the last years towards electronic applications of graphene-based materials and devices fabricated from patterning techniques, with the ultimate goal of high performance and temporal resolution. Laser micromachining using femtosecond pulses is an attractive methodology to integrate graphene-based materials into functional devices as it allows changes to the focal volume with a submicrometer spatial resolution due to the efficient nonlinear nature of the absorption, yielding rapid prototyping for innovative applications. We present here the patterning of PLA-graphene films spin-coated on a glass substrate using a fs-laser at moderate pulse energies to fabricate interdigitated electrodes having a minimum spatial resolution of 5 μm. Raman spectroscopy of the PLA-graphene films indicated the presence of multilayered graphene fibers. Subsequently, the PLA-graphene films were micromachined using a femtosecond laser oscillator delivering 50-fs pulses and 800 nm, where the pulse energy and scanning speed was varied in order to determine the optimum irradiation parameters (16 nJ and 100 μm/s) to the fabrication of microstructures. The micromachined patterns were characterized by optical microscopy and submitted to electrical measurements in liquid samples, clearly distinguishing all tastes tested. Our results confirm the femtosecond laser micromachining technique as an interesting approach to efficiently pattern PLA-graphene filaments with high precision and minimal mechanical defects, allowing the easy fabrication of interdigitated structures and an alternative method to those produced by conventional photolithography.

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.

Polymeric lithography editor: Editing lithographic errors with nanoporous polymeric probes

PubMed Central

Rajasekaran, Pradeep Ramiah; Zhou, Chuanhong; Dasari, Mallika; Voss, Kay-Obbe; Trautmann, Christina; Kohli, Punit

2017-01-01

A new lithographic editing system with an ability to erase and rectify errors in microscale with real-time optical feedback is demonstrated. The erasing probe is a conically shaped hydrogel (tip size, ca. 500 nm) template-synthesized from track-etched conical glass wafers. The “nanosponge” hydrogel probe “erases” patterns by hydrating and absorbing molecules into a porous hydrogel matrix via diffusion analogous to a wet sponge. The presence of an interfacial liquid water layer between the hydrogel tip and the substrate during erasing enables frictionless, uninterrupted translation of the eraser on the substrate. The erasing capacity of the hydrogel is extremely high because of the large free volume of the hydrogel matrix. The fast frictionless translocation and interfacial hydration resulted in an extremely high erasing rate (~785 μm2/s), which is two to three orders of magnitude higher in comparison with the atomic force microscopy–based erasing (~0.1 μm2/s) experiments. The high precision and accuracy of the polymeric lithography editor (PLE) system stemmed from coupling piezoelectric actuators to an inverted optical microscope. Subsequently after erasing the patterns using agarose erasers, a polydimethylsiloxane probe fabricated from the same conical track-etched template was used to precisely redeposit molecules of interest at the erased spots. PLE also provides a continuous optical feedback throughout the entire molecular editing process—writing, erasing, and rewriting. To demonstrate its potential in device fabrication, we used PLE to electrochemically erase metallic copper thin film, forming an interdigitated array of microelectrodes for the fabrication of a functional microphotodetector device. High-throughput dot and line erasing, writing with the conical “wet nanosponge,” and continuous optical feedback make PLE complementary to the existing catalog of nanolithographic/microlithographic and three-dimensional printing techniques. This new PLE technique will potentially open up many new and exciting avenues in lithography, which remain unexplored due to the inherent limitations in error rectification capabilities of the existing lithographic techniques. PMID:28630898

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

PubMed

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

2005-03-01

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

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.

Deep brain stimulation macroelectrodes compared to multiple microelectrodes in rat hippocampus

PubMed Central

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

2014-01-01

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

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

Chemiresistor urea sensor

DOEpatents

Glass, Robert S.

1997-01-01

A sensor to detect and quantify urea in fluids resulting from hemodialysis procedures, and in blood and other body fluids. The sensor is based upon a chemiresistor, which consists of an interdigitated array of metal fingers between which a resistance measured. The interdigitated array is fabricated on a suitable substrate. The surface of the array of fingers is covered with a coating containing the enzyme urease which catalyzes the hydrolysis of urea to form the ammonium ion, the bicarbonate ion, and hydroxide-chemical products which provide the basis for the measured signal. In a typical application, the sensor could be used at bedside, in conjunction with an appropriate electronics/computer system, in order to determine the hemodialysis endpoint. Also, the chemiresistor used to detect urea, can be utilized with a reference chemiresistor which does not contain urease, and connected in a differential measurement arrangement, such that the reference chemiresistor would cancel out any fluctuations due to background effects.

Thermoacoustic chips with carbon nanotube thin yarn arrays.

PubMed

Wei, Yang; Lin, Xiaoyang; Jiang, Kaili; Liu, Peng; Li, Qunqing; Fan, Shoushan

2013-10-09

Aligned carbon nanotube (CNT) films drawn from CNT arrays have shown the potential as thermoacoustic loudspeakers. CNT thermoacoustic chips with robust structures are proposed to promote the applications. The silicon-based chips can play sound and fascinating rhythms by feeding alternating currents and audio signal to the suspending CNT thin yarn arrays across grooves in them. In additional to the thin yarns, experiments further revealed more essential elements of the chips, the groove depth and the interdigital electrodes. The sound pressure depends on the depth of the grooves, and the thermal wavelength can be introduced to define the influence-free depth. The interdigital fingers can effectively reduce the driving voltage, making the chips safe and easy to use. The chips were successfully assembled into earphones and have been working stably for about one year. The thermoacoustic chips can find many applications in consumer electronics and possibly improve the audiovisual experience.

Chemiresistor urea sensor

DOEpatents

Glass, R.S.

1997-12-16

A sensor is disclosed to detect and quantify urea in fluids resulting from hemodialysis procedures, and in blood and other body fluids. The sensor is based upon a chemiresistor, which consists of an interdigitated array of metal fingers between which a resistance measured. The interdigitated array is fabricated on a suitable substrate. The surface of the array of fingers is covered with a coating containing the enzyme urease which catalyzes the hydrolysis of urea to form the ammonium ion, the bicarbonate ion, and hydroxide-chemical products which provide the basis for the measured signal. In a typical application, the sensor could be used at bedside, in conjunction with an appropriate electronics/computer system, in order to determine the hemodialysis endpoint. Also, the chemiresistor used to detect urea, can be utilized with a reference chemiresistor which does not contain urease, and connected in a differential measurement arrangement, such that the reference chemiresistor would cancel out any fluctuations due to background effects. 16 figs.

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.

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.

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.

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

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.

Ultrasonic studies of high-temperature superconductors

NASA Astrophysics Data System (ADS)

Feller, Jeffrey Robert

1997-09-01

This dissertation consists roughly of two parts. The first part deals with YBa2Cu3O7-δ (YBCO) films deposited on piezoelectric (LiNbO3) substrates. Interdigital surface acoustic wave (SAW) devices (delay lines operating at center frequencies of 50 and 100 MHz) fabricated from YBCO films are examined; insertion loss measurements are presented, and electrode resistance effects are analyzed using equivalent circuit models. Sheet resistance and 168 MHz SAW attenuation measurements of a granular YBCO film on LiNbO3 are also presented. The experimental data are discussed in terms of a percolation theory that models the film as an array of identical YBCO grains connected by resistive junctions which, in the superconducting state behave as Josephson junctions. The normal state resistances of the junctions are assumed to be randomly distributed. In the second part of the dissertation, a number of novel techniques (SAW 'bridges,' the high frequency interdigital proximity probe, and weak acoustic coupling sampled continuous wave spectrometry), used in the study of the vortex state and structural transitions in the normal state of YBCO films and single crystals, are described. Evidence of the existence of a first order structural transition in the vicinity of 220 K is provided.

Changing gears from chemical adhesion of cells to flat substrata toward engulfment of micro-protrusions by active mechanisms

NASA Astrophysics Data System (ADS)

Hai, Aviad; Kamber, Dotan; Malkinson, Guy; Erez, Hadas; Mazurski, Noa; Shappir, Joseph; Spira, Micha E.

2009-12-01

Microelectrode arrays increasingly serve to extracellularly record in parallel electrical activity from many excitable cells without inflicting damage to the cells by insertion of microelectrodes. Nevertheless, apart from rare cases they suffer from a low signal to noise ratio. The limiting factor for effective electrical coupling is the low seal resistance formed between the plasma membrane and the electronic device. Using transmission electron microscope analysis we recently reported that cultured Aplysia neurons engulf protruding micron size gold spines forming tight apposition which significantly improves the electrical coupling in comparison with flat electrodes (Hai et al 2009 Spine-shaped gold protrusions improve the adherence and electrical coupling of neurons with the surface of micro-electronic devices J. R. Soc. Interface 6 1153-65). However, the use of a transmission electron microscope to measure the extracellular cleft formed between the plasma membrane and the gold-spine surface may be inaccurate as chemical fixation may generate structural artifacts. Using live confocal microscope imaging we report here that cultured Aplysia neurons engulf protruding spine-shaped gold structures functionalized by an RGD-based peptide and to a significantly lesser extent by poly-l-lysine. The cytoskeletal elements actin and associated protein cortactin are shown to organize around the stalks of the engulfed gold spines in the form of rings. Neurons grown on the gold-spine matrix display varying growth patterns but maintain normal electrophysiological properties and form functioning synapses. It is concluded that the matrices of functionalized gold spines provide an improved substrate for the assembly of neuro-electronic hybrids.

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

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.

Portable Ultrasonic Guided Wave Inspection with MACRO Fiber Composite Actuators

NASA Astrophysics Data System (ADS)

Haig, A.; Mudge, P.; Catton, P.; Balachandran, W.

2010-02-01

The development of portable ultrasonic guided wave transducer arrays that utilize Macro Fiber Composite actuators (MFCs) is described. Portable inspection equipment can make use of ultrasonic guided waves to rapidly screen large areas of many types of engineering structures for defects. The defect finding performance combined with the difficulty of application determines how much the engineering industry makes use of this non-destructive, non-disruptive technology. The developments with MFCs have the potential to make considerable improvements in both these aspects. MFCs are highly efficient because they use interdigital electrodes to facilitate the extensional, d33 displacement mode. Their fiber composite design allows them to be thin, lightweight, flexible and durable. The flexibility affords them conformance with curved surfaces, which can facilitate good mechanical coupling. The suitability of a given transducer for Long Range Ultrasonic Testing is governed by the nature and amplitude of the displacement that it excites/senses in the contact area of the target structure. This nature is explored for MFCs through directional sensitivity analysis and empirical testing. Housing methods that facilitate non-permanent coupling techniques are discussed. Finally, arrangements of arrays of MFCs for the guided wave inspection of plates and pipes are considered and some broad design criteria are given.

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.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-01-01

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

Fast batch injection analysis of H(2)O(2) using an array of Pt-modified gold microelectrodes obtained from split electronic chips.

PubMed

Pacheco, Bruno D; Valério, Jaqueline; Angnes, Lúcio; Pedrotti, Jairo J

2011-06-24

A fast and robust analytical method for amperometric determination of hydrogen peroxide (H(2)O(2)) based on batch injection analysis (BIA) on an array of gold microelectrodes modified with platinum is proposed. The gold microelectrode array (n=14) was obtained from electronic chips developed for surface mounted device technology (SMD), whose size offers advantages to adapt them in batch cells. The effect of the dispensing rate, volume injected, distance between the platinum microelectrodes and the pipette tip, as well as the volume of solution in the cell on the analytical response were evaluated. The method allows the H(2)O(2) amperometric determination in the concentration range from 0.8 μmolL(-1) to 100 μmolL(-1). The analytical frequency can attain 300 determinations per hour and the detection limit was estimated in 0.34 μmolL(-1) (3σ). The anodic current peaks obtained after a series of 23 successive injections of 50 μL of 25 μmolL(-1) H(2)O(2) showed an RSD<0.9%. To ensure the good selectivity to detect H(2)O(2), its determination was performed in a differential mode, with selective destruction of the H(2)O(2) with catalase in 10 mmolL(-1) phosphate buffer solution. Practical application of the analytical procedure involved H(2)O(2) determination in rainwater of São Paulo City. A comparison of the results obtained by the proposed amperometric method with another one which combines flow injection analysis (FIA) with spectrophotometric detection showed good agreement. Copyright © 2011 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-01-01

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

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.

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

A 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.

Reduction of the spatially mutual coupling between dual-polarized patch antennas using coupled metamaterial slabs.

PubMed

Pan, Bai Cao; Tang, Wen Xuan; Qi, Mei Qing; Ma, Hui Feng; Tao, Zui; Cui, Tie Jun

2016-07-22

Mutual coupling inside antenna array is usually caused by two routes: signal leakage via conducting currents on the metallic background or surface wave along substrates; radio leakage received from space between antenna elements. The former one can be depressed by changing the distribution of surface currents, as reported in literatures. But when it comes to the latter one, the radiation-leakage-caused coupling, traditional approaches using circuit manipulation may be inefficient. In this article, we propose and design a new type of decoupling module, which is composed of coupled metamaterial (MTM) slabs. Two classes of MTM particles, the interdigital structure (IS) and the split-ring resonators (SRRs), are adopted to provide the first and second modulations of signal. We validate its function to reduce the radiation leakage between two dual-polarized patch antennas. A prototype is fabricated in a volume with subwavelength scale (0.6λ × 0.3λ × 0.053λ) to provide 7dB improvement for both co-polarization and cross-polarization isolations from 1.95 to 2.2 GHz. The design has good potential for wireless communication and radar systems.

Reduction of the spatially mutual coupling between dual-polarized patch antennas using coupled metamaterial slabs

PubMed Central

Pan, Bai Cao; Tang, Wen Xuan; Qi, Mei Qing; Ma, Hui Feng; Tao, Zui; Cui, Tie Jun

2016-01-01

Mutual coupling inside antenna array is usually caused by two routes: signal leakage via conducting currents on the metallic background or surface wave along substrates; radio leakage received from space between antenna elements. The former one can be depressed by changing the distribution of surface currents, as reported in literatures. But when it comes to the latter one, the radiation-leakage-caused coupling, traditional approaches using circuit manipulation may be inefficient. In this article, we propose and design a new type of decoupling module, which is composed of coupled metamaterial (MTM) slabs. Two classes of MTM particles, the interdigital structure (IS) and the split-ring resonators (SRRs), are adopted to provide the first and second modulations of signal. We validate its function to reduce the radiation leakage between two dual-polarized patch antennas. A prototype is fabricated in a volume with subwavelength scale (0.6λ × 0.3λ × 0.053λ) to provide 7dB improvement for both co-polarization and cross-polarization isolations from 1.95 to 2.2 GHz. The design has good potential for wireless communication and radar systems. PMID:27444147

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

Effects of Mechanical Coupling Between Cardiomyocytes and Cardiac Fibroblasts on Myocardium

NASA Astrophysics Data System (ADS)

Zorlutuna, Pinar; Nguyen, Trung Dung; Nagarajan, Neerajha

Cardiomyocytes show excitatory responses to stimulation solely by mechanical forces through their stretch-activated ion channels, and can fire action potentials upon mechanical stimulation through a pathway known as mechano-electric feedback. Furthermore, cardiomyocyte (CM) - cardiac fibroblasts (CF) can couple mechanically through cell-cell junctions. Here we investigated the effects of CM and CF mechanical coupling on myocardial physiology and pathology using a bio-nanoindentered coupled with fast calcium imaging and microelectrode arrays. In order to study mechanical signal transmission, we measured the contractile forces generated by CMs, as well as by CFs that were coupled to the CMs. We observed that CFs were beating with the same frequency but at smaller magnitude compared to CMs, and their contractility was dependent on the substrate stiffness. Our results showed that beating CMs actively stretched neighbouring CFs through the deformation of the substrate the cells were seeded on, which promoted the myocardial contractility through mechanical coupling. The results also revealed that CM contractility was propagated greater on soft substrates than stiff ones. Results of this study could help identify the role of the infarcted tissue stiffness and size on heart failure. This study is supported by NSF Grant No: 1530884.

Bi-sensory, striped representations: comparative insights from owl and platypus.

PubMed

Pettigrew, John D

2004-01-01

Bi-sensory striped arrays are described in owl and platypus that share some similarities with the other variant of bi-sensory striped array found in primate and carnivore striate cortex: ocular dominance columns. Like ocular dominance columns, the owl and platypus striped systems each involve two different topographic arrays that are cut into parallel stripes, and interdigitated, so that higher-order neurons can integrate across both arrays. Unlike ocular dominance stripes, which have a separate array for each eye, the striped array in the middle third of the owl tectum has a separate array for each cerebral hemisphere. Binocular neurons send outputs from both hemispheres to the striped array where they are segregated into parallel stripes according to hemisphere of origin. In platypus primary somatosensory cortex (S1), the two arrays of interdigitated stripes are derived from separate sensory systems in the bill, 40,000 electroreceptors and 60,000 mechanoreceptors. The stripes in platypus S1 cortex produce bimodal electrosensory-mechanosensory neurons with specificity for the time-of-arrival difference between the two systems. This "thunder-and-lightning" system would allow the platypus to estimate the distance of the prey using time disparities generated at the bill between the earlier electrical wave and the later mechanical wave caused by the motion of benthic prey. The functional significance of parallel, striped arrays is not clear, even for the highly-studied ocular dominance system, but a general strategy is proposed here that is based on the detection of temporal disparities between the two arrays that can be used to estimate distance.

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).

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

A High-Frequency Annular-Array Transducer Using an Interdigital Bonded 1-3 Composite

PubMed Central

Chabok, Hamid Reza; Cannata, Jonathan M.; Kim, Hyung Ham; Williams, Jay A.; Park, Jinhyoung; Shung, K. Kirk

2011-01-01

This paper reports the design, fabrication, and characterization of a 1–3 composite annular-array transducer. An interdigital bonded (IB) 1–3 composite was prepared using two IB operations on a fine-grain piezoelectric ceramic. The final composite had 19-μm-wide posts separated by 6-μm-wide polymer kerfs. A novel method to remove metal electrodes from polymer portions of the 1–3 composite was established to eliminate the need for patterning and aligning the electrode on the composite to the electrodes on a flexible circuit. Unloaded epoxy was used for both the matching and backing layers and a flexible circuit was used for interconnect. A prototype array was successfully fabricated and tested. The results were in reasonable agreement with those predicted by a circuit-analogous model. The average center frequency estimated from the measured pulse-echo responses of array elements was 33.5 MHz and the −6-dB fractional bandwidth was 57%. The average insertion loss recorded was 14.3 dB, and the maximum crosstalk between the nearest-neighbor elements was less than −37 dB. Images of a wire phantom and excised porcine eye were obtained to show the capabilities of the array for high-frequency ultrasound imaging. PMID:21244988

A high-frequency annular-array transducer using an interdigital bonded 1-3 composite.

PubMed

Chabok, Hamid Reza; Cannata, Jonathan M; Kim, Hyung Ham; Williams, Jay A; Park, Jinhyoung; Shung, K Kirk

2011-01-01

This paper reports the design, fabrication, and characterization of a 1-3 composite annular-array transducer. An interdigital bonded (IB) 1-3 composite was prepared using two IB operations on a fine-grain piezoelectric ceramic. The final composite had 19-μm-wide posts separated by 6-μm-wide polymer kerfs. A novel method to remove metal electrodes from polymer portions of the 1-3 composite was established to eliminate the need for patterning and aligning the electrode on the composite to the electrodes on a flexible circuit. Unloaded epoxy was used for both the matching and backing layers and a flexible circuit was used for interconnect. A prototype array was successfully fabricated and tested. The results were in reasonable agreement with those predicted by a circuit-analogous model. The average center frequency estimated from the measured pulse-echo responses of array elements was 33.5 MHz and the -6-dB fractional bandwidth was 57%. The average insertion loss recorded was 14.3 dB, and the maximum crosstalk between the nearest-neighbor elements was less than -37 dB. Images of a wire phantom and excised porcine eye were obtained to show the capabilities of the array for high-frequency ultrasound imaging.

AC electrokinetic drug delivery in dentistry using an interdigitated electrode assembly powered by inductive coupling.

PubMed

Ivanoff, Chris S; Wu, Jie Jayne; Mirzajani, Hadi; Cheng, Cheng; Yuan, Quan; Kevorkyan, Stepan; Gaydarova, Radostina; Tomlekova, Desislava

2016-10-01

AC electrokinetics (ACEK) has been shown to deliver certain drugs into human teeth more effectively than diffusion. However, using electrical wires to power intraoral ACEK devices poses risks to patients. The study demonstrates a novel interdigitated electrode arrays (IDE) assembly powered by inductive coupling to induce ACEK effects at appropriate frequencies to motivate drugs wirelessly. A signal generator produces the modulating signal, which multiplies with the carrier signal to produce the amplitude modulated (AM) signal. The AM signal goes through the inductive link to appear on the secondary coil, then rectified and filtered to dispose of its carrier signal, and the positive half of the modulating signal appears on the load. After characterizing the device, the device is validated under light microscopy by motivating carboxylate-modified microspheres, tetracycline, acetaminophen, benzocaine, lidocaine and carbamide peroxide particles with induced ACEK effects. The assembly is finally tested in a common dental bleaching application. After applying 35 % carbamide peroxide to human teeth topically or with the IDE at 1200 Hz, 5 Vpp for 20 min, spectrophotometric analysis showed that compared to diffusion, the IDE enhanced whitening in specular optic and specular optic excluded modes by 215 % and 194 % respectively. Carbamide peroxide absorbance by the ACEK group was two times greater than diffusion as measured by colorimetric oxidation-reduction and UV-Vis spectroscopy at 550 nm. The device motivates drugs of variable molecular weight and structure wirelessly. Wireless transport of drugs to intraoral targets under ACEK effects may potentially improve the efficacy and safety of drug delivery in dentistry.

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

NASA Astrophysics Data System (ADS)

Whalen, John J., III

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

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

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.

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

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

On-chip supercapacitors with ultrahigh volumetric performance based on electrochemically co-deposited CuO/polypyrrole nanosheet arrays

NASA Astrophysics Data System (ADS)

Qian, Tao; Zhou, Jinqiu; Xu, Na; Yang, Tingzhou; Shen, Xiaowei; Liu, Xuejun; Wu, Shishan; Yan, Chenglin

2015-10-01

We introduce a new method for fabricating unique on-chip supercapacitors based on CuO/polypyrrole core/shell nanosheet arrays by means of direct electrochemical co-deposition on interdigital-like electrodes. The prepared all-solid-state device demonstrates exceptionally high specific capacitance of 1275.5 F cm-3 (˜40 times larger than that of CuO-only supercapacitors) and high-energy-density of 28.35 mWh cm-3, which are both significantly greater than other solid-state supercapacitors. More importantly, the device maintains approximately 100% capacity retention at 2.5 A cm-3 after 3000 cycles. The in situ co-deposition of CuO/polypyrrole nanosheets on interdigital substrate enables effective charge transport, electrode fabrication integrity, and device integration. Because of their high energy, power density, and stable cycling stability, these newly developed on-chip supercapacitors permit fast, reliable applications in portable and miniaturized electronic devices.

On-chip supercapacitors with ultrahigh volumetric performance based on electrochemically co-deposited CuO/polypyrrole nanosheet arrays.

PubMed

Qian, Tao; Zhou, Jinqiu; Xu, Na; Yang, Tingzhou; Shen, Xiaowei; Liu, Xuejun; Wu, Shishan; Yan, Chenglin

2015-10-23

We introduce a new method for fabricating unique on-chip supercapacitors based on CuO/polypyrrole core/shell nanosheet arrays by means of direct electrochemical co-deposition on interdigital-like electrodes. The prepared all-solid-state device demonstrates exceptionally high specific capacitance of 1275.5 F cm(-3) (∼40 times larger than that of CuO-only supercapacitors) and high-energy-density of 28.35 mWh cm(-3), which are both significantly greater than other solid-state supercapacitors. More importantly, the device maintains approximately 100% capacity retention at 2.5 A cm(-3) after 3000 cycles. The in situ co-deposition of CuO/polypyrrole nanosheets on interdigital substrate enables effective charge transport, electrode fabrication integrity, and device integration. Because of their high energy, power density, and stable cycling stability, these newly developed on-chip supercapacitors permit fast, reliable applications in portable and miniaturized electronic devices.

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.

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.

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.

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

PubMed

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

2011-01-01

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

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.

Microfluidic device for the assembly and transport of microparticles

DOEpatents

James, Conrad D [Albuquerque, NM; Kumar, Anil [Framingham, MA; Khusid, Boris [New Providence, NJ; Acrivos, Andreas [Stanford, CA

2010-06-29

A microfluidic device comprising independently addressable arrays of interdigitated electrodes can be used to assembly and transport large-scale microparticle structures. The device and method uses collective phenomena in a negatively polarized suspension exposed to a high-gradient strong ac electric field to assemble the particles into predetermined locations and then transport them collectively to a work area for final assembly by sequentially energizing the electrode arrays.

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...

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

Expression of Fas, FasL, caspase-8 and other factors of the extrinsic apoptotic pathway during the onset of interdigital tissue elimination.

PubMed

Svandova, E Budisova; Vesela, B; Lesot, H; Poliard, A; Matalova, E

2017-04-01

Elimination of the interdigital web is considered to be the classical model for assessing apoptosis. So far, most of the molecules described in the process have been connected to the intrinsic (mitochondrial) pathway. The extrinsic (receptor mediated) apoptotic pathway has been rather neglected, although it is important in development, immunomodulation and cancer therapy. This work aimed to investigate factors of the extrinsic apoptotic machinery during interdigital regression with a focus on three crucial initiators: Fas, Fas ligand and caspase-8. Immunofluorescent analysis of mouse forelimb histological sections revealed abundant expression of these molecules prior to digit separation. Subsequent PCR Array analyses indicated the expression of several markers engaged in the extrinsic pathway. Between embryonic days 11 and 13, statistically significant increases in the expression of Fas and caspase-8 were observed, along with other molecules involved in the extrinsic apoptotic pathway such as Dapk1, Traf3, Tnsf12, Tnfrsf1A and Ripk1. These results demonstrate for the first time the presence of extrinsic apoptotic components in mouse limb development and indicate novel candidates in the molecular network accompanying the regression of interdigital tissue during digitalisation.

Stopband-Extended and Size-Miniaturized Low-Pass Filter Based on Interdigital Capacitor Loaded Hairpin Resonator with Four Transmission Zeros

NASA Astrophysics Data System (ADS)

Wu, Jia-Jia; Li, Lin

2018-04-01

In this paper, a compact low-pass filter (LPF) with wide stopband is proposed based on interdigital capacitor loaded hairpin resonator. The structure composed of an upper high-impedance transmission line, a middle interdigital capacitor, and a pair of inter-coupled symmetrical stepped-impedance stubs. Detailed investigation into this structure based on even-odd mode approach reveals that up to four transmission zeros can be generated and reallocated by choosing the proper circuit parameters. And owing to the aid of transmission zeros, the fabricated quasi-elliptic LPFs experimentally demonstrate a wide 20dB stopband from 1.4fc to 5.1fc using a compact size of only 0.005 λg2.

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.

Electrochemical Impedance Immunosensor Based on Self-Assembled Monolayers for Rapid Detection of Escherichia coli O157:H7 with Signal Amplification Using Lectin

PubMed Central

Li, Zhanming; Fu, Yingchun; Fang, Weihuan; Li, Yanbin

2015-01-01

Escherichia coli O157:H7 is a predominant foodborne pathogen with severe pathogenicity, leading to increasing attention given to rapid and sensitive detection. Herein, we propose an impedance biosensor using new kinds of screen-printed interdigitated microelectrodes (SPIMs) and wheat germ agglutinin (WGA) for signal amplification to detect E. coli O157:H7 with high sensitivity and time-efficiency. The SPIMs integrate the high sensitivity and short response time of the interdigitated electrodes and the low cost of the screen-printed electrodes. Self-assembling of bi-functional 3-dithiobis-(sulfosuccinimidyl-propionate) (DTSP) on the SPIMs was investigated and was proved to be able to improve adsorption quantity and stability of biomaterials. WGA was further adopted to enhance the signal taking advantage of the abundant lectin-binding sites on the bacteria surface. The immunosensor exhibited a detection limit of 102 cfu·mL−1, with a linear detection range from 102 to 107 cfu·mL−1 (r2 = 0.98). The total detection time was less than 1 h, showing its comparable sensitivity and rapid response. Furthermore, the low cost of one SPIM significantly reduced the detection cost of the biosensor. The biosensor may have great promise in food safety analysis and lead to a portable biosensing system for routine monitoring of foodborne pathogens. PMID:26251911

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

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.

Aeroelastic Analysis of Helicopter Rotor Blades Incorporating Anisotropic Piezoelectric Twist Actuation

NASA Technical Reports Server (NTRS)

Wilkie, W. Keats; Belvin, W. Keith; Park, K. C.

1996-01-01

A simple aeroelastic analysis of a helicopter rotor blade incorporating embedded piezoelectric fiber composite, interdigitated electrode blade twist actuators is described. The analysis consists of a linear torsion and flapwise bending model coupled with a nonlinear ONERA based unsteady aerodynamics model. A modified Galerkin procedure is performed upon the rotor blade partial differential equations of motion to develop a system of ordinary differential equations suitable for dynamics simulation using numerical integration. The twist actuation responses for three conceptual fullscale blade designs with realistic constraints on blade mass are numerically evaluated using the analysis. Numerical results indicate that useful amplitudes of nonresonant elastic twist, on the order of one to two degrees, are achievable under one-g hovering flight conditions for interdigitated electrode poling configurations. Twist actuation for the interdigitated electrode blades is also compared with the twist actuation of a conventionally poled piezoelectric fiber composite blade. Elastic twist produced using the interdigitated electrode actuators was found to be four to five times larger than that obtained with the conventionally poled actuators.

An aeroelastic analysis of helicopter rotor blades incorporating piezoelectric fiber composite twist actuation

NASA Technical Reports Server (NTRS)

Wilkie, W. Keats; Park, K. C.

1996-01-01

A simple aeroelastic analysis of a helicopter rotor blade incorporating embedded piezoelectric fiber composite, interdigitated electrode blade twist actuators is described. The analysis consist of a linear torsion and flapwise bending model coupled with a nonlinear ONERA based unsteady aerodynamics model. A modified Galerkin procedure is performed upon the rotor blade partial differential equations of motion to develop a system of ordinary differential equations suitable for numerical integration. The twist actuation responses for three conceptual full-scale blade designs with realistic constraints on blade mass are numerically evaluated using the analysis. Numerical results indicate that useful amplitudes of nonresonant elastic twist, on the order of one to two degrees, are achievable under one-g hovering flight conditions for interdigitated electrode poling configurations. Twist actuation for the interdigitated electrode blades is also compared with the twist actuation of a conventionally poled piezoelectric fiber composite blade. Elastic twist produced using the interdigitated electrode actuators was found to be four to five times larger than that obtained with the conventionally poled actuators.

Microelectrode voltammetry of multi-electron transfers complicated by coupled chemical equilibria: a general theory for the extended square scheme.

PubMed

Laborda, Eduardo; Gómez-Gil, José María; Molina, Angela

2017-06-28

A very general and simple theoretical solution is presented for the current-potential-time response of reversible multi-electron transfer processes complicated by homogeneous chemical equilibria (the so-called extended square scheme). The expressions presented here are applicable regardless of the number of electrons transferred and coupled chemical processes, and they are particularized for a wide variety of microelectrode geometries. The voltammetric response of very different systems presenting multi-electron transfers is considered for the most widely-used techniques (namely, cyclic voltammetry, square wave voltammetry, differential pulse voltammetry and steady state voltammetry), studying the influence of the microelectrode geometry and the number and thermodynamics of the (electro)chemical steps. Most appropriate techniques and procedures for the determination of the 'interaction' between successive transfers are discussed. Special attention is paid to those situations where homogeneous chemical processes, such as protonation, complexation or ion association, affect the electrochemical behaviour of the system by different stabilization of the oxidation states.

Study of Electrochemical Reactions Using Nanospray Desorption Electrospray Ionization Mass Spectrometry

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

Liu, Pengyuan; Lanekoff, Ingela T.; Laskin, Julia

2012-07-03

The combination of electrochemistry (EC) and mass spectrometry (MS) is a powerful analytical tool for studying mechanisms of redox reactions, identification of products and intermediates, and online derivatization/recognition of analytes. This work reports a new coupling interface for EC/MS by employing nanospray desorption electrospray ionization (nano-DESI), a recently developed ambient ionization method. We demonstrate online coupling of nano-DESI-MS with a traditional electrochemical flow cell, in which the electrolyzed solution emanating from the cell is ionized by nano-DESI for MS analysis. Furthermore, we show first coupling of nano-DESI-MS with an interdigitated array (IDA) electrode enabling chemical analysis of electrolyzed samples directlymore » from electrode surfaces. Because of its inherent sensitivity, nano-DESI enables chemical analysis of small volumes and concentrations of sample solution. Specifically, good-quality signal of dopamine and its oxidized form, dopamine ortho-quinone, was obtained using 10 μL of 1 μM solution of dopamine on the IDA. Oxidation of dopamine, reduction of benzodiazepines, and electrochemical derivatization of thiol groups were used to demonstrate the performance of the technique. Our results show the potential of nano-DESI as a novel interface for electrochemical mass spectrometry research.« less

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

Cavity transport effects in generator-collector electrochemical analysis of nitrobenzene.

PubMed

Lewis, Grace E M; Dale, Sara E C; Kasprzyk-Hordern, Barbara; Lubben, Anneke T; Barnes, Edward O; Compton, Richard G; Marken, Frank

2014-09-21

Two types of generator-collector electrode systems, (i) a gold-gold interdigitated microband array and (ii) a gold-gold dual-plate microtrench, are compared for nitrobenzene electroanalysis in aerated aqueous 0.1 M NaOH. The complexity of the nitrobenzene reduction in conjunction with the presence of ambient levels of oxygen in the analysis solution provide a challenging problem in which feedback-amplified generator-collector steady state currents provide the analytical signal. In contrast to the more openly accessible geometry of the interdigitated array electrode, where the voltammetric response for nitrobenzene is less well-defined and signals drift, the voltammetric response for the cavity-like microtrench electrode is stable and readily detectable at 1 μM level. Both types of electrode show oxygen-enhanced low concentration collector current responses due to additional feedback via reaction intermediates. The observations are rationalised in terms of a "cavity transport coefficient" which is beneficial in the dual-plate microtrench, where oxygen interference effects are suppressed and the analytical signal is amplified and stabilised.

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...

High frequency GaAlAs modulator and photodetector for phased array antenna applications

NASA Technical Reports Server (NTRS)

Claspy, P. C.; Chorey, C. M.; Hill, S. M.; Bhasin, K. B.

1988-01-01

A waveguide Mach-Zehnder electro-optic modulator and an interdigitated photoconductive detector designed to operate at 820 nm, fabricated on different GaAlAs/GaAs heterostructure materials, are being investigated for use in optical interconnects in phased array antenna systems. Measured optical attenuation effects in the modulator are discussed and the observed modulation performance up to 1 GHz is presented. Measurements of detector frequency response are described and results presented.

Thermally Induced Lateral Motion of α-Zirconium Phosphate Layers Intercalated with Hexadecylamines

NASA Astrophysics Data System (ADS)

Char, Kookheon

2005-03-01

Well-defined intercalated structure, either interdigitated layers or bilayers, of hexadecylamines (HDAs) in a confined space of a highly-functionalized layered material, α- zirconium phosphate (α-ZrP), was prepared and these two distinct intercalated structures can serve as model systems to investigate the interaction of the two monolayers whose amphiphilic tails are adjacent to each other. Acidic functional groups (-POH) on the α-ZrP are in well-ordered array and the number of functional group is quite high (i.e., cationic exchange capacity (CEC) = 664 mmole/100 g, area per one charge site = 0.24 nm^2) enough to realize the bilayers (i.e., discrete two monolayers) of HDAs within the α-ZrP interlayer. We employed the two-step intercalation mechanism for the preparation of well- ordered interdigitated layers as well as the bilayers of alkyl chains attached to both sides of the α-ZrP intergallery. An intriguing lateral motion of the α-ZrP sheets was observed with in-situ SAXS measurements for the interdigitated layer during heating and cooling cycle and verified with TEM. This lateral motion is believed to be due to the transition from the tilted to the untilted conformation of the interdigitated HDA chains and this transition is found to be thermally reversible.

Direct quantification of test bacteria in synthetic water-polluted samples by square wave voltammetry and chemometric methods.

PubMed

Carpani, Irene; Conti, Paolo; Lanteri, Silvia; Legnani, Pier Paolo; Leoni, Erica; Tonelli, Domenica

2008-02-28

A home-made microelectrode array, based on reticulated vitreous carbon, was used as working electrode in square wave voltammetry experiments to quantify the bacterial load of Escherichia coli ATCC 13706 and Pseudomonas aeruginosa ATCC 27853, chosen as test microorganisms, in synthetic samples similar to drinking water (phosphate buffer). Raw electrochemical signals were analysed with partial least squares regression coupled to variable selection in order to correlate these values with the bacterial load estimated by aerobic plate counting. The results demonstrated the ability of the method to detect even low loads of microorganisms in synthetic water samples. In particular, the model detects the bacterial load in the range 3-2,020 CFU ml(-1) for E. coli and in the range 76-155,556 CFU ml(-1) for P. aeruginosa.

3D Printing of Carbon Nanotubes-Based Microsupercapacitors.

PubMed

Yu, Wei; Zhou, Han; Li, Ben Q; Ding, Shujiang

2017-02-08

A novel 3D printing procedure is presented for fabricating carbon-nanotubes (CNTs)-based microsupercapacitors. The 3D printer uses a CNTs ink slurry with a moderate solid content and prints a stream of continuous droplets. Appropriate control of a heated base is applied to facilitate the solvent removal and adhesion between printed layers and to improve the structure integrity without structure delamination or distortion upon drying. The 3D-printed electrodes for microsupercapacitors are characterized by SEM, laser scanning confocal microscope, and step profiler. Effect of process parameters on 3D printing is also studied. The final solid-state microsupercapacitors are assembled with the printed multilayer CNTs structures and poly(vinyl alcohol)-H 3 PO 4 gel as the interdigitated microelectrodes and electrolyte. The electrochemical performance of 3D printed microsupercapacitors is also tested, showing a significant areal capacitance and excellent cycle stability.

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

Nanostructured cavity devices for extracellular stimulation of HL-1 cells

NASA Astrophysics Data System (ADS)

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

2015-05-01

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

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.

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.

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.

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.

Label-free capacitive biosensor for sensitive detection of multiple biomarkers using gold interdigitated capacitor arrays.

PubMed

Qureshi, Anjum; Niazi, Javed H; Kallempudi, Saravan; Gurbuz, Yasar

2010-06-15

In this study, a highly sensitive and label-free multianalyte capacitive immunosensor was developed based on gold interdigitated electrodes (GID) capacitor arrays to detect a panel of disease biomarkers. C-reactive protein (CRP), TNFalpha, and IL6 have strong and consistent relationships between markers of inflammation and future cardiovascular risk (CVR) events. Early detection of a panel of biomarkers for a disease could enable accurate prediction of a disease risk. The detection of protein biomarkers was based on relative change in capacitive/dielectric properties. Two different lab-on-a-chip formats were employed for multiple biomarker detection on GID-capacitors. In format I, capacitor arrays were immobilized with pure forms of anti-CRP, -TNFalpha, and -IL6 antibodies in which each capacitor array contained a different immobilized antibody. Here, the CRP and IL6 were detected in the range 25 pg/ml to 25 ng/ml and 25 pg/ml to 1 ng/ml for TNFalpha in format I. Sensitive detection was achieved with chips co-immobilized (diluted) with equimolar mixtures of anti-CRP, -IL6, and -TNFalpha antibodies (format II) in which all capacitors in an array were identical and tested for biomarkers with sequential incubation. The resulting response to CRP, IL6, and TNFalpha in format II for all biomarkers was found to be within 25 pg/ml to 25 ng/ml range. The capacitive biosensor for panels of inflammation and CVR markers show significant clinical value and provide great potential for detection of biomarker panel in suspected subjects for early diagnosis. Copyright 2010 Elsevier B.V. All rights reserved.

SAW Synthesis With IDTs Array and the Inverse Filter: Toward a Versatile SAW Toolbox for Microfluidics and Biological Applications.

PubMed

Riaud, Antoine; Baudoin, Michael; Thomas, Jean-Louis; Bou Matar, Olivier

2016-10-01

Surface acoustic waves (SAWs) are versatile tools to manipulate fluids at small scales for microfluidics and biological applications. A nonexhaustive list of operations that can be performed with SAW includes sessile droplet displacement, atomization, division, and merging but also the actuation of fluids embedded in microchannels or the manipulation of suspended particles. However, each of these operations requires a specific design of the wave generation system, the so-called interdigitated transducers (IDTs). Depending on the application, it might indeed be necessary to generate focused or plane, propagating or standing, and aligned or shifted waves. Furthermore, the possibilities offered by more complex wave fields such as acoustical vortices for particle tweezing and liquid twisting cannot be explored with classical IDTs. In this paper, we show that the inverse filter technique coupled with an IDTs array enables us to synthesize all classical wave fields used in microfluidics and biological applications with a single multifunctional platform. It also enables us to generate swirling SAWs, whose potential for the on-chip synthesis of tailored acoustical vortices has been demonstrated lately. The possibilities offered by this platform are illustrated by performing many operations successively on sessile droplets with the same system.

Template method for fabricating interdigitate p-n heterojunction for organic solar cell

PubMed Central

2012-01-01

Anodic aluminum oxide (AAO) templates are used to fabricate arrays of poly(3-hexylthiophene) (P3HT) pillars. This technique makes it possible to control the dimensions of the pillars, namely their diameters, intervals, and heights, on a tens-of-nanometer scale. These features are essential for enhancing carrier processes such as carrier generation, exciton diffusion, and carrier dissociation and transport. An interdigitated p-n junction between P3HT pillars and fullerene (C60) exhibits a photovoltaic effect. Although the device properties are still preliminary, the experimental results indicate that an AAO template is an effective tool with which to develop organic solar cells because highly regulated nanostructures can be produced on large areas exceeding 100 mm2. PMID:22908897

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.

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

PubMed

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

2015-10-15

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

Time of Flight Electrochemistry: Diffusion Coefficient Measurements Using Interdigitated Array (IDA) Electrodes

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

Liu, Fei; Kolesov, Grigory; Parkinson, Bruce A.

2014-09-26

A simple and straightforward method for measuring diffusion coefficients using interdigitated array (IDA) electrodes is reported. The method does not require that the exact electrode area be known but depends only the size of the gap between the IDA electrode pairs. Electroactive molecules produced at the generator electrode of the IDA by a voltage step or scan can diffuse to the collector electrode and the time delay before the current for the reverse electrochemical reaction is detected at the collector is used to calculate the diffusion coefficient. The measurement of the diffusion rate of Ru(NH3)6+2 in aqueous solution has beenmore » used as an example measuring diffusion coefficients using this method. Additionally, a digital simulation of the electrochemical response of the IDA electrodes was used to simulate the entire current/voltage/time behavior of the system and verify the experimentally measured diffusion coefficients. This work was supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the Department of Energy, Office of Science, Office of Basic Energy Sciences.« less

Direct protein detection with a nano-interdigitated array gate MOSFET.

PubMed

Tang, Xiaohui; Jonas, Alain M; Nysten, Bernard; Demoustier-Champagne, Sophie; Blondeau, Franoise; Prévot, Pierre-Paul; Pampin, Rémi; Godfroid, Edmond; Iñiguez, Benjamin; Colinge, Jean-Pierre; Raskin, Jean-Pierre; Flandre, Denis; Bayot, Vincent

2009-08-15

A new protein sensor is demonstrated by replacing the gate of a metal oxide semiconductor field effect transistor (MOSFET) with a nano-interdigitated array (nIDA). The sensor is able to detect the binding reaction of a typical antibody Ixodes ricinus immunosuppressor (anti-Iris) protein at a concentration lower than 1 ng/ml. The sensor exhibits a high selectivity and reproducible specific detection. We provide a simple model that describes the behavior of the sensor and explains the origin of its high sensitivity. The simulated and experimental results indicate that the drain current of nIDA-gate MOSFET sensor is significantly increased with the successive binding of the thiol layer, Iris and anti-Iris protein layers. It is found that the sensor detection limit can be improved by well optimizing the geometrical parameters of nIDA-gate MOSFET. This nanobiosensor, with real-time and label-free capabilities, can easily be used for the detection of other proteins, DNA, virus and cancer markers. Moreover, an on-chip associated electronics nearby the sensor can be integrated since its fabrication is compatible with complementary metal oxide semiconductor (CMOS) technology.

Preparation, applications, and digital simulation of carbon interdigitated array electrodes.

PubMed

Liu, Fei; Kolesov, Grigory; Parkinson, B A

2014-08-05

Carbon interdigitated array (IDA) electrodes with features sizes down to 1.2 μm were fabricated by controlled pyrolysis of patterned photoresist. Cyclic voltammetry of reversible redox species produced the expected steady-state currents. The collection efficiency depends on the IDA electrode spacing, which ranged from around 2.7 to 16.5 μm, with the smaller dimensions achieving higher collection efficiencies of up to 98%. The signal amplification because of redox cycling makes it possible to detect species at relatively low concentrations (10(-5) molar) and the small spacing allows detection of transient electrogenerated species with much shorter lifetimes (submillisecond). Digital simulation software that accounts for both the width and height of electrode elements as well as the electrode spacing was developed to model the IDA electrode response. The simulations are in quantitative agreement with experimental data for both a simple fast one electron redox reaction and an electron transfer with a following chemical reaction at the IDAs with larger gaps whereas currents measured for the smallest IDA electrodes, that were larger than the simulated currents, are attributed to convection from induced charge electrokinetic flow.

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.

A High-Frequency Linear Ultrasonic Array Utilizing an Interdigitally Bonded 2-2 Piezo-Composite

PubMed Central

Cannata, Jonathan M.; Williams, Jay A.; Zhang, Lequan; Hu, Chang-Hong; Shung, K. Kirk

2011-01-01

This paper describes the development of a high-frequency 256-element linear ultrasonic array utilizing an interdigitally bonded (IB) piezo-composite. Several IB composites were fabricated with different commercial and experimental piezoelectric ceramics and evaluated to determine a suitable formulation for use in high-frequency linear arrays. It was found that the fabricated fine-scale 2–2 IB composites outperformed 1–3 IB composites with identical pillar- and kerf-widths. This result was not expected and lead to the conclusion that dicing damage was likely the cause of the discrepancy. Ultimately, a 2–2 composite fabricated using a fine-grain piezoelectric ceramic was chosen for the array. The composite was manufactured using one IB operation in the azimuth direction to produce approximately 19-μm-wide pillars separated by 6-μm-wide kerfs. The array had a 50 μm (one wavelength in water) azimuth pitch, two matching layers, and 2 mm elevation length focused to 7.3 mm using a polymethylpentene (TPX) lens. The measured pulse-echo center frequency for a representative array element was 28 MHz and −6-dB band-width was 61%. The measured single-element transmit −6-dB directivity was estimated to be 50°. The measured insertion loss was 19 dB after compensating for the effects of attenuation and diffraction in the water bath. A fine-wire phantom was used to assess the lateral and axial resolution of the array when paired with a prototype system utilizing a 64-channel analog beamformer. The −6-dB lateral and axial resolutions were estimated to be 125 and 68 μm, respectively. An anechoic cyst phantom was also imaged to determine the minimum detectable spherical inclusion, and thus the 3-D resolution of the array and beamformer. The minimum anechoic cyst detected was approximately 300 μm in diameter. PMID:21989884

Monte Carlo Modeling of VLWIR HgCdTe Interdigitated Pixel Response

NASA Astrophysics Data System (ADS)

D'Souza, A. I.; Stapelbroek, M. G.; Wijewarnasuriya, P. S.

2010-07-01

Increasing very long-wave infrared (VLWIR, λ c ≈ 15 μm) pixel operability was approached by subdividing each pixel into four interdigitated subpixels. High response is maintained across the pixel, even if one or two interdigitated subpixels are deselected (turned off), because interdigitation provides that the preponderance of minority carriers photogenerated in the pixel are collected by the selected subpixels. Monte Carlo modeling of the photoresponse of the interdigitated subpixel simulates minority-carrier diffusion from carrier creation to recombination. Each carrier generated at an appropriately weighted random location is assigned an exponentially distributed random lifetime τ i, where < τ i> is the bulk minority-carrier lifetime. The minority carrier is allowed to diffuse for a short time d τ, and the fate of the carrier is decided from its present position and the boundary conditions, i.e., whether the carrier is absorbed in a junction, recombined at a surface, reflected from a surface, or recombined in the bulk because it lived for its designated lifetime. If nothing happens, the process is then repeated until one of the boundary conditions is attained. The next step is to go on to the next carrier and repeat the procedure for all the launches of minority carriers. For each minority carrier launched, the original location and boundary condition at fatality are recorded. An example of the results from Monte Carlo modeling is that, for a 20- μm diffusion length, the calculated quantum efficiency (QE) changed from 85% with no subpixels deselected, to 78% with one subpixel deselected, 67% with two subpixels deselected, and 48% with three subpixels deselected. Demonstration of the interdigitated pixel concept and verification of the Monte Carlo modeling utilized λ c(60 K) ≈ 15 μm HgCdTe pixels in a 96 × 96 array format. The measured collection efficiency for one, two, and three subelements selected, divided by the collection efficiency for all four subelements selected, matched that calculated using Monte Carlo modeling.

Auxiliary Components for Kilopixel Transition Edge Sensor Arrays

NASA Technical Reports Server (NTRS)

Brown, Ari-David; Chervenak, James A.; Chuss, David; Hilton Gene C.; Mikula, Vilem; Henry, ROss; Wollack, Edward; Zhao, Yue

2007-01-01

We have fabricated transition edge sensor bolometer focal plane arrays sensitive to mm-submillimeter (0.1-3 THz) radiation for the Atacama Cosmology Telescope (ACT), which will probe the cosmic microwave background at 0.147,0.215, and 0.279 GHz. Central to the performance of these bolometers is a set of auxiliary resistive components. Here we discuss shunt resistors, which allow for tight optimization of bolometer time constant and sensitivity. Our shunt resistors consist of AuPd strips grown atop of interdigitated superconducting MoN, wires. We can tailor the shunt resistance by altering the dimensions of the AuPd strips and the pitch and width of the MoN, wires and can fabricate over 1000 shunts on a single 4" wafer. By modeling the resistance dependence of these parameters, a variety of different 0.77 +I-0.13 mOhm shunt resistors have been fabricated. This variety includes different shunts possessing MoN, wires with wire width equal to 1.5 and 10 microns and pitch equal to 4.5 and 26 microns, respectively. Our ability to set the resistance of the shunts hints at the scalability of our design. We have also integrated a Si02 capping layer into our shunt resistor fabrication scheme, which inhibits metal corrosion and eventual degradation of the shunt. Consequently, their robustness coupled with their high packing density makes these resistive components attractive for future kilopixel detector arrays.

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

Soft chitosan microbeads scaffold for 3D functional neuronal networks.

PubMed

Tedesco, Maria Teresa; Di Lisa, Donatella; Massobrio, Paolo; Colistra, Nicolò; Pesce, Mattia; Catelani, Tiziano; Dellacasa, Elena; Raiteri, Roberto; Martinoia, Sergio; Pastorino, Laura

2018-02-01

The availability of 3D biomimetic in vitro neuronal networks of mammalian neurons represents a pivotal step for the development of brain-on-a-chip experimental models to study neuronal (dys)functions and particularly neuronal connectivity. The use of hydrogel-based scaffolds for 3D cell cultures has been extensively studied in the last years. However, limited work on biomimetic 3D neuronal cultures has been carried out to date. In this respect, here we investigated the use of a widely popular polysaccharide, chitosan (CHI), for the fabrication of a microbead based 3D scaffold to be coupled to primary neuronal cells. CHI microbeads were characterized by optical and atomic force microscopies. The cell/scaffold interaction was deeply characterized by transmission electron microscopy and by immunocytochemistry using confocal microscopy. Finally, a preliminary electrophysiological characterization by micro-electrode arrays was carried out. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-01-31

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

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...

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

Polymer-based sensor array for phytochemical detection

NASA Astrophysics Data System (ADS)

Weerakoon, Kanchana A.; Hiremath, Nitilaksha; Chin, Bryan A.

2012-05-01

Monitoring for the appearance of volatile organic compounds emitted by plants which correspond to time of first insect attack can be used to detect the early stages of insect infestation. This paper reports a chemical sensor array consisting of polymer based chemiresistor sensors that could detect insect infestation effectively. The sensor array consists of sensors with micro electronically fabricated interdigitated electrodes, and twelve different types of electro active polymer layers. The sensor array was cheap, easy to fabricate, and could be used easily in agricultural fields. The polymer array was found to be sensitive to a variety of volatile organic compounds emitted by plants including γ-terpinene α-pinene, pcymene, farnesene, limonene and cis-hexenyl acetate. The sensor array was not only able to detect but also distinguish between these compounds. The twelve sensors produced a resistance change for each of the analytes detected, and each of these responses together produced a unique fingerprint, enabling to distinguish among these chemicals.

Carbon Nanotube Electrode Arrays For Enhanced Chemical and Biological Sensing

NASA Technical Reports Server (NTRS)

Han, Jie

2003-01-01

Applications of carbon nanotubes for ultra-sensitive electrical sensing of chemical and biological species have been a major focus in NASA Ames Center for Nanotechnology. Great progress has been made toward controlled growth and chemical functionalization of vertically aligned carbon nanotube arrays and integration into micro-fabricated chip devices. Carbon nanotube electrode arrays devices have been used for sub-attomole detection of DNA molecules. Interdigitated carbon nanotubes arrays devices have been applied to sub ppb (part per billion) level chemical sensing for many molecules at room temperature. Stability and reliability have also been addressed in our device development. These results show order of magnitude improvement in device performance, size and power consumption as compared to micro devices, promising applications of carbon nanotube electrode arrays for clinical molecular diagnostics, personal medical testing and monitoring, and environmental monitoring.

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

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.

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

Manganese oxide micro-supercapacitors with ultra-high areal capacitance

NASA Astrophysics Data System (ADS)

Wang, Xu; Myers, Benjamin D.; Yan, Jian; Shekhawat, Gajendra; Dravid, Vinayak; Lee, Pooi See

2013-05-01

A symmetric micro-supercapacitor is constructed by electrochemically depositing manganese oxide onto micro-patterned current collectors. High surface-to-volume ratio of manganese oxide and short diffusion distance between electrodes give an ultra-high areal capacitance of 56.3 mF cm-2 at a current density of 27.2 μA cm-2.A symmetric micro-supercapacitor is constructed by electrochemically depositing manganese oxide onto micro-patterned current collectors. High surface-to-volume ratio of manganese oxide and short diffusion distance between electrodes give an ultra-high areal capacitance of 56.3 mF cm-2 at a current density of 27.2 μA cm-2. Electronic supplementary information (ESI) available: Experimental procedures; optical images of micro-supercapacitors; areal capacitances of samples M-0.3C, M-0.6C and M-0.9C; illustration of interdigital finger electrodes; Nyquist plot of Co(OH)2 deposited on micro-electrodes. See DOI: 10.1039/c3nr00210a

An Enhanced Platform to Analyse Low-Affinity Amyloid β Protein by Integration of Electrical Detection and Preconcentrator.

PubMed

Yoo, Yong Kyoung; Yoon, Dae Sung; Kim, Gangeun; Kim, Jinsik; Han, Sung Il; Lee, Junwoo; Chae, Myung-Sic; Lee, Sang-Myung; Lee, Kyu Hyoung; Hwang, Kyo Seon; Lee, Jeong Hoon

2017-10-30

Sensitivity and limit of detection (LOD) enhancement are essential criteria for the development of ultrasensitive molecular sensors. Although various sensor types have been investigated to enhance sensitivity and LOD, analyte detection and its quantification are still challenging, particularly for protein-protein interactions with low association constants. To solve this problem, here, we used ion concentration polarization (ICP)-based preconcentration to increase the local concentration of analytes in a microfluidic platform for LOD improvement. This was the first demonstration of a microfluidic device with an integrated ICP preconcentrator and interdigitated microelectrode (IME) sensor to detect small changes in surface binding between antigens and antibodies. We detected the amyloid beta (Aβ) protein, an Alzheimer's disease marker, with low binding affinity to its antibodies by adopting ICP preconcentration phenomena. We demonstrated that a combination of ICP preconcentrator and IME sensor increased the LOD by 13.8-fold to femtomolar level (8.15 fM), which corresponds to a significant advance for clinical applications.

A new design of a miniature filter on microstrip resonators with an interdigital structure of conductors

NASA Astrophysics Data System (ADS)

Belyaev, B. A.; Serzhantov, A. M.; Bal'va, Ya. F.; Leksikov, An. A.; Galeev, R. G.

2015-05-01

A microstrip bandpass filter of new design based on original resonators with an interdigital structure of conductors has been studied. The proposed filters of third to sixth order are distinguished for their high frequency-selective properties and much smaller size than analogs. It is established that a broad stop band, extending up to a sixfold central bandpass frequency, is determined by low unloaded Q of higher resonance mode and weak coupling of resonators in the pass band. It is shown for the first time that, as the spacing of interdigital stripe conductors decreases, the Q of higher resonance mode monotonically drops, while the Q value for the first operating mode remains high. A prototype fourth-order filter with a central frequency of 0.9 GHz manufactured on a ceramic substrate with dielectric permittivity ɛ = 80 has microstrip topology dimensions of 9.5 × 4.6 × 1 mm3. The electrodynamic 3D model simulations of the filter characteristics agree well with the results of measurements.

Electrochemical Visualization of Intracellular Hydrogen Peroxide at Single Cells.

PubMed

He, Ruiqin; Tang, Huifen; Jiang, Dechen; Chen, Hong-yuan

2016-02-16

In this Letter, the electrochemical visualization of hydrogen peroxide inside one cell was achieved first using a comprehensive Au-luminol-microelectrode and electrochemiluminescence. The capillary with a tip opening of 1-2 μm was filled with the mixture of chitosan and luminol, which was coated with the thin layers of polyvinyl chloride/nitrophenyloctyl ether (PVC/NPOE) and gold as the microelectrode. Upon contact with the aqueous hydrogen peroxide, hydrogen peroxide and luminol in contact with the gold layer were oxidized under the positive potential resulting in luminescence for the imaging. Due to the small diameter of the electrode, the microelectrode tip was inserted into one cell and the bright luminescence observed at the tip confirmed the visualization of intracellular hydrogen peroxide. The further coupling of oxidase on the electrode surface could open the field in the electrochemical imaging of intracellular biomolecules at single cells, which benefited the single cell electrochemical detection.

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

Nanoscale coupling of photons to vibrational excitation of Ag nanoparticle 2D array studied by scanning tunneling microscope light emission spectroscopy.

PubMed

Katano, Satoshi; Toma, Koji; Toma, Mana; Tamada, Kaoru; Uehara, Yoichi

2010-11-28

Scanning tunneling microscope light emission (STM-LE) spectroscopy has been utilized to elucidate the luminescence phenomena of Ag nanoparticles capped with myristate (myristate-capped AgNP) and 2-methyl-1-propanethiolate (C(4)S-capped AgNP) on the dodecanethiol-precovered Au substrate. The STM imaging revealed that myristate-capped AgNPs form an ordered hexagonal array whereas C(4)S-capped AgNPs show imperfect ordering, indicating that a shorter alkyl chain of C(4)S-capped AgNP is not sufficient to form rigid interdigitation. It should be noted that such a nanoparticle ordering affects the luminescence properties of the Ag nanoparticle. We found that the STM-LE is only detected from the Ag nanoparticles forming the two-dimensional superlattice. This indicates that the STM-LE of the Ag nanoparticle is radiated via the collective excitation of the local surface plasmon resonance (LSPR) spread over the Ag nanoparticles. Note that the STM-LE spectra of the Ag nanoparticles exhibit spike-like peaks superimposed on the broad light emission peak. Using Raman spectroscopy, we concluded that the spike-like structure appearing in the STM-LE spectra is associated with the vibrational excitation of the molecule embedded between Ag nanoparticles.

Patterned optogenetic modulation of neurovascular and metabolic signals

PubMed Central

Richner, Thomas J; Baumgartner, Ryan; Brodnick, Sarah K; Azimipour, Mehdi; Krugner-Higby, Lisa A; Eliceiri, Kevin W; Williams, Justin C; Pashaie, Ramin

2015-01-01

The hemodynamic and metabolic response of the cortex depends spatially and temporally on the activity of multiple cell types. Optogenetics enables specific cell types to be modulated with high temporal precision and is therefore an emerging method for studying neurovascular and neurometabolic coupling. Going beyond temporal investigations, we developed a microprojection system to apply spatial photostimulus patterns in vivo. We monitored vascular and metabolic fluorescence signals after photostimulation in Thy1-channelrhodopsin-2 mice. Cerebral arteries increased in diameter rapidly after photostimulation, while nearby veins showed a slower smaller response. The amplitude of the arterial response was depended on the area of cortex stimulated. The fluorescence signal emitted at 450/100 nm and excited with ultraviolet is indicative of reduced nicotinamide adenine dinucleotide, an endogenous fluorescent enzyme involved in glycolysis and the citric acid cycle. This fluorescence signal decreased quickly and transiently after optogenetic stimulation, suggesting that glucose metabolism is tightly locked to optogenetic stimulation. To verify optogenetic stimulation of the cortex, we used a transparent substrate microelectrode array to map cortical potentials resulting from optogenetic stimulation. Spatial optogenetic stimulation is a new tool for studying neurovascular and neurometabolic coupling. PMID:25388678

Single cell array impedance analysis in a microfluidic device

NASA Astrophysics Data System (ADS)

Altinagac, Emre; Taskin, Selen; Kizil, Huseyin

2016-10-01

Impedance analysis of single cells is presented in this paper. Following the separation of a target cell type by dielectrophoresis in our previous work, this paper focuses on capturing the cells as a single array and performing impedance analysis to point out the signature difference between each cell type. Lab-on-a-chip devices having a titanium interdigitated electrode layer on a glass substrate and a PDMS microchannel are fabricated to capture each cell in a single form and perform impedance analysis. HCT116 (homosapiens colon colorectal carcin) and HEK293 (human embryonic kidney) cells are used in our experiments.

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....

Direct current injection and thermocapillary flow for purification of aligned arrays of single-walled carbon nanotubes

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

Xie, Xu; Islam, Ahmad E.; Seabron, Eric

2015-04-07

Aligned arrays of semiconducting single-walled carbon nanotubes (s-SWNTs) represent ideal configurations for use of this class of material in high performance electronics. Development of means for removing the metallic SWNTs (m-SWNTs) in as-grown arrays represents an essential challenge. Here, we introduce a simple scheme that achieves this type of purification using direct, selective current injection through interdigitated electrodes into the m-SWNTs, to allow their complete removal using processes of thermocapillarity and dry etching. Experiments and numerical simulations establish the fundamental aspects that lead to selectivity in this process, thereby setting design rules for optimization. Single-step purification of arrays that includemore » thousands of SWNTs demonstrates the effectiveness and simplicity of the procedures. The result is a practical route to large-area aligned arrays of purely s-SWNTs with low-cost experimental setups.« less

Superconducting micro-resonator arrays with ideal frequency spacing

NASA Astrophysics Data System (ADS)

Liu, X.; Guo, W.; Wang, Y.; Dai, M.; Wei, L. F.; Dober, B.; McKenney, C. M.; Hilton, G. C.; Hubmayr, J.; Austermann, J. E.; Ullom, J. N.; Gao, J.; Vissers, M. R.

2017-12-01

We present a wafer trimming technique for producing superconducting micro-resonator arrays with highly uniform frequency spacing. With the light-emitting diode mapper technique demonstrated previously, we first map the measured resonance frequencies to the physical resonators. Then, we fine-tune each resonator's frequency by lithographically trimming a small length, calculated from the deviation of the measured frequency from its design value, from the interdigitated capacitor. We demonstrate this technique on a 127-resonator array made from titanium-nitride and show that the uniformity of frequency spacing is greatly improved. The array yield in terms of frequency collisions improves from 84% to 97%, while the quality factors and noise properties are unaffected. The wafer trimming technique provides an easy-to-implement tool to improve the yield and multiplexing density of large resonator arrays, which is important for various applications in photon detection and quantum computing.

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.

1.55 Micrometer Sub-Micron Finger, Interdigitated MSM Photodetector Arrays with Low Dark Current

DTIC Science & Technology

2010-02-02

pf a- IGZO TFTs. IV. RF Characteristics of Room Temperature Deposited Indium Zinc Oxide Thin - Film Transistors Depletion-mode indium zinc...III. High Performance Indium Gallium Zinc Oxide Thin Film Transistors Fabricated On Polyethylene Terephthalate Substrates High-performance...amorphous (a-) InGaZnO-based thin film transistors (TFTs) were fabricated on flexible polyethylene terephthalate (PET) substrates coated with indium

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.

An Electronic-Nose Sensor Node Based on a Polymer-Coated Surface Acoustic Wave Array for Wireless Sensor Network Applications

PubMed Central

Tang, Kea-Tiong; Li, Cheng-Han; Chiu, Shih-Wen

2011-01-01

This study developed an electronic-nose sensor node based on a polymer-coated surface acoustic wave (SAW) sensor array. The sensor node comprised an SAW sensor array, a frequency readout circuit, and an Octopus II wireless module. The sensor array was fabricated on a large K2 128° YX LiNbO3 sensing substrate. On the surface of this substrate, an interdigital transducer (IDT) was produced with a Cr/Au film as its metallic structure. A mixed-mode frequency readout application specific integrated circuit (ASIC) was fabricated using a TSMC 0.18 μm process. The ASIC output was connected to a wireless module to transmit sensor data to a base station for data storage and analysis. This sensor node is applicable for wireless sensor network (WSN) applications. PMID:22163865

An electronic-nose sensor node based on a polymer-coated surface acoustic wave array for wireless sensor network applications.

PubMed

Tang, Kea-Tiong; Li, Cheng-Han; Chiu, Shih-Wen

2011-01-01

This study developed an electronic-nose sensor node based on a polymer-coated surface acoustic wave (SAW) sensor array. The sensor node comprised an SAW sensor array, a frequency readout circuit, and an Octopus II wireless module. The sensor array was fabricated on a large K(2) 128° YX LiNbO3 sensing substrate. On the surface of this substrate, an interdigital transducer (IDT) was produced with a Cr/Au film as its metallic structure. A mixed-mode frequency readout application specific integrated circuit (ASIC) was fabricated using a TSMC 0.18 μm process. The ASIC output was connected to a wireless module to transmit sensor data to a base station for data storage and analysis. This sensor node is applicable for wireless sensor network (WSN) applications.

Nanostructured cavity devices for extracellular stimulation of HL-1 cells.

PubMed

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

2015-01-01

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

Functional connectivity and dynamics of cortical-thalamic networks co-cultured in a dual compartment device

NASA Astrophysics Data System (ADS)

Kanagasabapathi, Thirukumaran T.; Massobrio, Paolo; Barone, Rocco Andrea; Tedesco, Mariateresa; Martinoia, Sergio; Wadman, Wytse J.; Decré, Michel M. J.

2012-06-01

Co-cultures containing dissociated cortical and thalamic cells may provide a unique model for understanding the pathophysiology in the respective neuronal sub-circuitry. In addition, developing an in vitro dissociated co-culture model offers the possibility of studying the system without influence from other neuronal sub-populations. Here we demonstrate a dual compartment system coupled to microelectrode arrays (MEAs) for co-culturing and recording spontaneous activities from neuronal sub-populations. Propagation of electrical activities between cortical and thalamic regions and their interdependence in connectivity is verified by means of a cross-correlation algorithm. We found that burst events originate in the cortical region and drive the entire cortical-thalamic network bursting behavior while mutually weak thalamic connections play a relevant role in sustaining longer burst events in cortical cells. To support these experimental findings, a neuronal network model was developed and used to investigate the interplay between network dynamics and connectivity in the cortical-thalamic system.

Validation of long-term primary neuronal cultures and network activity through the integration of reversibly bonded microbioreactors and MEA substrates.

PubMed

Biffi, Emilia; Menegon, Andrea; Piraino, Francesco; Pedrocchi, Alessandra; Fiore, Gianfranco B; Rasponi, Marco

2012-01-01

In vitro recording of neuronal electrical activity is a widely used technique to understand brain functions and to study the effect of drugs on the central nervous system. The integration of microfluidic devices with microelectrode arrays (MEAs) enables the recording of networks activity in a controlled microenvironment. In this work, an integrated microfluidic system for neuronal cultures was developed, reversibly coupling a PDMS microfluidic device with a commercial flat MEA through magnetic forces. Neurons from mouse embryos were cultured in a 100 µm channel and their activity was followed up to 18 days in vitro. The maturation of the networks and their morphological and functional characteristics were comparable with those of networks cultured in macro-environments and described in literature. In this work, we successfully demonstrated the ability of long-term culturing of primary neuronal cells in a reversible bonded microfluidic device (based on magnetism) that will be fundamental for neuropharmacological studies. Copyright © 2011 Wiley Periodicals, Inc.

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

PubMed

Piilgaard, Henning; Lauritzen, Martin

2009-09-01

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

An AC electroosmotic micropump for circular chromatographic applications.

PubMed

Debesset, S; Hayden, C J; Dalton, C; Eijkel, J C T; Manz, A

2004-08-01

Flow rates of up to 50 microm s(-1) have been successfully achieved in a closed-loop channel using an AC electroosmotic pump. The AC electroosmotic pump is made of an interdigitated array of unequal width electrodes located at the bottom of a channel, with an AC voltage applied between the small and the large electrodes. The flow rate was found to increase linearly with the applied voltage and to decrease linearly with the applied frequency. The pump is expected to be suitable for circular chromatography for the following reasons: the driving forces are distributed over the channel length and the pumping direction is set by the direction of the interdigitated electrodes. Pumping in a closed-loop channel can be achieved by arranging the electrode pattern in a circle. In addition the inherent working principle of AC electroosmotic pumping enables the independent optimisation of the channel height or the flow velocity.

Surface morphology of titanium dioxide (TiO{sub 2}) nanoparticles on aluminum interdigitated device electrodes (IDEs)

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

Azizah, N., E-mail: norazizahparmin84@gmail.com; Gopinath, Subash C. B.; Nadzirah, Sh.

2016-07-06

Titanium dioxide (TiO{sub 2}) nanoparticles based Interdigitated Device Electrodes (IDEs) Nanobiosensor device was developed for intracellular biochemical detection. Fabrication and characterization of Scanning Electron Microscopy (SEM) using IDE nanocoated with TiO{sub 2} was studied in this paper. SEM analysis was carried out at 10 kV acceleration volatege and a 9.8 mA emission current to compare IDE with and without TiO{sub 2} on the surface area. The simple fabrication process, high sensitivity, and fast response of the TiO{sub 2} based IDEs facilitate their applications in a wide range of areas. The small size of semiconductor TiO{sub 2} based IDE for sensitive,more » label-free, real time detection of a wide range of biological species could be explored in vivo diagnostics and array-based screening.« less

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.

Elaboration of ammonia gas sensors based on electrodeposited polypyrrole--cobalt phthalocyanine hybrid films.

PubMed

Patois, Tilia; Sanchez, Jean-Baptiste; Berger, Franck; Fievet, Patrick; Segut, Olivier; Moutarlier, Virginie; Bouvet, Marcel; Lakard, Boris

2013-12-15

The electrochemical incorporation of a sulfonated cobalt phthalocyanine (sCoPc) in conducting polypyrrole (PPy) was done, in the presence or absence of LiClO4, in order to use the resulting hybrid material for the sensing of ammonia. After electrochemical deposition, the morphological features and structural properties of polypyrrole/phthalocyanine hybrid films were investigated and compared to those of polypyrrole films. A gas sensor consisting in platinum microelectrodes arrays was fabricated using silicon microtechnologies, and the polypyrrole and polypyrrole/phthalocyanine films were electrochemically deposited on the platinum microelectrodes arrays of this gas sensor. When exposed to ammonia, polymer-based gas sensors exhibited a decrease in conductance due to the electron exchange between ammonia and sensitive polymer-based layer. The characteristics of the gas sensors (response time, response amplitude, reversibility) were studied for ammonia concentrations varying from 1 ppm to 100 ppm. Polypyrrole/phthalocyanine films exhibited a high sensitivity and low detection limit to ammonia as well as a fast and reproducible response at room temperature. The response to ammonia exposition of polypyrrole films was found to be strongly enhanced thanks to the incorporation of the phthalocyanine in the polypyrrole matrix. © 2013 Elsevier B.V. All rights reserved.

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.

Development of acousto-optic spatial light modulator unit for effective control of light beam intensity and diffraction angle in 3D holographic display applications

NASA Astrophysics Data System (ADS)

Kondalkar, Vijay V.; Ryu, Geonhee; Lee, Yongbeom; Lee, Keekeun

2018-07-01

An acousto-optic (AO) based holographic display unit was developed using surface acoustic wave (SAW) with different wavelength to modulate the diffraction angles, intensities, and phases of light. The new configurations were employed to control two beams simultaneously by using a single chirp inter-digital transducer (IDT), and a micro-lens array was integrated at the end of the waveguide layer to focus the diffracted light on to the screen. Two incident light beams were simultaneously modulated by using different refractive grating periods generated from chirp IDT. A diffraction angle of about 5° was obtained by using a SAW with a frequency of 430 MHz. The increase in the SAW input power enhances the diffraction efficiency of the light beam at the exit. The obtained maximum diffraction efficiency is ~70% at a frequency of 430 MHz. The sloped shape of the waveguide entrance and a tall rounded Ni poles help in coupling the incident light to the waveguide layer. The diffracted beam was collected through the lens, which increased the intensity of light in the viewing plane. COMSOL multi-physics and coupling of mode (COM) modeling were performed to predict the device performance and compared with the experimental results.

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.

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.

Innovative method to suppress local geometry distortions for fabrication of interdigitated electrode arrays with nano gaps

NASA Astrophysics Data System (ADS)

Partel, S.; Urban, G.

2016-03-01

In this paper we present a method to optimize the lithography process for the fabrication of interdigitated electrode arrays (IDA) for a lift-off free electrochemical biosensor. The biosensor is based on amperometric method to allow a signal amplification by redox cycling. We already demonstrated a method to fabricate IDAs with nano gaps with conventional mask aligner lithography and two subsequent deposition processes. By decreasing the distance down to the nanometer range the linewidth variation is becoming the most critical factor and can result in a short circuit of the electrodes. Therefore, the light propagation and the resist pattern of the mask aligner lithography process are simulated to optimize the lithography process. To optimize the outer finger structure assistant features (AsFe) were introduced. The AsFe allow an optimization of the intensity distribution at the electrode fingers. Hence, the periodicity is expanded and the outer structure of the IDA is practically a part of the periodic array. The better CD uniformity can be obtained by adding three assistant features which generate an equal intensity distributions for the complete finger pattern. Considering a mask optimization of the outer structures would also be feasible. However, due to the strong impact of the gap between mask and wafer at contact lithography it is not practicable. The better choice is to create the same intensity distribution for all finger structures. With the introduction of the assistant features large areas with electrode gap sizes in the sub 100 nm region are demonstrated.

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.

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

PubMed

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

2015-04-15

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

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

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.

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

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

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.

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.

Portable Lock-in Amplifier-Based Electrochemical Method to Measure an Array of 64 Sensors for Point-of-Care Applications.

PubMed

Hrdý, Radim; Kynclová, Hana; Klepáčová, Ivana; Bartošík, Martin; Neužil, Pavel

2017-09-05

We present a portable lock-in amplifier-based electrochemical sensing system. The basic unit (cluster) consists of four electrochemical cells (EC), each containing one pseudoreference electrode (PRE) and one working electrode (WE). All four ECs are simultaneously interrogated, each at different frequencies, with square wave pulses superposed on a sawtooth signal for cyclic voltammetry (CV). Lock-in amplification provides independent read-out of four signals, with excellent noise suppression. We expanded a single cluster system into an array of 16 clusters by using electronic switches. The chip with an array of ECs was fabricated using planar technology with a gap between a WE and a PRE of ≈2 μm, which results in partial microelectrode-type behavior. The basic electrode characterization was performed with the model case using a ferricyanide-ferrocyanide redox couple (Fe 2+ /Fe 3+ ) reaction, performing CV and differential pulse voltammetry (DPV). We then used this system to perform cyclic lock-in voltammetry (CLV) to measure concurrently responses of the four ECs. We repeated this method with all 64 ECs on the chip. The standard deviation of a peak oxidation and reduction current in a single channel consisting of 13 ECs was ≈7.46% and ≈5.6%, respectively. The four-EC configuration in each measured spot allows determination of nonperforming ECs and, thus, to eliminate potential false results. This system is built in a portable palm-size format suitable for point-of-care applications. It can perform either individual or multiple measurements of active compounds, such as biomarkers.

Preparation, Applications, and Digital Simulation of Carbon Interdigitated Array Electrodes

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

Liu, Fei; Kolesov, Grigory; Parkinson, Bruce A.

2014-12-16

Carbon interdigitated array (IDA) electrodes with features sizes down to 1.2 μm were fabricated by controlled pyrolysis of patterned photoresist. Cyclic voltam-metry of reversible redox species produced the expected steady-state currents. The collection efficiency depends on the IDA electrode spacing, which ranged from around 2.7 to 16.5 μm, with the smaller dimensions achieving higher collection efficiencies of up to 98%. The signal amplification because of redox cycling makes it possible to detect species at relatively low concentrations (10–5 molar) and the small spacing allows detection of transient electrogenerated species with much shorter lifetimes (submillisecond). Digital simulation software that accounts formore » both the width and height of electrode elements as well as the electrode spacing was developed to model the IDA electrode response. The simulations are in quantitative agreement with experimental data for both a simple fast one electron redox reaction and an electron transfer with a following chemical reaction at the IDAs with larger gaps whereas currents measured for the smallest IDA electrodes, that were larger than the simulated currents, are attributed to convection from induced charge electrokinetic flow. This work was supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the Department of Energy, Office of Science Office of Basic Energy Sciences.« less

Electrical detection of DNA hybridization: three extraction techniques based on interdigitated Al/Al2O3 capacitors.

PubMed

Moreno-Hagelsieb, L; Foultier, B; Laurent, G; Pampin, R; Remacle, J; Raskin, J-P; Flandre, D

2007-04-15

Based on interdigitated aluminum electrodes covered with Al(2)O(3) and silver precipitation via biotin-antibody coupled gold nano-labels as signal enhancement, three complementary electrical methods were used and compared to detect the hybridization of target DNA for concentrations down to the 50 pM of a PCR product from cytochrome P450 2b2 gene. Human hepatic cytochrome P450 (CYP) enzymes participate in detoxification metabolism of xenobiotics. Therefore, determination of mutational status of P450 gene in a patient could have a significant impact on the choice of a medical treatment. Our three electrical extraction procedures are performed on the same interdigitated capacitive sensor lying on a passivated silicon substrate and consist in the measurement of respectively the low-frequency inter-electrodes capacitance, the high-frequency self-resonance frequency, and the equivalent MOS capacitance between the short-circuited electrodes and the backside metallization of the silicon substrate. This study is the first of its kind as it opens the way for correlation studies and noise reduction techniques based on multiple electrical measurements of the same DNA hybridization event with a single sensor.

Enhanced output-performance of piezoelectric poly(vinylidene fluoride trifluoroethylene) fibers-based nanogenerator with interdigital electrodes and well-ordered cylindrical cavities

NASA Astrophysics Data System (ADS)

Gui, Jinzheng; Zhu, Yezi; Zhang, Lingling; Shu, Xi; Liu, Wei; Guo, Shishang; Zhao, Xingzhong

2018-02-01

A piezoelectric nanogenerator based on poly(vinylidene fluoride trifluoroethylene) [P(VDF-TrFE)] nanofibers with an Au interdigital electrode (IDT)/P(VDF-TrFE) nanofiber film/well-ordered cylindrical cavity structure was prepared by combining Au IDTs with a rotary collector to obtain highly aligned P(VDF-TrFE) nanofiber arrays. The Au IDTs work not only as parallel electrodes to collect P(VDF-TrFE) nanofibers during electrospinning but also as charge-collecting electrodes in the nanogenerator. The well-ordered cylindrical cavities improve output performance by enhancing the deformation of P(VDF-TrFE) nanofiber films when subjected to external force. The nanogenerator performs well; as an example of application, we demonstrate energy harvesting from human walking, with a peak output voltage of 5 V and a peak short-circuit current of 1.2 μA. Such a device could have practical applications in wearable, self-powered devices.

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

NASA Astrophysics Data System (ADS)

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

2017-02-01

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

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

NASA Astrophysics Data System (ADS)

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

2007-03-01

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

Generation of electrochemiluminescence at bipolar electrodes: concepts and applications.

PubMed

Bouffier, Laurent; Arbault, Stéphane; Kuhn, Alexander; Sojic, Neso

2016-10-01

Bipolar electrochemistry (BPE) is an unconventional technique where a conducting object is addressed electrochemically in an electrolyte without any wire connection with an external power supply. BPE has been known for decades but remained limited to only a couple of niche applications. However, it is now undergoing a true renewal of interest especially in the context of analytical chemistry. The bipolar electrode exhibits two distinct poles of opposite polarization with respect to the solution. This allows one to separate the localization of sensing elements versus reporting ones. Also, arrays of bipolar microelectrodes can be addressed simultaneously to perform parallel analyses. Among several reporting strategies, the combination of BPE with electro-chemiluminescence (ECL) is the most frequent choice owing to the very simple visual readout provided by ECL. This article reviews the field from the initial reports to the most recent ones, revealing numerous opportunities including novel analytical strategies for the detection of small molecular analytes and biorelevant molecules such as DNA, RNA, peptides, or other biomarkers. Graphical Abstract Principle of electrochemiluminescence generation at one extremity of a bipolar electrode.

Modeling conduction in host-graft interactions between stem cell grafts and cardiomyocytes.

PubMed

Chen, Michael Q; Yu, Jin; Whittington, R Hollis; Wu, Joseph C; Kovacs, Gregory T A; Giovangrandi, Laurent

2009-01-01

Cell therapy has recently made great strides towards aiding heart failure. However, while transplanted cells may electromechanically integrate into host tissue, there may not be a uniform propagation of a depolarization wave between the heterogeneous tissue boundaries. A model using microelectrode array technology that maps the electrical interactions between host and graft tissues in co-culture is presented and sheds light on the effects of having a mismatch of conduction properties at the boundary. Skeletal myoblasts co-cultured with cardiomyocytes demonstrated that conduction velocity significantly decreases at the boundary despite electromechanical coupling. In an attempt to improve the uniformity of conduction with host cells, differentiating human embryonic stem cells (hESC) were used in co-culture. Over the course of four to seven days, synchronous electrical activity was observed at the hESC boundary, implying differentiation and integration. Activity did not extend far past the boundary, and conduction velocity was significantly greater than that of the host tissue, implying the need for other external measures to properly match the conduction properties between host and graft tissue.

Measuring the level of agreement in hematologic and biochemical values between blood sampling sites in leatherback sea turtles (Dermochelys coriacea).

PubMed

Stewart, Kimberly; Mitchell, Mark A; Norton, Terry; Krecek, Rosina C

2012-12-01

Conservation programs to protect endangered sea turtles are being instituted worldwide. A common practice in these programs is to collect blood to evaluate the health of the turtles. Several different venipuncture sites are used to collect blood from sea turtles for hematologic and biochemistry tests, depending on the species. To date, it is unknown what affect venipuncture site may have on sample results. The purpose of this study was to measure the level of agreement between hematologic and biochemistry values collected from the dorsal cervical sinus and the interdigital vein of leatherback (Dermochelys coriacea) sea turtles. Paired heparinized blood samples were obtained from the dorsal cervical sinus and the interdigital vein of 12 adult female nesting leatherback sea turtles on Keys Beach, St. Kitts, West Indies. Even though the sample population was small, the data for each chemistry were normally distributed, except for creatine kinase (CK). There was no significant difference when comparing biochemistry or hematologic values by venipuncture site, except for CK (P = 0.02). The level of agreement between sampling sites was considered good for albumin, calcium, globulin, glucose, packed cell volume, phosphorus, potassium, sodium, total protein, total solids, uric acid, white blood cell count, and all of the individual white cell types, while the level of agreement for aspartate aminotransferase and CK were considered poor. This information, coupled with the fact that the interdigital vein affords a less-invasive procedure, demonstrates that the interdigital vein is an appropriate location to use when establishing a hematologic and biochemical profile for leatherback sea turtles.

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.

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.

A simple and transparent well-aligned ZnO nanowire array ultraviolet photodetector with high responsivity

NASA Astrophysics Data System (ADS)

Yin, Lei; Ding, Hesheng; Yuan, Zhaolin; Huang, Wendeng; Shuai, Chunjiang; Xiong, Zhaoxin; Deng, Jianping; Lv, Tengbo

2018-06-01

Well-aligned zinc oxide (ZnO) nanowire arrays were grown on an interdigital patterned fluorine tin oxide (FTO)-coated glass substrate by a facile chemical bath deposition at low temperature. Morphology, crystalline structure, and optical properties of the ZnO nanowire arrays were analyzed in detail. The results revealed that the ZnO nanowires had wurtzite structure, typically ∼40-60 nm in diameter, and ∼700-800 nm in length, a great number of highly uniform and dense nanowires grew vertically on the substrate to form the well-aligned ZnO nanowire arrays, which had very high optical transmission (>86%) in the visible light region. In addition, the performance of ZnO nanowire arrays ultraviolet (UV) photodetector was systematically examined. The photosensitivity (S), responsivity (R), response and decay time of the photodetector were 703 at +0.2 V, 113 A/W at +5 V, 23 s and 73 s respectively. Also, the photoresponse mechanism of the UV photodetector was illuminated in terms of the oxygen adsorption-photodesorption process.

Dynamic response of a lenticular microlens array using a polyvinyl chloride gel

NASA Astrophysics Data System (ADS)

Li, Xiaolong; Zhou, Zuowei; Ren, Hongwen

2017-12-01

We prepared a lenticular microlens array (LMA) using a polyvinyl chloride (PVC) gel and an interdigitated electrode. By applying a DC voltage to the electrode, the surface of the PVC gel can be waved with an LMA character. When the voltage is removed, the wavy PVC gel can recover its flat surface gradually. With the aid of a polarity-inverted voltage, the recovering time can be largely reduced. The LMA can present a stable dynamic response when it is repetitively impacted by a pulse voltage. The experimental results are given, and the mechanism of reducing the dynamic response time is explained. Our LMA with improved response time has potential applications in sensing, beam steering, biometrics, and displays.

SU-E-T-306: Dosimetric Comparison of Leaf with Or Without Interdigitation in Multiple Brain Metastasis VMAT Treatment Planning

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

NONE

Purpose: To evaluate the effects of leaf with or without interdigitation in multiple brain metastasis volumetric modulated arc therapy (VMAT) plans. Methods: Twenty patients with 2 to 6 brain metastases of our hospital were retrospectively studied to be planned with dual arc VMAT using Monaco 3.3 TPS on the Elekta Synergy linear accelerator. The prescription dose of PTV was 60Gy/30 fractions. Two plans with or without leaf interdigitation were designed. The homogeneity index (HI), conformity index (CI), dose volume histograms (DVHs), monitor unit (MU), treatment time (T), the segments, the dose coverage of the target, were all evaluated. Results: Themore » plans with leaf interdigitation could achieve better CI (p<0.05) than without leaf interdigitation, while no significant difference were found in HI (p> 0.05) and the dose coverage of the target (p> 0.05).The MU,T, and the segments of the plan with leaf interdigitation were more than the plan without leaf interdigitation (p<0.05). There was no significant difference found in radiation dose of spinal cord, lenses and parotids, while the maximum dose of brain stem of leaf without interdigitation was higher than leaf with interdigitation (p< 0.05). It was worth noting that the areas of low dose regions with leaf interdigitation plan were much less than the without leaf interdigitation plan in the doublication planes (p< 0.05). Conclusion: This study shows that leaf with interdigitation has some advantages than leaf without interdigitation in multiple brain metastasis VMAT plans although the clinical relevance remains to be proven.« less

Novel platinum black electroplating technique improving mechanical stability.

PubMed

Kim, Raeyoung; Nam, Yoonkey

2013-01-01

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

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.

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.

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.

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.

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

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

PubMed

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

2017-06-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-06-01

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

Chemicapacitive microsensors for detection of explosives and TICs

NASA Astrophysics Data System (ADS)

Patel, Sanjay V.; Hobson, Stephen T.; Cemalovic, Sabina; Mlsna, Todd E.

2005-10-01

Seacoast Science develops chemical sensors that use polymer-coated micromachined capacitors to measure the dielectric permittivity of an array of selectively absorbing materials. We present recent results demonstrating the sensor technology's capability to detect components in explosives and toxic industrial chemicals. These target chemicals are detected with functionalized polymers or network materials, chosen for their ability to adsorb chemicals. When exposed to vapors or gases, the permittivity of these sorbent materials changes depending on the strength of the vapor-sorbent interaction. Sensor arrays made of ten microcapacitors on a single chip have been previously shown to detect vapors of organic compounds (chemical warfare agents, industrial solvents, fuels) and inorganic gases (SO2, CO2, NO2). Two silicon microcapacitor structures were used, one with parallel electrode plates and the other with interdigitated "finger-like" electrodes. The parallel-plates were approximately 300 μm wide and separated by 750 nm. The interdigitated electrodes were approximately 400 μm long and were elevated above the substrate to provide faster vapor access. Eight to sixteen of these capacitors are fabricated on chips that are 5 x 2 mm and are packaged in less than 50 cm3 with supporting electronics and batteries, all weighing less than 500 grams. The capacitors can be individually coated with different materials creating a small electronic nose that produces different selectivity patterns in response to different chemicals. The resulting system's compact size, low-power consumption and low manufacturing costs make the technology ideal for integration into various systems for numerous 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.

RF-MEMS tunable interdigitated capacitor and fixed spiral inductor for band pass filter applications

NASA Astrophysics Data System (ADS)

Bade, Ladon Ahmed; Dennis, John Ojur; Khir, M. Haris Md; Wen, Wong Peng

2016-11-01

This research presents the tunable Radio Frequency Micro Electromechanical Systems (RF-MEMS) coupled band-pass filter (BPF), which possess a wide tuning range and constructed by using the Chebyshev fourth degree equivalent circuit consisting of fixed inductors and interdigitated tunable capacitors. The suggested method was authenticated by designing a new tunable BPF with a 100% tuning range from 3.1 GHz to 4.9 GHz. The Metal Multi-User MEMS Process (Metal MUMPs) was involved in the process of design of this band-pass filter. It aimed to achieve the reconfiguration of frequencies and show high efficiency of RF in the applications that using Ultra Wide Band (UWB) such as wireless sensor networks. The RF performance of this filter was found to be very satisfactory due to its simple fabrication. Moreover, it showed less insertion loss of around 4 dB and high return loss of around 20 dB.

Radio frequency focused interdigital linear accelerator

DOEpatents

Swenson, Donald A.; Starling, W. Joel

2006-08-29

An interdigital (Wideroe) linear accelerator employing drift tubes, and associated support stems that couple to both the longitudinal and support stem electromagnetic fields of the linac, creating rf quadrupole fields along the axis of the linac to provide transverse focusing for the particle beam. Each drift tube comprises two separate electrodes operating at different electrical potentials as determined by cavity rf fields. Each electrode supports two fingers, pointing towards the opposite end of the drift tube, forming a four-finger geometry that produces an rf quadrupole field distribution along its axis. The fundamental periodicity of the structure is equal to one half of the particle wavelength .beta..lamda., where .beta. is the particle velocity in units of the velocity of light and .lamda. is the free space wavelength of the rf. Particles are accelerated in the gaps between drift tubes. The particle beam is focused in regions inside the drift tubes.

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

Duan, J

Purpose: The aim of this work is to study the dosimetric impact of leaf interdigitation in prostate cancer dynamic IMRT treatment planning. Methods: Fifteen previously treated prostate cancer patients were replanned for dynamic IMRT (dMLC) with and without leaf interdigitation using Monaco 3.3 TPS on the Elekta Synergy linear accelerator. The prescription dose of PTV was 70Gy/35 fractions. Various dosimetric variables, such as PTV coverage, OAR sparing, delivery efficiency and optimization time, were evaluated for each plan. Results: Interdigitation did not improve the coverage, HI and CI for PTV. Regarding OARs, sparing was equivalent with and without interdigitation. Interdigitation shownmore » an increase in MUs and segments. It was worth noting that leaf interdigitation saved the optimization time. Conclusion: This study shows that leaf interdigitation does not improve plan quality when performing dMLC treatment plan for prostate cancer. However, it influences delivery efficiency and optimization time. Interdigitation may gain efficiency for dosimetrist when designing the prostate cancer dMLC plans.« less

Silica Nanowires: Growth, Integration, and Sensing Applications

PubMed Central

Kaushik, Ajeet; Kumar, Rajesh; Huey, Eric; Bhansali, Shekhar; Nair, Narayana; Nanir, Madhavan

2014-01-01

This review (with 129 refs.) gives an overview on how the integration of silica nanowires (NWs) into micro-scale devices has resulted, in recent years, in simple yet robust nano-instrumentation with improved performance in targeted application areas such as sensing. This has been achieved by the use of appropriate techniques such as di-electrophoresis and direct vapor-liquid-growth phenomena, to restrict the growth of NWs to site-specific locations. This also has eliminated the need for post-growth processing and enables nanostructures to be placed on pre-patterned substrates. Various kinds of NWs have been investigated to determine how their physical and chemical properties can be tuned for integration into sensing structures. NWs integrated onto interdigitated micro-electrodes have been applied to the determination of gases and biomarkers. The technique of directly growing NWs eliminates the need for their physical transfer and thus preserves their structure and performance, and further reduces the costs of fabrication. The biocompatibility of NWs also has been studied with respect to possible biological applications. This review addresses the challenges in growth and integration of NWs to understand related mechanism on biological contact or gas exposure and sensing performance for personalized health and environmental monitoring. PMID:25382871

Stable Rotation of Microparticles using a Combination of Dielectrophoresis and Electroosmosis

NASA Astrophysics Data System (ADS)

Dutta, Prashanta; Rezanoor, Walid

2016-11-01

Electric field induced microparticle rotation has become a powerful technique to evaluate cell membrane dielectric properties and cell morphology. In this study, stable rotations of microparticles are demonstrated in a stationary AC electric field created from a set of coplanar interdigitated microelectrodes. The medium, particle size, and material are carefully chosen so that particle can be controlled by dielectrophoretic force, while a sufficiently high AC electroosmotic flow is produced for continuous particle rotation. Stable rotation up to 218 rpm is observed at 30 Vp-p applied sinusoidal potential in the frequency range of 80 - 1000 Hz. The particle spin rate observed from the experimental study is then validated with a numerical model. The model is formulated around complex charge conservation equation to determine the electric potential distribution in the domain. Stokes equation is employed to solve for AC electroosmotic fluid flow in the domain. Complexity arising from nonlinear potential drop across the electric double layer due to the application of a very large electric potential is also addressed by introducing modified capacitance equation which considers steric effect. This work was supported in part by the U.S. National Science Foundation under Grant No. DMS 1317671.

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

Fabrication of Out-of-Plane Electrodes for ACEO Pumps

NASA Astrophysics Data System (ADS)

Senousy, Yehya; Harnett, Cindy

2012-02-01

This abstract reports the fabrication process of a novel AC Electrosmosis (ACEO) pump with out of plane asymmetric interdigitated electrodes. A self-folding technique is used to fabricate the electrodes, that depends on the strain mismatch between the tensile stressed film (metal layer) and the compressive stress film (oxidized silicon layer). The electrodes roll up with a well-defined radius of curvature in the range of 100-200 microns. Two different electrical signals are connected to alternating electrodes using an insulating silicon nitride barrier that allows circuits to cross over each other without shorting. Electroosmotic micropumps are essential for low-cost, power-efficient microfluidic lab-on-chip devices used in diverse application such as analytical probes, drug delivery systems and surgical tools. ACEO pumps have been developed to address the drawbacks of the DCEO pumps such as the faradic reaction and gas bubbles. The original ACEO microfluidic pump was created with planar arrays of asymmetric interdigitated electrodes at the bottom of the channel. This rolled-up tube design improves on the planar design by including the channel walls and ceiling in the active pumping surface area of the device.

Realization of deep 3D metal electrodes in diamond radiation detectors

NASA Astrophysics Data System (ADS)

Wulz, Thomas; Gerding, William; Lavrik, Nickolay; Briggs, Dayrl; Srijanto, Bernadeta; Lester, Kevin; Hensley, Dale; Spanier, Stefan; Lukosi, Eric

2018-05-01

A fabrication technique to create 3D diamond detectors is presented. Deep reactive ion etching was used to create an array of through-diamond vias (TDVs) in a 2 × 2 × 0.15 mm3 electronic grade single crystal diamond detector. The diameter of the TDVs was nominally 30 μm with a pitch of 100 μm between them. The TDVs were filled with chromium using hexavalent chromium electroplating to create 3D electrodes, which were connected electrically by interdigitated electrodes. The fabricated 3D diamond detector responded to both alpha particles and X-rays, exhibiting a charge collection efficiency of 52.3% at 200 V. Comparing to a diamond detector with the same interdigitated electrodes, but no 3D electrodes, confirms that the 3D electrodes are electrically active within the device. The average resistivity of the 3D electrodes is 2.89 ± 0.03 × 10-5 Ω cm, near that of bulk chromium. These results indicate that this fabrication technique is a potential option for 3D diamond detector fabrication.

A dc amplifier for nuclear particle measurement

NASA Technical Reports Server (NTRS)

Macnee, A. B.; Masnari, N. A.

1978-01-01

A monolithic preamplifier-postamplifier combination has been developed for use with solid state particle detectors. The direct coupled amplifiers employ interdigitated n-channel JFET's, diodes, and diffused resistors. The circuits developed demonstrate the feasibility of matching the performance of existing discrete component designs. The fabrication procedures for the monolithic amplifier fabrication are presented and the results of measurements on a limited number of sample amplifiers are given.

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.

Detection of radio-frequency modulated optical signals by two and three terminal microwave devices

NASA Technical Reports Server (NTRS)

Bhasin, K. B.; Simons, R. N.; Wojtczuk, S.

1987-01-01

An interdigitated photoconductor (two terminal device) on GaAlAs/GaAs heterostructure was fabricated and tested by an electro-optical sampling technique. Further, the photoresponse of GaAlAs/GaAs HEMT (three terminal device) was obtained by illuminating the device with an optical signal modulated up to 8 GHz. Gain-bandwidth product, response time, and noise properties of photoconductor and HEMT devices were obtained. Monolithic integration of these photodetectors with GaAs microwave devices for optically controlled phased array antenna applications is discussed.

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.

Monitoring and Evaluation of Alcoholic Fermentation Processes Using a Chemocapacitor Sensor Array

PubMed Central

Oikonomou, Petros; Raptis, Ioannis; Sanopoulou, Merope

2014-01-01

The alcoholic fermentation of Savatiano must variety was initiated under laboratory conditions and monitored daily with a gas sensor array without any pre-treatment steps. The sensor array consisted of eight interdigitated chemocapacitors (IDCs) coated with specific polymers. Two batches of fermented must were tested and also subjected daily to standard chemical analysis. The chemical composition of the two fermenting musts differed from day one of laboratory monitoring (due to different storage conditions of the musts) and due to a deliberate increase of the acetic acid content of one of the musts, during the course of the process, in an effort to spoil the fermenting medium. Sensor array responses to the headspace of the fermenting medium were compared with those obtained either for pure or contaminated samples with controlled concentrations of standard ethanol solutions of impurities. Results of data processing with Principal Component Analysis (PCA), demonstrate that this sensing system could discriminate between a normal and a potential spoiled grape must fermentation process, so this gas sensing system could be potentially applied during wine production as an auxiliary qualitative control instrument. PMID:25184490

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.

COUPLED MULTI-ELECTRODE INVESTIGATION OF CREVICE CORROSION OF 316 STAINLESS STEEL

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

F. Bocher, J. R. Scully

2006-01-30

Crevice corrosion is currently studied using either one of two techniques depending on the data needed. The first method is a multi-crevice former over a metallic sample; this provides information on the severity of crevice corrosion (depth, position, frequency) but delivers little to no electrochemical information [1]. The second method involves the potentiodynamic or potentiostatic study of an uncreviced sample in model crevice solution or under a crevice former in aggressive solution [2]. Crevice corrosion is highly dependent on the position in the crevice. The distance from the crevice mouth will affect the depth of attack, the solution composition andmore » pH, and the ohmic drop and the true potential in the crevice [3-6]. These in turn affect the current density as a function of potential and position. An Multi-Channel Micro-Electrode Analyzer' (MMA) has been recently used to demonstrate the interaction between localized corrosion sites (pitting corrosion and intergranular corrosion) [7]. MMA can provide spatial resolution of electrochemical properties in the crevice. By coupling such a tool with scaling laws derived from experimental data (a simple equation linking the depth of crevice corrosion initiation to the crevice gap), it is possible to produce highly instrumented crevices, rescaled to enable spatial resolution of local corrosion processes. In this study, the use of multi-wires arrays (up to 100 closed packed wires simulating a planar electrode, divided in 10 distinctively controllable groups) electrically coupled through zero resistance ammeters enables the observation of the current evolution as a function of position inside and outside the crevice. For instance, the location of crevice initiation sites and propagation behavior can be studied under various conditions. Experiments can be conducted with various realistic variables. These can either be electrochemical (such as proximate cathode) or physical (crevice former material or position). Using new impedance-capable MMA, it is also possible to monitor the film breakdown and the early stages of crevice corrosion as a function of the wires position. In this talk, the use of multi-electrode array to study crevice corrosion of 316 stainless steel and a Ni-Cr-Mo alloy is reviewed.« less

COUPLED MULTI-ELECTRODE INVESTIGATION OF CREVICE CORROSION OF 316 STAINLESS STEEL

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

F. Bocher and J. R. Scully

2006-01-30

Crevice corrosion is currently studied using either one of two techniques depending on the data needed. The first method is a multi-crevice former over a metallic sample; this provides information on the severity of crevice corrosion (depth, position, frequency) but delivers little to no electrochemical information [1]. The second method involves the potentiodynamic or potentiostatic study of an uncreviced sample in model crevice solution or under a crevice former in aggressive solution [2]. Crevice corrosion is highly dependent on the position in the crevice. The distance from the crevice mouth will affect the depth of attack, the solution composition andmore » pH, and the ohmic drop and the true potential in the crevice [3-6]. These in turn affect the current density as a function of potential and position. A Multi-Channel Micro-Electrode Analyzer (MMA) has been recently used to demonstrate the interaction between localized corrosion sites (pitting corrosion and intergranular corrosion) [7]. MMA can provide spatial resolution of electrochemical properties in the crevice. By coupling such a tool with scaling laws derived from experimental data (a simple equation linking the depth of crevice corrosion initiation to the crevice gap), it is possible to produce highly instrumented crevices, rescaled to enable spatial resolution of local corrosion processes. In this study, the use of multi-wires arrays (up to 100 closed packed wires simulating a planar electrode, divided in 10 distinctively controllable groups) electrically coupled through zero resistance ammeters enables the observation of the current evolution as a function of position inside and outside the crevice. For instance, the location of crevice initiation sites and propagation behavior can be studied under various conditions. Experiments can be conducted with various realistic variables. These can either be electrochemical (such as proximate cathode) or physical (crevice former material or position). Using new impedance-capable MMA, it is also possible to monitor the film breakdown and the early stages of crevice corrosion as a function of the wires position. In this talk, the use of multi-electrode array to study crevice corrosion of 316 stainless steel and a Ni-Cr-Mo alloy is reviewed.« less

Tunable Nanowire Patterning Using Standing Surface Acoustic Waves

PubMed Central

Chen, Yuchao; Ding, Xiaoyun; Lin, Sz-Chin Steven; Yang, Shikuan; Huang, Po-Hsun; Nama, Nitesh; Zhao, Yanhui; Nawaz, Ahmad Ahsan; Guo, Feng; Wang, Wei; Gu, Yeyi; Mallouk, Thomas E.; Huang, Tony Jun

2014-01-01

Patterning of nanowires in a controllable, tunable manner is important for the fabrication of functional nanodevices. Here we present a simple approach for tunable nanowire patterning using standing surface acoustic waves (SSAW). This technique allows for the construction of large-scale nanowire arrays with well-controlled patterning geometry and spacing within 5 seconds. In this approach, SSAWs were generated by interdigital transducers (IDTs), which induced a periodic alternating current (AC) electric field on the piezoelectric substrate and consequently patterned metallic nanowires in suspension. The patterns could be deposited onto the substrate after the liquid evaporated. By controlling the distribution of the SSAW field, metallic nanowires were assembled into different patterns including parallel and perpendicular arrays. The spacing of the nanowire arrays could be tuned by controlling the frequency of the surface acoustic waves. Additionally, we observed 3D spark-shape nanowire patterns in the SSAW field. The SSAW-based nanowire-patterning technique presented here possesses several advantages over alternative patterning approaches, including high versatility, tunability, and efficiency, making it promising for device applications. PMID:23540330

Aquaporin 0 Modulates Lens Gap Junctions in the Presence of Lens-Specific Beaded Filament Proteins

PubMed Central

Kumari, Sindhu; Gao, Junyuan; Mathias, Richard T.; Sun, Xiurong; Eswaramoorthy, Amizhdini; Browne, Nicholas; Zhang, Nigel

2017-01-01

Purpose The objective of this study was to understand the molecular and physiologic mechanisms behind the lens cataract differences in Aquaporin 0-knockout-Heterozygous (AQP0-Htz) mice developed in C57 and FVB (lacks beaded filaments [BFs]) strains. Methods Lens transparency was studied using dark field light microscopy. Water permeability (Pf) was measured in fiber cell membrane vesicles. Western blotting/immunostaining was performed to verify expression of BF proteins and connexins. Microelectrode-based intact lens intracellular impedance was measured to determine gap junction (GJ) coupling resistance. Lens intracellular hydrostatic pressure (HP) was determined using a microelectrode/manometer system. Results Lens opacity and spherical aberration were more distinct in AQP0-Htz lenses from FVB than C57 strains. In either background, compared to wild type (WT), AQP0-Htz lenses showed decreased Pf (approximately 50%), which was restored by transgenic expression of AQP1 (TgAQP1/AQP0-Htz), but the opacities and differences between FVB and C57 persisted. Western blotting revealed no change in connexin expression levels. However, in C57 AQP0-Htz and TgAQP1/AQP0-Htz lenses, GJ coupling resistance decreased approximately 2.8-fold and the HP gradient decreased approximately 1.9-fold. Increased Pf in TgAQP1/AQP0-Htz did not alter GJ coupling resistance or HP. Conclusions In C57 AQP0-Htz lenses, GJ coupling resistance decreased. HP reduction was smaller than the coupling resistance reduction, a reflection of an increase in fluid circulation, which is one reason for the less severe cataract in C57 than FVB. Overall, our results suggest that AQP0 modulates GJs in the presence of BF proteins to maintain lens transparency and homeostasis. PMID:29196765

Aquaporin 0 Modulates Lens Gap Junctions in the Presence of Lens-Specific Beaded Filament Proteins.

PubMed

Kumari, Sindhu; Gao, Junyuan; Mathias, Richard T; Sun, Xiurong; Eswaramoorthy, Amizhdini; Browne, Nicholas; Zhang, Nigel; Varadaraj, Kulandaiappan

2017-12-01

The objective of this study was to understand the molecular and physiologic mechanisms behind the lens cataract differences in Aquaporin 0-knockout-Heterozygous (AQP0-Htz) mice developed in C57 and FVB (lacks beaded filaments [BFs]) strains. Lens transparency was studied using dark field light microscopy. Water permeability (Pf) was measured in fiber cell membrane vesicles. Western blotting/immunostaining was performed to verify expression of BF proteins and connexins. Microelectrode-based intact lens intracellular impedance was measured to determine gap junction (GJ) coupling resistance. Lens intracellular hydrostatic pressure (HP) was determined using a microelectrode/manometer system. Lens opacity and spherical aberration were more distinct in AQP0-Htz lenses from FVB than C57 strains. In either background, compared to wild type (WT), AQP0-Htz lenses showed decreased Pf (approximately 50%), which was restored by transgenic expression of AQP1 (TgAQP1/AQP0-Htz), but the opacities and differences between FVB and C57 persisted. Western blotting revealed no change in connexin expression levels. However, in C57 AQP0-Htz and TgAQP1/AQP0-Htz lenses, GJ coupling resistance decreased approximately 2.8-fold and the HP gradient decreased approximately 1.9-fold. Increased Pf in TgAQP1/AQP0-Htz did not alter GJ coupling resistance or HP. In C57 AQP0-Htz lenses, GJ coupling resistance decreased. HP reduction was smaller than the coupling resistance reduction, a reflection of an increase in fluid circulation, which is one reason for the less severe cataract in C57 than FVB. Overall, our results suggest that AQP0 modulates GJs in the presence of BF proteins to maintain lens transparency and homeostasis.

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.

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

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.

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

PubMed Central

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

2012-01-01

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

Bioanalytical and chemical sensors using living taste, olfactory, and neural cells and tissues: a short review.

PubMed

Wu, Chunsheng; Lillehoj, Peter B; Wang, Ping

2015-11-07

Biosensors utilizing living tissues and cells have recently gained significant attention as functional devices for chemical sensing and biochemical analysis. These devices integrate biological components (i.e. single cells, cell networks, tissues) with micro-electro-mechanical systems (MEMS)-based sensors and transducers. Various types of cells and tissues derived from natural and bioengineered sources have been used as recognition and sensing elements, which are generally characterized by high sensitivity and specificity. This review summarizes the state of the art in tissue- and cell-based biosensing platforms with an emphasis on those using taste, olfactory, and neural cells and tissues. Many of these devices employ unique integration strategies and sensing schemes based on sensitive transducers including microelectrode arrays (MEAs), field effect transistors (FETs), and light-addressable potentiometric sensors (LAPSs). Several groups have coupled these hybrid biosensors with microfluidics which offers added benefits of small sample volumes and enhanced automation. While this technology is currently limited to lab settings due to the limited stability of living biological components, further research to enhance their robustness will enable these devices to be employed in field and clinical settings.

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, Fei; Divan, Ralu; Parkinson, Bruce A.

2015-06-29

Carbon interdigitated array (IDA) electrodes have been applied to study the homogeneous hydrogen evolution electrocatalyst [Ni(PPh2NBn2)2]2+ (where PPh2NBn2 is 1,5-dibenzyl-3,7-diphenyl-1,5-diaza-3,7-diphosphacyclooctane). The existence of reaction intermediates in the catalytic cycle is inferred from the electrochemical behavior of a glassy carbon disk electrodes and carbon IDA electrodes. The currents on IDA electrodes for an EC’ (electron transfer reaction followed by a catalytic reaction) mechanism are derived from the number of redox cycles and the contribution of non-catalytic currents. The catalytic reaction rate constant was then extracted from the IDA current equations. Applying the IDA current and kinetic equations to the electrochemical responsemore » of the [Ni(PPh2NBn2)2]2+ catalyst yielded a rate constant of 0.10 s-1 for the hydrogen evolution reaction that agrees with the literature value. The quantitative analysis of IDA cyclic voltammetry can be used as a simple and straightforward method for determining rate constants in other catalytic systems. This work was supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the Department of Energy, Office of Science, Office of Basic Energy Sciences. Pacific Northwest National Laboratory is operated by Battelle for DOE. Use of the Center for Nanoscale Materials was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357.« less

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.

Retinoic acid-independent expression of Meis2 during autopod patterning in the developing bat and mouse limb.

PubMed

Mason, Mandy K; Hockman, Dorit; Curry, Lyle; Cunningham, Thomas J; Duester, Gregg; Logan, Malcolm; Jacobs, David S; Illing, Nicola

2015-01-01

The bat has strikingly divergent forelimbs (long digits supporting wing membranes) and hindlimbs (short, typically free digits) due to the distinct requirements of both aerial and terrestrial locomotion. During embryonic development, the morphology of the bat forelimb deviates dramatically from the mouse and chick, offering an alternative paradigm for identifying genes that play an important role in limb patterning. Using transcriptome analysis of developing Natal long-fingered bat (Miniopterus natalensis) fore- and hindlimbs, we demonstrate that the transcription factor Meis2 has a significantly higher expression in bat forelimb autopods compared to hindlimbs. Validation by reverse transcriptase and quantitative polymerase chain reaction (RT-qPCR) and whole mount in situ hybridisation shows that Meis2, conventionally known as a marker of the early proximal limb bud, is upregulated in the bat forelimb autopod from CS16. Meis2 expression is localised to the expanding interdigital webbing and the membranes linking the wing to the hindlimb and tail. In mice, Meis2 is also expressed in the interdigital region prior to tissue regression. This interdigital Meis2 expression is not activated by retinoic acid (RA) signalling as it is present in the retained interdigital tissue of Rdh10 (trex/trex) mice, which lack RA. Additionally, genes encoding RA-synthesising enzymes, Rdh10 and Aldh1a2, and the RA nuclear receptor Rarβ are robustly expressed in bat fore- and hindlimb interdigital tissues indicating that the mechanism that retains interdigital tissue in bats also occurs independently of RA signalling. Mammalian interdigital Meis2 expression, and upregulation in the interdigital webbing of bat wings, suggests an important role for Meis2 in autopod development. Interdigital Meis2 expression is RA-independent, and retention of interdigital webbing in bat wings is not due to the suppression of RA-induced cell death. Rather, RA signalling may play a role in the thinning (rather than complete loss) of the interdigital tissue in the bat forelimb, while Meis2 may interact with other factors during both bat and mouse autopod development to maintain a pool of interdigital cells that contribute to digit patterning and growth.

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.

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.

A Portable Impedance Immunosensing System for Rapid Detection of Salmonella Typhimurium

PubMed Central

Wen, Tao; Wang, Ronghui; Sotero, America; Li, Yanbin

2017-01-01

Salmonella Typhimurium is one of the most dangerous foodborne pathogens and poses a significant threat to human health. The objective of this study was to develop a portable impedance immunosensing system for rapid and sensitive detection of S. Typhimurium in poultry. The developed portable impedance immunosensing system consisted of a gold interdigitated array microelectrode (IDAM), a signal acquisitive interface and a laptop computer with LabVIEW software. The IDAM was first functionalized with 16-Mercaptohexadecanoic acid, and streptavidin was immobilized onto the electrode surface through covalent bonding. Then, biotin-labelled S. Typhimurium-antibody was immobilized onto the IDAM surface. Samples were dropped on the surface of the IDAM and the S. Typhimurium cells in the samples were captured by the antibody on the IDAM. This resulted in impedance changes that were measured and displayed with the LabVIEW software. An equivalent circuit of the immunosensor demonstrated that the largest change in impedance was due to the electron-transfer resistance. The equivalent circuit showed an increase of 35% for the electron-transfer resistance value compared to the negative control. The calibration result indicated that the portable impedance immunosensing system could be used to measure the standard impedance elements, and it had a maximum error of measurement of approximately 13%. For pure culture detection, the system had a linear relationship between the impedance change and the logarithmic value of S. Typhimurium cells ranging from 76 to 7.6 × 106 CFU (colony-forming unit) (50 μL)−1. The immunosensor also had a correlation coefficient of 0.98, and a high specificity for detection of S. Typhimurium cells with a limit of detection (LOD) of 102 CFU (50 μL)−1. The detection time from the moment a sample was introduced to the display of the results was 1 h. To conclude, the portable impedance immunosensing system for detection of S. Typhimurium achieved an LOD that is comparable with commercial electrochemical impedance instruments. The developed impedance immunosensor has advantages in portability, low cost, rapid detection and label-free features showing a great potential for in-field detection of foodborne pathogens. PMID:28846643

A Portable Impedance Immunosensing System for Rapid Detection of Salmonella Typhimurium.

PubMed

Wen, Tao; Wang, Ronghui; Sotero, America; Li, Yanbin

2017-08-28

Salmonella Typhimurium is one of the most dangerous foodborne pathogens and poses a significant threat to human health. The objective of this study was to develop a portable impedance immunosensing system for rapid and sensitive detection of S . Typhimurium in poultry. The developed portable impedance immunosensing system consisted of a gold interdigitated array microelectrode (IDAM), a signal acquisitive interface and a laptop computer with LabVIEW software. The IDAM was first functionalized with 16-Mercaptohexadecanoic acid, and streptavidin was immobilized onto the electrode surface through covalent bonding. Then, biotin-labelled S . Typhimurium -antibody was immobilized onto the IDAM surface. Samples were dropped on the surface of the IDAM and the S . Typhimurium cells in the samples were captured by the antibody on the IDAM. This resulted in impedance changes that were measured and displayed with the LabVIEW software. An equivalent circuit of the immunosensor demonstrated that the largest change in impedance was due to the electron-transfer resistance. The equivalent circuit showed an increase of 35% for the electron-transfer resistance value compared to the negative control. The calibration result indicated that the portable impedance immunosensing system could be used to measure the standard impedance elements, and it had a maximum error of measurement of approximately 13%. For pure culture detection, the system had a linear relationship between the impedance change and the logarithmic value of S . Typhimurium cells ranging from 76 to 7.6 × 10⁶ CFU (colony-forming unit) (50 μL) -1 . The immunosensor also had a correlation coefficient of 0.98, and a high specificity for detection of S . Typhimurium cells with a limit of detection (LOD) of 10² CFU (50 μL) -1 . The detection time from the moment a sample was introduced to the display of the results was 1 h. To conclude, the portable impedance immunosensing system for detection of S . Typhimurium achieved an LOD that is comparable with commercial electrochemical impedance instruments. The developed impedance immunosensor has advantages in portability, low cost, rapid detection and label-free features showing a great potential for in-field detection of foodborne pathogens.

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

Ring modulators with enhanced efficiency based on standing-wave operation on a field-matched, interdigitated p-n junction.

PubMed

Pavanello, Fabio; Zeng, Xiaoge; Wade, Mark T; Popović, Miloš A

2016-11-28

We propose ring modulators based on interdigitated p-n junctions that exploit standing rather than traveling-wave resonant modes to improve modulation efficiency, insertion loss and speed. Matching the longitudinal nodes and antinodes of a standing-wave mode with high (contacts) and low (depletion regions) carrier density regions, respectively, simultaneously lowers loss and increases sensitivity significantly. This approach permits further to relax optical constraints on contacts placement and can lead to lower device capacitance. Such structures are well-matched to fabrication in advanced microelectronics CMOS processes. Device architectures that exploit this concept are presented along with their benefits and drawbacks. A temporal coupled mode theory model is used to investigate the static and dynamic response. We show that modulation efficiencies or loss Q factors up to 2 times higher than in previous traveling-wave geometries can be achieved leading to much larger extinction ratios. Finally, we discuss more complex doping geometries that can improve carrier dynamics for higher modulation speeds in this context.

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

Integrated titanium dioxide (TiO2) nanoparticles on interdigitated device electrodes (IDEs) for pH analysis

NASA Astrophysics Data System (ADS)

Azizah, N.; Hashim, U.; Arshad, M. K. Md.; Gopinath, Subash C. B.; Nadzirah, Sh.; Farehanim, M. A.; Fatin, M. F.; Ruslinda, A. R.; Ayub, R. M.

2016-07-01

Titanium dioxide (TiO2) nanoparticles based Interdigitated Device Electrodes (IDEs) Nanobiosensor device was developed for intracellular biochemical detection. Fabrication and characterization of pH sensors using IDE nanocoated with TiO2 was studied in this paper. In this paper, a preliminary assessment of this intracellular sensor with electrical measurement under different pH levels. 3-aminopropyltriethoxysilane (APTES) was used to enhance the sensitivity of titanium dioxide layer as well as able to provide surface modification by undergoing protonation and deprotonation process. Different types of pH solution provide different resistivity and conductivity towards the surface. Base solution has the higher current compared to an acid solution. Amine and oxide functionalized TiO2 based IDE exhibit pH-dependent could be understood in terms of the change in surface charge during protonation and deprotonation. The simple fabrication process, high sensitivity, and fast response of the TiO2 based IDEs facilitate their applications in a wide range of areas. The small size of semiconductor TiO2 based IDE for sensitive, label-free, real time detection of a wide range of biological species could be explored in vivo diagnostics and array-based screening.

A rapid and sensitive alcohol oxidase/catalase conductometric biosensor for alcohol determination.

PubMed

Hnaien, M; Lagarde, F; Jaffrezic-Renault, N

2010-04-15

A new conductometric biosensor has been developed for the determination of short chain primary aliphatic alcohols. The biosensor assembly was prepared through immobilization of alcohol oxidase from Hansenula sp. and bovine liver catalase in a photoreticulated poly(vinyl alcohol) membrane at the surface of interdigitated microelectrodes. The local conductivity increased rapidly after alcohol addition, reaching steady-state within 10 min. The sensitivity was maximal for methanol (0.394+/-0.004 microS microM(-1), n=5) and decreased by increasing the alcohol chain length. The response was linear up to 75 microM for methanol, 70 microM for ethanol and 65 microM for 1-propanol and limits of detection were 0.5 microM, 1 microM and 3 microM, respectively (S/N=3). No significant loss of the enzyme activities was observed after 3 months of storage at 4 degrees C in a 20mM phosphate buffer solution pH 7.2 (two or three measurements per week). After 4 months, 95% of the initial signal still remained. The biosensor response to ethanol was not significantly affected by acetic, lactic, ascorbic, malic, oxalic, citric, tartaric acids or glucose. The bi-enzymatic sensor was successfully applied to the determination of ethanol in different alcoholic beverages. (c) 2009 Elsevier B.V. All rights reserved.

Interdigitation Zone Band Restoration After Treatment of Diabetic Macular Edema.

PubMed

Serizawa, Satoshi; Ohkoshi, Kishiko; Minowa, Yuko; Soejima, Kumiko

2016-09-01

To investigate whether the integrity of the interdigitation zone band, the ellipsoid zone band, and the external limiting membrane are reliable markers of treatment outcome in diabetic macular edema (DME). In this retrospective study, we examined 41 treatment-naïve eyes (38 patients) with DME that were treated with laser therapy, pharmacotherapy, and/or vitrectomy. Best-corrected visual acuity and the integrity of the interdigitation zone band, the ellipsoid zone band, and the external limiting membrane were assessed before treatment and at 3, 6, and 12 months after DME treatment. One year after treatment, the external limiting membrane, ellipsoid zone band, and interdigitation zone band were completely visible in 30 (73.2%), 24 (58.5%), and 2 (4.9%) eyes, respectively. Interdigitation zone band status improved significantly (P = 0.005) 1 year after treatment. The interdigitation zone did not improve in the absence of the ellipsoid zone band. Likewise, ellipsoid zone status did not improve in the absence of the external limiting membrane at any time after treatment. The results of this study show that restoration of the interdigitation zone band constitutes a very sensitive marker of DME treatment outcome when the ellipsoid zone band is visible before treatment.

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.

Design and Fabrication of Interdigital Nanocapacitors Coated with HfO2

PubMed Central

González, Gabriel; Kolosovas-Machuca, Eleazar Samuel; López-Luna, Edgar; Hernández-Arriaga, Heber; González, Francisco Javier

2015-01-01

In this article nickel interdigital capacitors were fabricated on top of silicon substrates. The capacitance of the interdigital capacitor was optimized by coating the electrodes with a 60 nm layer of HfO2. An analytical solution of the capacitance was compared to electromagnetic simulations using COMSOL and with experimental measurements. Results show that modeling interdigital capacitors using Finite Element Method software such as COMSOL is effective in the design and electrical characterization of these transducers. PMID:25602271

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.

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.

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.

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.

Design of interdigital spiral and concentric capacitive sensors for materials evaluation

NASA Astrophysics Data System (ADS)

Chen, Tianming; Bowler, Nicola

2013-01-01

This paper describes the design of two circular coplanar interdigital sensors with i) a spiral interdigital configuration and ii) a concentric interdigital configuration for the nondestructive evaluation of multilayered dielectric structures. A numerical model accounting for sensor geometry, test-piece geometry and real permittivity, and metal electrode thickness has been developed to calculate the capacitance of the sensors when in contact with a planar test-piece comprising up to four layers. Compared with a disk-and-ring coplanar capacitive sensor developed previously, the interdigital configurations are predicted to have higher signal-to-noise ratio and better accuracy in materials characterization. The disk-and-ring configuration, on the other hand, possesses advantages such as deeper penetration depth and better immunity to lift-off variations.

Quantitative Comparison of Enzyme Immobilization Strategies for Glucose Biosensing in Real-Time Using Fast-Scan Cyclic Voltammetry Coupled with Carbon-Fiber Microelectrodes.

PubMed

Smith, Samantha K; Lugo-Morales, Leyda Z; Tang, C; Gosrani, Saahj P; Lee, Christie A; Roberts, James G; Morton, Stephen W; McCarty, Gregory S; Khan, Saad A; Sombers, Leslie A

2018-05-22

Electrochemical monitoring of non-electroactive species requires a biosensor that is stable and selective, with sensitivity to physiological concentrations of targeted analytes. We have combined glucose oxidase-modified carbon-fiber microelectrodes with fast-scan cyclic voltammetry for real-time measurements of glucose fluctuations in brain tissue. Work presented herein quantitatively compares three approaches to enzyme immobilization on the microelectrode surface-physical adsorption, hydrogel entrapment, and entrapment in electrospun nanofibers. The data suggest that each of these methods can be used to create functional microbiosensors. Immobilization of glucose oxidase by physical adsorption generates a biosensor with poor sensitivity to glucose and unstable performance. Entrapment of glucose oxidase in poly(vinyl alcohol) nanofibers generates microbiosensors that are effective for glucose measurements over a large linear range, and that may be particularly useful when targeting glucose concentrations in excess of 3 mm, such as in blood. Hydrogel entrapment is the most effective in terms of sensitivity and stability. These microbiosensors can be used for simultaneous monitoring of glucose and dopamine in real time. The findings outlined herein should be applicable to other oxidase enzymes, and thus they are broadly important for the development of new tools for real-time measurements of fluctuating molecules that are not inherently electroactive. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

The incidence of tinea pedis in diabetic versus nondiabetic patients with interdigital macerations: a prospective study.

PubMed

Legge, Bradford S; Grady, John F; Lacey, Autum M

2008-01-01

We sought to determine the incidence of tinea pedis in patients with otherwise asymptomatic pedal interdigital macerations. Both diabetic and nondiabetic populations were compared. Age and body mass index were also examined for their significance. Fungal cultures of skin scrapings from 80 patients (77 male and 3 female; mean age, 65 years) with interdigital macerations were performed; 40 patients had previously been diagnosed with type 2 diabetes and 40 did not have diabetes. Cultures revealed a 40% prevalence of tinea pedis in the total study population. The prevalence in the nondiabetic group was 37.5% and 42.5% for the diabetic group. This was not a statistically significant difference. Among patients with interdigital macerations that yielded positive fungal cultures, those in the nondiabetic group were 6.3 years older than those in the diabetic group. It was also observed that the nondiabetic patients with interdigital macerations yielding positive fungal cultures were 9.1 years older than patients with negative fungal cultures in the nondiabetic group. The results of this study provide the practitioner with a guide for treating pedal interdigital macerations. Because the likelihood of a tinea pedis infection is 40%, it seems prudent to treat these macerations with an antifungal agent. In regard to age, the results suggest that as nondiabetic patients age, the likelihood of an otherwise asymptomatic interdigital maceration yielding a positive fungal culture increases, and that diabetic patients may be susceptible to interdigital fungal infections at a younger age than those without diabetes.

Automated solar module assembly line

NASA Technical Reports Server (NTRS)

Bycer, M.

1980-01-01

The solar module assembly machine which Kulicke and Soffa delivered under this contract is a cell tabbing and stringing machine, and capable of handling a variety of cells and assembling strings up to 4 feet long which then can be placed into a module array up to 2 feet by 4 feet in a series of parallel arrangement, and in a straight or interdigitated array format. The machine cycle is 5 seconds per solar cell. This machine is primarily adapted to 3 inch diameter round cells with two tabs between cells. Pulsed heat is used as the bond technique for solar cell interconnects. The solar module assembly machine unloads solar cells from a cassette, automatically orients them, applies flux and solders interconnect ribbons onto the cells. It then inverts the tabbed cells, connects them into cell strings, and delivers them into a module array format using a track mounted vacuum lance, from which they are taken to test and cleaning benches prior to final encapsulation into finished solar modules. Throughout the machine the solar cell is handled very carefully, and any contact with the collector side of the cell is avoided or minimized.

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.

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

A miniature electronic nose system based on an MWNT-polymer microsensor array and a low-power signal-processing chip.

PubMed

Chiu, Shih-Wen; Wu, Hsiang-Chiu; Chou, Ting-I; Chen, Hsin; Tang, Kea-Tiong

2014-06-01

This article introduces a power-efficient, miniature electronic nose (e-nose) system. The e-nose system primarily comprises two self-developed chips, a multiple-walled carbon nanotube (MWNT)-polymer based microsensor array, and a low-power signal-processing chip. The microsensor array was fabricated on a silicon wafer by using standard photolithography technology. The microsensor array comprised eight interdigitated electrodes surrounded by SU-8 "walls," which restrained the material-solvent liquid in a defined area of 650 × 760 μm(2). To achieve a reliable sensor-manufacturing process, we used a two-layer deposition method, coating the MWNTs and polymer film as the first and second layers, respectively. The low-power signal-processing chip included array data acquisition circuits and a signal-processing core. The MWNT-polymer microsensor array can directly connect with array data acquisition circuits, which comprise sensor interface circuitry and an analog-to-digital converter; the signal-processing core consists of memory and a microprocessor. The core executes the program, classifying the odor data received from the array data acquisition circuits. The low-power signal-processing chip was designed and fabricated using the Taiwan Semiconductor Manufacturing Company 0.18-μm 1P6M standard complementary metal oxide semiconductor process. The chip consumes only 1.05 mW of power at supply voltages of 1 and 1.8 V for the array data acquisition circuits and the signal-processing core, respectively. The miniature e-nose system, which used a microsensor array, a low-power signal-processing chip, and an embedded k-nearest-neighbor-based pattern recognition algorithm, was developed as a prototype that successfully recognized the complex odors of tincture, sorghum wine, sake, whisky, and vodka.

An Interdigitated Coupler with Defect Ground Structure

DTIC Science & Technology

2015-07-01

branch-line coupler. In [8], DGS is used to microstrip forward-wave coupler for size–reduction. In fact, DGS have been widely used from the concept put...substantially. REFERENCE [1] Bialkowski M E, Seman N, Leong M S. Design of a compact ultra wideband 3 dB microstrip -slot coupler with high return losses and...Pozar D M. Microwave engineering. John Wiley & Sons, 2009. [4] You S J, Liao W. A multi-layer coupled-line power divider. Antennas , Propagation and EM

Organic vapor discrimination with chemiresistor arrays of temperature modulated tin-oxide nanowires and thiolate-monolayer-protected gold nanoparticles.

PubMed

Scholten, K; Bohrer, F I; Dattoli, E; Lu, W; Zellers, E T

2011-03-25

This paper explores the discrimination of organic vapors with arrays of chemiresistors (CRs) employing interface layers of tin-oxide nanowires (NWs) and thiolate-monolayer-protected gold nanoparticles (MPNs). The former devices use contact-printed mats of NWs on micro-hotplate membranes to bridge a pair of metal electrodes. Oxidation at the NW surface causes changes in charge transport, the temperature dependence of which differs among different vapors, permitting vapor discrimination. The latter devices use solvent cast films of MPNs on interdigital electrodes operated at room temperature. Sorption into the organic monolayers causes changes in film tunneling resistance that differ among different vapors and MPN structures, permitting vapor discrimination. Here, we compare the performance and assess the 'complementarity' of these two types of sensors. Calibrated responses from an NW CR operated at two different temperatures and from a set of four different MPN CRs were generated for three test vapors: n-hexane, toluene, and nitromethane. This pooled data set was then analyzed using principal components regression classification models with varying degrees of random error superimposed on the responses via Monte Carlo simulation in order to estimate the rates of recognition/discrimination for arrays comprising different combinations of sensors. Results indicate that the diversity of most of the dual MPN-CR arrays exceeds that of the dual NW-CR array. Additionally, in assessing all possible arrays of 4-6 CR sensors, the recognition rates of the hybrid arrays (i.e. MPN + NW) were no better than that of the 4-sensor array containing only MPN CRs.

Interdigital erosions - tinea pedis?

PubMed

Orgaz-Molina, Jacinto; Orgaz-Molina, Maria Carmen; Cutugno, Marilena; Arias-Santiago, Salvador

2012-10-01

Interdigital erosions are frequently due to tinea pedis. However, other infectious conditions, such as candidiasis, erythrasma or bacterial infections, can generate lesions that cannot be differentiated at the clinical level. Microbiological tests are therefore necessary. This clinical case shows a man with interdigital lesions of 10 months of evolution that are not responding to antifungal treatment.

Predicting plasmonic coupling with Mie-Gans theory in silver nanoparticle arrays

NASA Astrophysics Data System (ADS)

Ranjan, M.

2013-09-01

Plasmonic coupling is observed in the self-aligned arrays of silver nanoparticles grown on ripple-patterned substrate. Large differences observed in the plasmon resonance wavelength, measured and calculated using Mie-Gans theory, predict that strong plasmonic coupling exists in the nanoparticles arrays. Even though plasmonic coupling exists both along and across the arrays, but it is found to be much stronger along the arrays due to shorter interparticle gap and particle elongation. This effect is responsible for observed optical anisotropy in such arrays. Measured red-shift even in the transverse plasmon resonance mode with the increasing nanoparticles aspect ratio in the arrays, deviate from the prediction of Mie-Gans theory. This essentially means that plasmonic coupling is dominating over the shape anisotropy. Plasmon resonance tuning is presented by varying the plasmonic coupling systematically with nanoparticles aspect ratio and ripple wavelength. Plasmon resonance red-shifts with the increasing aspect ratio along the ripple, and blue-shifts with the increasing ripple wavelength across the ripple. Therefore, reported bottom-up approach for fabricating large area-coupled nanoparticle arrays can be used for various field enhancement-based plasmonic applications.

Tinea pedis acquired in mosques?

PubMed

Veraldi, Stefano; Esposito, Luigi; Gorani, Alberto

2018-03-30

Interdigital tinea pedis is a mycotic infection of the feet which occurs mainly in adult males. The transmission is due to repeated contacts with the soil. In Italy, Trichophyton rubrum, T. mentagrophytes (including T. mentagrophytes var. interdigitale) and Epidermophyton floccosum are the most frequently involved species. Interdigital tinea pedis is characterized clinically by maceration, erythema, vesicles, scales, crusts, erosions and ulcers located at the 2 nd , 3 rd and 4 th interdigital folds. Interdigital tinea pedis may be asymptomatic; however, when erosions and ulcers occur, the patients may complain of pruritus, burning sensation and pain. Superinfections, caused by Candida albicans and Gram-negative bacteria, are not rare. 1 We present four cases of interdigital tinea pedis which was probably acquired in Turkish mosques and holy Muslim places. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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.

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.

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.

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

NASA Astrophysics Data System (ADS)

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

2004-12-01

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

Optical-Microwave Interactions in Semiconductor Devices.

DTIC Science & Technology

1981-03-01

Interdigital Photoconductors ( IDPC ) ......... ..... 112 G. Conclusions.. ....... .. 120 6 CONCLUSIONS AND RECOMMENDATIONS FOR FUTURE WORK . 121...The detector developed at the Hughes Research Laboratories ( IDPC ) involves placing an interdigital metal electrode 53- 5 5 structure on top of a F...easier to perform with the IDPC detector. We believe the interdigital photoconductive detector has many advantages over existing detectors. First, the

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.

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.

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

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.

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

Composite wire microelectrode and method of making same

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

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

1996-12-03

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

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

EPA Science Inventory

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

Sensitivity improvement of an electrical sensor achieved by control of biomolecules based on the negative dielectrophoretic force.

PubMed

Kim, Hye Jin; Kim, Jinsik; Yoo, Yong Kyoung; Lee, Jeong Hoon; Park, Jung Ho; Hwang, Kyo Seon

2016-11-15

Effective control of nano-scale biomolecules can enhance the sensitivity and limit of detection of an interdigitated microelectrode (IME) sensor. Manipulation of the biomolecules by dielectrophoresis (DEP), especially the negative DEP (nDEP) force, so that they are trapped between electrodes (sensing regions) was predicted to increase the binding efficiency of the antibody and target molecules, leading to a more effective reaction. To prove this concept, amyloid beta 42 (Aβ42) and prostate specific antigen (PSA) protein were respectively trapped between the sensing region owing to the nDEP force under 5V and 0.05V, which was verified with COMSOL simulation. Using the simulation value, the resistance change (ΔR/Rb) of the IME sensor from the specific antibody-antigen reaction of the two biomolecules and the change in fluorescence intensity were compared in the reference (pDEP) and nDEP conditions. The ΔR/Rb value improved by about 2-fold and 1.66-fold with nDEP compared to the reference condition with various protein concentrations, and these increases were confirmed with fluorescence imaging. Overall, nDEP enhanced the detection sensitivity for Aβ42 and PSA by 128% and 258%, respectively, and the limit of detection improved by up to 2-orders of magnitude. These results prove that DEP can improve the biosensor's performance. Copyright © 2016 Elsevier B.V. All rights reserved.

Miniaturised enzymatic conductometric biosensor with Nafion membrane for the direct determination of formaldehyde in water samples.

PubMed

Nguyen-Boisse, Thanh-Thuy; Saulnier, Joëlle; Jaffrezic-Renault, Nicole; Lagarde, Florence

2014-02-01

A new conductometric enzyme-based biosensor was developed for the determination of formaldehyde (FA) in aqueous solutions. The biosensor was prepared by cross-linking formaldehyde dehydrogenase from Pseudomonas putida with bovine serum albumin in saturated glutaraldehyde vapours (GA) at the surface of interdigitated gold microelectrodes. Nicotinamide adenine dinucleotide cofactor (NAD(+)) was added in solution at each measurement to maintain enzyme activity. Addition of a Nafion layer over the enzyme modified electrode resulted in a significant increase of biosensor signal due to enhanced accumulation of protons generated by enzymatic reaction at the electrode surface. Different parameters affecting enzyme activity or playing a role in ionic transfer through the Nafion membrane were optimised. In optimal conditions (0.045 mg enzyme, 30 min exposure to GA, 0.3 μL of a 1% (v/v) Nafion solution deposit, measurement in 5 mM phosphate buffer pH 7 containing 20 μM NAD(+)), the biosensor signal was linear up to 10 mM FA, and the detection limit was 18 μM. Relative standard deviations calculated from five consecutive replicates of FA solutions were lower than 5% in the 1-10 mM range. The biosensor was successfully applied to the determination of FA in spiked water samples (tap water and Rhone river water), with recoveries in the 95-110% range.

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.

Simulations and design of microfabricated interdigitated electrodes for use in a gold nanoparticle enhanced biosensor.

PubMed

Hermansen, Peter; MacKay, Scott; Wishart, David; Jie Chen

2016-08-01

Microfabricated interdigitated electrode chips have been designed for use in a unique gold-nanoparticle based biosensor system. The use of these electrodes will allow for simple, accurate, inexpensive, and portable biosensing, with potential applications in diagnostics, medical research, and environmental testing. To determine the optimal design for these electrodes, finite element analysis simulations were carried out using COMSOL Multiphysics software. The results of these simulations determined some of the optimal design parameters for microfabricating interdigitated electrodes as well as predicting the effects of different electrode materials. Finally, based on the results of these simulations two different kinds of interdigitated electrode chips were made using photolithography.

Arrays of Ultrathin CdS Nanoflakes with High-Energy Surface for Efficient Gas Detection.

PubMed

Liu, Xiao-Hua; Yin, Peng-Fei; Kulinich, Sergei A; Zhou, Yu-Zhu; Mao, Jing; Ling, Tao; Du, Xi-Wen

2017-01-11

It is fascinating and challenging to endow conventional materials with unprecedented properties. For instance, cadmium sulfide (CdS) is an important semiconductor with excellent light response; however, its potential in gas-sensing was underestimated owing to relatively low chemical activity and poor electrical conductivity. Herein, we demonstrate that an ideal architecture, ultrathin nanoflake arrays (NFAs), can improve significantly gas-sensing properties of CdS material. The CdS NFAs are grown directly on the interdigitated electrode to expose large surface area. Their thickness is reduced below the double Debye length of CdS, permitting to achieve a full depletion of carriers. Particularly, the prepared CdS nanoflakes are enclosed with high-energy {0001} facets exposed, which provides more active sites for gas adsorption. Moreover, the NFAs exhibit the light-trapping effect, which further enhances their gas sensitivity. As a result, the as-prepared CdS NFAs demonstrate excellent gas-sensing and light-response properties, thus being capable of dual gas and light detection.

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.