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1
Fofonoff, Timothy Andrew 1977. "Brain microelectrode array systems." Thesis, Massachusetts Institute of Technology, 2003. http://hdl.handle.net/1721.1/41031.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2003.Includes bibliographical references (leaves 110-114).
New methods for manufacturing microelectrode array assemblies, passive devices designed for intracortically recording brain activity in nonhuman primates, were developed and explored. Wire electrical discharge machining (EDM), chemical etching, micromilling, parylene deposition, and laser ablation were some of the processes employed to create distinctive microstructures with fine features and high aspect ratios. These microstructures, constructed from a variety of metals and polymers, were assembled to form the mechanical front end of a brain-machine interface (BMI). The developed techniques were used to produce microelectrode array assemblies for the Telemetric Electrode Array System (TEAS), a surgically implantable wireless device to be used for motor cortex studies in nonhuman primates. Two prototypes of the TEAS microelectrode array assemblies were implanted in animals in order to validate the design and the manufacturing processes. Neural activity was successfully recorded. Future work is required in order to refine and further automate the processes. Similar devices could one day develop into neural prostheses for clinical use by outputting motor intent captured from brain activity in paralyzed patients.
by Timothy Andrew Fofonoff.
S.M.
2
Delcourt-Lancon, Alice. "Electrochemical analysis supported by macro and microelectrode array." Thesis, Durham University, 2011. http://etheses.dur.ac.uk/3570/.
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The purpose of this project was to investigate cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) analytical techniques for enantioselective sensing at both a macroelectrode and a microelectrode array. The scale of the electrochemical cell was reduced from macro to micro dimensions to improve both the electroanalytical detection and the efficient use of chemicals. A microdevice was fabricated using photolithography and plasma bonding and consisting of a microelectrode array (MEA) of 306 microelectrodes, each with a diameter of 45 µm supported by a polydimethylsiloxane (PDMS) slab engraved with microfluidic channels. The electroanalytical performances of the microdevice were characterised using cyclic voltammetry and it was established that the metallisation process influenced the surface roughness of the electrode, and also affected the final response of the array. The microdevice was used for flow injection analysis using chronoamperometry and provided the capability to detect small changes of analyte concentration. The selective electro-oxidation of phenylethanol catalysed by TEMPO and (-)-sparteine at a macroelectrode and MEA was investigated. The CV analysis showed a reproducible selective oxidation in favour of the (-)-phenylethanol enantiomer. The performances of the electrodes were enhanced to improve their enantioselective capability, and to extend their application to biosensors by functionalising their surface with Self-Assembled Monolayers (SAM). The electrodes were modified with glutathione and cysteine chiral molecules to investigate their ability to recognise the proline enantiomers using EIS analysis. The electron transfer rate of the ferricyanide analyte at the cysteine monolayer was less in the presence of D proline than it was in the presence of L-proline, indicating the selective penetration of the enantiomer through the monolayer. The properties of the macroelectrode and MEA were extended to biological applications by modifying their surfaces with thiolated single stranded DNA.
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Bhat, Ashwini. "MEASURING IMPEDANCE OF TISSUES USING A MICROFABRICATED MICROELECTRODE ARRAY." DigitalCommons@CalPoly, 2012. https://digitalcommons.calpoly.edu/theses/908.
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MEASURING IMPEDANCE OF TISSUES USING A MICROFABRICATED MICROELECTRODE ARRAY By Ashwini Bhat
This thesis looks at the possibility of using impedance spectroscopy for differentiating tissue, using a microelectrode array (MEA). The thesis first discusses the background and the motivation for this thesis. It covers the certain basic concepts of the human skin starting from the top epidermis layer all the way to the deep dermis layers of the skin. Then it discusses different types of skin cancer and how they occur, in humans. It also discusses various microfabrication techniques such as oxidation, wet etching, sputtering and photolithography for the creation of a MEA in order to test the tissue. The microfabricated MEA is then used to measure impedance across cooked and raw chicken at different frequencies in order to see if the two types of tissues can be differentiated using their respective impedances. The data shows that the MEA was not able to successfully differentiate the two types of the tissues. It does however list multiple improvements in the fabrication of the MEA and improvements that could be made to the testing procedures which could possible give greater difference in impedance between the two tissues
4
Clark, James. "Microelectrode array fabrication for electrochemical detection with carbon nanotubes." Thesis, University of Surrey, 2016. http://epubs.surrey.ac.uk/811032/.
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Understanding how the brain works remains one of the key challenges for scientists. To further this understanding a wide variety of technologies and research methods have been developed. One such technology is conductive electrodes, used to measure the electrical signals elicited from neuronal cells and tissues. These electrodes can be fabricated as a singular electrode or as a multi-electrode array (MEA). This permits bio-electrical measurements from one particular area or simultaneous measurements from multiple areas, respectively. Studying electrical and chemical signals of individual cells in situ requires the use of electrodes with ≤20 µm diameter. However, electrodes of this size generally produce high impedance, perturbing recording of the small signals generated from individual cells. Nanomaterials, such as carbon nanotubes (CNTs), can be deposited to increase the real surface area of these electrodes, producing higher sensitivity measurements. This thesis investigates the potential for using photo-thermal chemical vapour deposition grown CNTs as the electrode material for a de novo fabricated MEA. This device aimed to measure electrochemical signals in the form of dopamine, an important mammalian neurotransmitter, as well as conventional bio-electrical signals that the device is designed for. Realising this aim began with improving CNT aqueous wetting behaviour via oxygen plasma functionalisation. This procedure demonstrated grafting of oxygen functional groups to the CNT structure, and dramatic improvements in aqueous wetting behaviour, with CNTs attached to the device. Subsequently, oxygen plasma functionalised CNT-based MEAs were fabricated and tested, allowing comparisons with a non-functionalised CNT MEA and a state-of-the-art commercial MEA. The functionalised CNT MEA demonstrated an order of magnitude improvement compared to commercial MEAs (2.75 kΩ vs. 25.6 kΩ), at the biologically relevant frequency of 1 kHz. This was followed by measurement of one of the best sensitivity density values, compared to the available literature, for the electrochemical detection of dopamine (9.48 µA µM-1 mm-2). The functionalised CNT MEA then illustrated some selectivity compared to common interferents, i.e. ascorbic acid, of a higher concentration. Nonetheless, imaging of the MEA revealed CNTs were being removed from the electrode areas due to extensive use. Therefore, the final results chapter aimed to develop a novel fabrication route for CNT-based MEAs that produced improved CNT retention on the electrodes. This next-generation functionalised CNT-based MEA displayed improved CNT retention, whilst also producing competitive electrochemical impedance values at 1 kHz (17.8 kΩ) and excellent electrochemical selectivity for dopamine vs. ascorbic acid. Overall, this thesis demonstrates the potential for using MEAs as electrochemical detectors of biological molecules, specifically when using functionalised CNTs as the electrode material.
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Schwartz, Jacob C. "Functional and Categorical Analysis of Waveshapes Recorded on Microelectrode Arrays." Thesis, University of North Texas, 2005. https://digital.library.unt.edu/ark:/67531/metadc4746/.
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Dissociated neuronal cell cultures grown on substrate integrated microelectrode arrays (MEAs) generate spontaneous activity that can be recorded for up to several weeks. The signature wave shapes from extracellular recording of neuronal activity display a great variety of shapes with triphasic signals predominating. I characterized extracellular recordings from over 600 neuronal signals. I have preformed a categorical study by dividing wave shapes into two major classes: (type 1) signals in which the large positive peak follows the negative spike, and (type 2) signals in which the large positive peak precedes the negative spike. The former are hypothesized to be active signal propagation that can occur in the axon and possibly in soma or dendrites. The latter are hypothesized to be passive which is generally secluded to soma or dendrites. In order to verify these hypotheses, I pharmacologically targeted ion channels with tetrodotoxin (TTX), tetraethylammonium (TEA), 4-aminopyridine (4-AP), and monensin.
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McEwan, Carolyn Audrey. "Stimulation of human neuroblastoma cells using a planar microelectrode array." Thesis, University of Glasgow, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343915.
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WEI, XINGTAO. "SILICON MICROELECTRODE ARRAYS FOR IN SITU ENVIRONMENTAL MONITORING." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1123783607.
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Choi, Yoonsu. "A Three-Dimensional Coupled Microelectrode and Microfluidic Array for Neuronal Interfacing." Diss., Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/11638.
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The objective of this research is to develop a three-dimensional (3-D) microfluidic/ electronic interface system for sustaining and monitoring 3-D neuronal networks. This research work is divided into two parts. One is the development of a 3-D multi-electrode array (MEA) with integrated microfluidic channels. The other is a microneedle array with embedded microelectrodes and microfluidic channels.
The 3-D MEA is composed of three elements that are essential for the development and monitoring of 3-D cultures of neurons. These components consist of scaffolds for cellular growth and structural stability, microfluidic channels for cell maintenance and chemical stimulation, and electrodes for electrical stimulation and recording. Two kinds of scaffold structures have been fabricated. The first scaffolding scheme employs a double exposure technique that embeds SU-8 towers into an SU-8 substrate. The second scaffolding mechanism introduces interconnects between towers for the purpose of mechanically supporting 3-D cell cultures and facilitating 3-D synaptic connections. Microfluidic channels are combined for fine control of the cellular microenvironment by means of diffusive and convective fluidic processes. Hollow towers with three-layer side ports were developed by using double exposure techniques and excimer laser ablation. The electrodes are combined into an integrated system that is capable of monitoring electrical activities and the cellular impedances of neurons which are attached to the electrodes.
The second part of this research is to fabricate a microneedle array for monitoring brain slices, which will directly detect electrical signals from living brain slices. Although the microneedle array is targeting different 3-D neuronal networks, it also has three components and the fabrication steps are the same as those for the 3-D MEA. To generate the sharp tip, isotropic reactive ion etching (RIE) is performed on tapered SU-8 towers. High aspect ratio tower structures can be effectively generated with SU-8 and tapered shapes are created by backside exposure.
The resulting systems will enable a new field of neurobiological research, in which the collective properties of 3-D neuronal circuits can be observed and manipulated with unprecedented detail and precision, and at a level of control not possible in living animals.
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Choi, Yoonsu. "A three-dimensional copuled microelectrode and microfluidic array for neuronal interfacing." Available online, Georgia Institute of Technology, 2005, 2005. http://etd.gatech.edu/theses/available/etd-05202005-103249/.
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Thesis (Ph. D.)--Electrical and Computer Engineering, Georgia Institute of Technology, 2006.Michaels, Thomas E., Committee Member ; LaPlaca, Michelle, Committee Member ; Frazier, A. Bruno, Committee Member ; DeWeerth, Stephen P., Committee Member ; Allen, Mark G., Committee Chair.
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Maghribi, Mariam Nader. "Microfabrication of an implantable silicone microelectrode array for an epiretinal prosthesis /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2003. http://uclibs.org/PID/11984.
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Maghribi, M. "Microfabrication of an Implantable silicone Microelectrode array for an epiretinal prosthesis." Washington, D.C : Oak Ridge, Tenn. : United States. Dept. of Energy ; distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2003. http://www.osti.gov/servlets/purl/15005780-5uYpbJ/native/.
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Thesis (Ph.D.); Submitted to the Univ. of California, Davis, CA (US); 10 Jun 2003.Published through the Information Bridge: DOE Scientific and Technical Information. "UCRL-LR-153347" Maghribi, M. 06/10/2003. Report is also available in paper and microfiche from NTIS.
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Draper, Neil. "Microfabrication of Bio-Analytical Devices: Microelectrode Array and Traveling-Wave Electrophoresis." DigitalCommons@USU, 2015. https://digitalcommons.usu.edu/etd/4032.
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The need for potable water is increasing with the ever-increasing world population. Further development of fast, portable, and cost effective analytical tools is necessary in order to create diagnostic techniques capable of supporting the water needs of the world’s population. Within the last decade microfluidics and Lab-on-a-Chip (LOC) technologies have increased the portability and speed of detection for aqueous samples. Photolithography techniques serve as a cost effective fabrication tool to create LOC electrodes on the micron scale.
An in-depth look at the fabrication process is undertaken in this paper in order to further the development of micro-scale detection techniques. An electrode array capable of detecting multiple targets within one aqueous sample was designed and fabricated. The electrode array was assessed for performance characteristics to determine if reproducibility is possible. The fabrication process was also detailed for a new chemical separation technique, traveling-wave electrophoresis (TWE). TWE could serve as a separation tool capable of separating out specific charged molecules for biological and chemical samples. The TWE device was assessed on the capabilities to move charged molecules.
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Gardner, Robert D. "Development of a Microelectrode Array Sensing System for Water Quality Monitoring." DigitalCommons@USU, 2008. https://digitalcommons.usu.edu/etd/648.
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This thesis reports the design and fabrication of a low-cost reliable microelectrode array sensing platform and its application toward water quality monitoring, including heavy metal ion detection. Individually addressable microelectrodes were designed in a planar array on a nonconductive glass substrate by a photolithography method. The size, shape, composition, and functionality of the microelectrodes were theoretically explored in order to maximize performance. The microelectrode array sensing platform was proven and characterized in the K3Fe(CN)6 electrochemical standard using cyclic voltammetry. The sensor platform exhibited well defined voltammograms and had increased sensitivity relative to a commercially available microelectrode of similar size. Feasibility for application to heavy metal ions, copper and lead, detection in aqueous solutions was demonstrated utilizing the electrochemical method of anodic stripping voltammetry. Well defined voltammograms for the copper and lead ions were obtained with individual microelectrodes of the sensor platform, and compared against the similar sized commercially available microelectrode; increased sensitivity was observed.
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Mills, Daniel W. "Towards a commerical microelectrode array based sensor for improved chlorine detection." Thesis, Cranfield University, 2005. http://dspace.lib.cranfield.ac.uk/handle/1826/4177.
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The commercial development of a disposable aqueous chlorine sensor based on a novel microelectrode array fabrication process is described. Non-conducting poly(o-phenylenediamine) films are firstly used to passivate conductive surfaces. Ultrasonic ablation of passivated electrode assemblies then results in the formation of a plurality of wells to expose the underlying conductive substrate, thereby forming a microelectrode array. Microelectrode arrays produced in this manner can be exploited within many electrochemical sensing applications; however, portable aqueous chlorine detection has been selected by Microarray Limited (the industrial sponsors of this project) as a primary vehicle for launching its generic production technology. The scale of microelectrode array production has been extended from that of individual gold sputtercoated glass slide electrodes - to the simultaneous production of hundreds of low-cost screen printed carbon-ink based sensors. A focus has been directed at all stages towards permitting the cost-effective large-scale mass production of sensors with a view to challenging existing portable aqueous chlorine measurement technologies both in terms of performance and unit cost. Based on volume batches of 250,000, it has been calculated that Microarray Limited sensors can be manufactured for a unit cost of approximately 2.5 pence, sufficiently low to provide scope for a competitive yet profitable sale price. The Microarray Limited aqueous chlorine detection system has improved the limit of detection from 0.01 ppm to 0.005 ppm total chlorine without sacrificing accuracy. Furthermore, this novel approach to aqueous chlorine detection offers numerous key benefits to the customer including reduced testing time, a more straightforward operation and the elimination of harmful reagents. Product development has been described from an initial concept through to a pre-production phase. The development of an innovative generic sensor packaging technology is also described.
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Naughton, Jeffrey R. "Neuroelectronic and Nanophotonic Devices Based on Nanocoaxial Arrays." Thesis, Boston College, 2017. http://hdl.handle.net/2345/bc-ir:108037.
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Thesis advisor: Michael J. NaughtonThesis advisor: Michael J. Burns
Recent progress in the study of the brain has been greatly facilitated by the development of new measurement tools capable of minimally-invasive, robust coupling to neuronal assemblies. Two prominent examples are the microelectrode array, 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. Herein, 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
Thesis (PhD) — Boston College, 2017
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Physics
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Seo, Cheong Soo. "Electromechanics of dielectric particles in dielectric liquids acted on by a microelectrode array." Texas A&M University, 2005. http://hdl.handle.net/1969.1/3301.
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Arrays of microelectrodes were used to apply forces to dielectric (soda lime glass)
spheres in a thin (200 micrometer thick) layer of a dielectric liquid polymer (EOPN
8021). The microelectrodes were fabricated using standard photolithographic methods of
evaporating and electroplating gold onto a glass substrate. The objective is to use the
electric body forces in the sphere and the electric surface tractions on the sphere to
position the spheres in a microscale pattern, in this case a square array in-plane.
Three sizes of spheres were used: 30, 90, and 170 microns in diameter. The 30
micron spheres formed clusters associated with the regions of highest electric energy
density, whereas single 90 micron spheres were located at the regions of highest electric
energy density. The 170 micron spheres generally did not form patterns. The
experiments indicated that free charges, either in the volume of the sphere and/or on the
sphere surface, significantly influence the motion of the sphere.
A finite element analysis was performed to study the electro-fluid mechanics.
The liquid velocity and streamlines were plotted, and the force resultants due to the
liquid acting on the sphere were calculated. Also, the electric body force and surface tractions resultants were calculated. In general, the forces on the sphere and the liquid
velocity are in agreement with the experimental results.
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Lee, Jin-Hwan. "MEMS Needle-Type Multi-Analyte Microelectrode Array Sensors for In Situ Biological Applications." University of Cincinnati / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1212146149.
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Santa, Maria Cara L. "Optimization of Cell Culture Procedures for Growing Neural Networks on Microelectrode Arrays." Thesis, University of North Texas, 2007. https://digital.library.unt.edu/ark:/67531/metadc5126/.
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This thesis describes the development of an optimized method for culturing dissociated, monolayer neuronal networks from murine frontal cortex and midbrain. It is presented as a guidebook for use by cell culture specialists and laboratory personnel who require updated and complete procedures for use with microelectrode array (MEA) recording technology. Specific cell culture protocols, contamination prevention and control, as well common problems encountered within the cell culture facility, are discussed. This volume offers value and utility to the rapidly expanding fields of MEA recording and neuronal cell culture. Due to increasing interest in determining the mechanisms underlying Parkinson's disease, the newly developed procedures for mesencephalon isolation and culture on MEAs are an important research contribution.
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Heid, Andreas [Verfasser], and David [Akademischer Betreuer] Wharam. "Buildup and Characterization of an Active Flexible Microelectrode Array / Andreas Heid ; Betreuer: David Wharam." Tübingen : Universitätsbibliothek Tübingen, 2020. http://d-nb.info/1213720575/34.
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Rutherford, Erin Cathleen. "MICROELECTRODE ARRAY RECORDINGS OF L-GLUTAMATE DYNAMICS IN THE BRAINS OF FREELY MOVING RATS." UKnowledge, 2007. http://uknowledge.uky.edu/gradschool_diss/523.
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L-glutamate (Glu) is the predominant excitatory neurotransmitter inthe mammalian central nervous system (CNS) and is associated with a widevariety of functions including motor behavior and sensory perception. Whilemicrodialysis methods have been used to record tonic levels of Glu, little isknown about the more rapid changes in Glu signals that may occur in awakeanimals. We have previously reported acute recording methods using anenzyme-based microelectrode array (MEA) with fast temporal resolution (800msec), that is minimally invasive and is capable of detecting low levels of Glu (andlt;0.2 ??M) in anesthetized animals with little interference from other analytes. Wehave made a series of modifications to the MEA design to allow for reliablemeasures in the brain of awake behaving rats. In these studies, wecharacterized the effects of chronic implantation of the MEA into the striatum andprefrontal cortex (PFC) of Fischer 344 and Long Evans rats. We measuredresting levels of Glu and local application of Glu for 7 days without a significantloss of sensitivity and determined that Glu measures due to exogenous Gluvaried between rat strain and brain region. In addition, we determined theviability of the recordings in the brains of awake animals. We performed studiesof tail-pinch induced stress which caused an increase in Glu in the striatum andPFC of Long Evans and Fischer 344 rats. Histological data show that chronicimplantation of our MEAs caused minimal injury to the CNS. Taken together, ourdata support that chronic recordings of tonic and phasic Glu can be carried out inawake rats reliably for 7 days in vivo allowing for longer term studies of Gluregulation in behaving rats.
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Talei, Franzesi Giovanni. "A novel polymeric microelectrode array for highly parallel, long-term neuronal culture and stimulation." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/43878.
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Thesis (M. Eng.)--Harvard-MIT Division of Health Sciences and Technology, 2008.Includes bibliographical references (leaves 51-56).
Cell-based high-throughput screening is emerging as a disruptive technology in drug discovery; however, massively parallel electrical assaying of neurons and cardiomyocites has until now been prohibitively expensive. To address this limitation, we developed a scalable, all-organic 3D microelectrode array technology. The cheap, disposable arrays would be integrated into a fixed stimulation and imaging setup, potentially amenable to automated handling and data analysis. A combination of activity-dependent plasticity, made possible by independent control of up to 64 stimulating electrodes, and, eventually, of substrate chemical patterning would be employed to constrain the neuronal culture network connectivity. In order to ensure longterm survival of the cultures, a bottom feeder layer of glial cells would be grown. In addition to high-throughput screening application, the polymeric microelectrode arrays and integrated stimulation systems were designed to allow the long-term study of synaptic plasticity, combining excellent long-term culture capabilities with a unique ability to independently control each electrode stimulation pattern. The resulting activity could be monitored optically, e,g, with calcium or voltage sensitive dyes, and the images could be stored and processed (possibly even in real time) within the same environment (LabView) as the stimulator. To fabricate the polymeric microelectrode array, we prepare a multilayered mask substrate, by reversibly bonding together two sheets of implant-grade polydimethylsiloxane (PDMS) sheets, with or without a glass coverslip between them. Thanks to PDMS self-adhesive properties the various layers are held together stably but reversibly. The mask is then laser-patterned, using either a standard CO2 laser or a 193 nm excimer laser.
(cont.) The mask can then be adhered onto a glassy carbon or ITO electrode, and polypyrrole, doped with either hyaluronic acid or sodium dodecylbenzesulfonic acid, can be electrodeposited through it. Finally, the construct is removed from the deposition bath and the upper, sacrificial mask layer carefully peeled away. This fabrication method allows exquisite control overall 3D electrode geometry, is suitable to produce structures between one and several hundred micrometers in diameter, either filled or tubular, and scales extremely well, so that, for example, 384 by 64 electrodes arrays can be patterned in just a few minutes and grown in the same time as a single array.
by Giovanni Talei Franzesi.
M.Eng.
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Day, Brian Keith. "MICROELECTRODE ARRAY STUDIES OF NORMAL AND DISEASE-ALTERED L-GLUTAMATE REGULATION IN THE MAMMALIAN CENTRAL NERVOUS SYSTEM." UKnowledge, 2005. http://uknowledge.uky.edu/gradschool_diss/235.
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L-glutamate (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system. Monitoring extracellular Glu is critical to understanding Glu regulation to discriminate physiological and pathological roles. To overcome the limitations of previous in vivo extracellular Glu studies, we developed Glu selective microelectrode arrays with better spatial and temporal resolutions than commonly used techniques like microdialysis. We used these microelectrode arrays to characterize basal and potassium-evoked Glu neurotransmission in the normal rat brain. We then investigated disease-related Glu alterations in a rat model of Parkinson's disease and normal Glu regulation in young and aged rhesus monkeys. In the normal anesthetized rat striatum and frontal cortex, basal Glu was regulated by active release and uptake mechanisms, fully TTX-dependent, and measured at ~2 micromolar levels. Potassium-evoked Glu kinetics were fast, concentration-dependent, and rapidly reproducible at 15-20 seconds intervals. In the unilateral 6-hydroxydopamine-lesioned rat, there were significant bilateral increases in potassium-evoked Glu release in the striatum and frontal cortex compared to hemisphere-matched non-lesioned rats. Ipsilateral striatal effects may have been related to DA loss, while contralateral striatal effects and the bilateral frontal corticaleffects may have resulted from parkinsonian neurotransmitter changes or bilateral neuranatomical connectivity, especially in the cortex. There were also alterations in Glu kinetics in the nucleus accumbens in both non-lesioned and lesioned rats. With appropriate technological and methodological modifications, we successfully recorded normal Glu signaling in anesthetized nonhuman primates in the operating room. Fast potassium-evoked Glu signals were recorded in the motor cortex of all monkeys, and Glu ejections showed robust Glu uptake in the motor and frontal cortices of all monkeys. These findings are comparable to initial rat studies. Slow evoked Glu kinetics and high basal Glu levels with oscillatory behavior were recorded in the frontal cortex. The primary age-related differences between monkeys were the nearly ten-fold increases in the volumes of Glu ejected needed in the aged monkey to achieve amplitude-matched signals in the motor and frontal cortices and a decreased uptake rate in the motor cortex. Preliminary work with excised human tissue and future plans for patient-oriented research and clinical applications are discussed.
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DiLorenzo, Daniel John. "Development of a chronically implanted microelectrode array for intraneural electrical stimulation for prosthetic sensory feedback." Thesis, Massachusetts Institute of Technology, 1999. http://hdl.handle.net/1721.1/9329.
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Thesis (S.M.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 1999.Includes bibliographical references (leaves 42-44).
The functionality of prosthetic limbs is restricted by the limited availability of sensory feedback. This research aims to develop a technology to allow the presentation of sensory information directly to the sensory afferent neurons of the transected peripheral nerve in the stump of the amputee. lntraneural implants of several designs were developed and implanted in rabbit animal models and monitored for chronic functionality evaluated using both neurophysiological and behavioral tests. Animal studies have demonstrated single channel implant functionality of up to 129 days. The relative merit of the designs is assessed, and future directions for implant design and behavioral testing are suggested.
by Daniel DiLorenzo.
S.M.
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Sörensen, Sören Per. "Development of a cell-based drug screening platform : extracellular recording and electrochemical impedance spectroscopy on microelectrode array chips." Thesis, University of Bath, 2007. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486476.
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Two established methods, Electrochemical Impedance Spectroscopy (EIS) and extracellular recording, were implemented into a technology platform for non-invasive whole-cell biosensing. Electrical activity of cardiomyocytes and cell-substrate interaction of human ovarian cancer cells was monitored on electrode array chips. The performance of cells inside a microfluidic or closed low volume environment was investigated. Prior to the development of the entire microfluidic platform the two transducing methods were evaluated in single experiments. Processes as cellular attachment and detachment were monitored using EIS and single frequency impedance sensing. Electrodes of different size and structure were employed and compared for their impedance response. It was shown that small electrodes (A = 9·10-6 cm²) are more sensitive to cell-substrate interaction than larger ones (A = 9·10-5 cm²) and that the frequency used for analysis has a profound influence on the sensitivity. Data were modelled using a common equivalent circuit that represents a cell layer on an electrode resulting in an increase of the impedance magnitude by <170 % due to cell attachment. In order to demonstrate the potential of this method for biomedical applications, experiments related to anti-cancer strategies were performed. Cell detachment was induced by addition of synthetic integrin ligands and by hypericin mediated photodynamic therapy and monitored with impedance-based biosensing. Electrical activity of cardiomyocytes cultured on microelectrode arrays was monitored inside a microfluidic system. The chronotropic drug isoproterenol was applied using a robotic dispensing machine, and the resulting changes in spike rate and duration were compared with results gained by experiments with a large scale MEA chip. The experimental findings inspired the development of a technology platform that was finally evaluated by monitoring extracellular signals from myocytes in response to Isoproterenol. Another topic was the comparison of cell-substrate interaction monitored on various electrode structures.
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Mattinson, Catherine Elizabeth. "DYNAMIC L-GLUTAMATE SIGNALING IN THE PREFRONTAL CORTEX AND THE EFFECTS OF METHYLPHENIDATE TREATMENT." UKnowledge, 2012. http://uknowledge.uky.edu/neurobio_etds/4.
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The prefrontal cortex (PFC) is an area of the brain that is critically important for learning, memory, organization, and integration, and PFC dysfunction has been associated with pathologies including Alzheimer’s disease, schizophrenia, and drug addiction. However, there exists a paucity of information regarding neurochemical signaling in the distinct sub-regions of the PFC, particularly the medial prefrontal cortex (mPFC). The mPFC receives glutamatergic input from a number of brain areas, and functional glutamate signaling is essential for normal cognitive processes. To further understand glutamate neurotransmission, in vivo measurements of glutamate were performed in the cingulate cortex, prelimbic cortex, and infralimbic cortex of anesthetized rats using enzyme-based microelectrode array technology. Measurements of acetylcholine were also performed to examine the relationship between glutamate and other neurotransmitters in the mPFC. The described studies revealed a homogeneity of glutamate and acetylcholine signaling in the mPFC sub-regions, indicating somewhat uniform tonic and phasic levels of these two transmitters. In the infralimbic mPFC of awake freely-moving rats, rapid, phasic glutamate signaling events, termed “transients” were observed and in vivo glutamate signaling was successfully monitored over 24 hour time periods.
The effects of methylphenidate (MPH), a stimulant medication with abuse potential that is used in the treatment of attention-deficit hyperactivity disorder, were measured in mPFC sub-regions of anesthetized rats. Data revealed similar tonic and phasic glutamate levels between chronic MPH-treated rats and controls in all sub-regions. Locomotor data from the chronic treatment period supported the behavioral sensitization effects of multiple MPH treatments. Significant effects were observed in locomotor activity, resting levels of glutamate, and glutamate uptake rates in the infralimbic mPFC of awake, freely-moving animals that received chronic MPH treatment.
Taken together, this body of work characterizes glutamate signaling in the rat mPFC to a degree never before reported, and serves to report for the first time the effects of MPH on glutamate signaling in the mPFC.
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DO, JAEPHIL. "A DISPOSABLE POLYMER LAB-ON-A-CHIP WITH MICRO/NANO BIOSENSOR FOR MAGNETIC NANO BEAD-BASED IMMUNOASSAY." University of Cincinnati / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1164035684.
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Guvanasen, Gareth Sacha. "Stretchable microneedle electrode array for stimulating and measuring intramuscular electromyographic activity." Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/54392.
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The advancement of technologies that interface with electrically excitable tissues, such as the cortex and muscle, has the potential to lend greater mobility to the disabled, and facilitate the study of the central and peripheral nervous systems. Myoelectric interfaces are currently limited in their signal fidelity, spatial resolution, and interfacial area. Such interfaces are either implanted in muscle or applied to the surface of the muscle or skin. Thus far, the former technology has been limited in its applications due to the stiffness (several orders of magnitude greater than muscle) of its substrates, such as silicon and polyimide, whereas the latter technology suffers from poor spatial resolution and signal quality due to the physical separation between the electrodes and the signal source. We have developed a stretchable microneedle electrode array (sMEA) that can function while stretching and flexing with muscle tissue, thereby enabling multi-site muscle stimulation and electromyography (EMG) measurement across a large interfacial area.
The scope of this research encompassed: (i) the development of a stretchable and flexible array of penetrating electrodes for the purposes of stimulating and measuring the electrical activity of excitable tissue, (ii) the characterization of the electrical, mechanical, and biocompatibility properties of this electrode array, (iii) the measurement of regional electrical activity of muscle via the electrode array, (iv) the study of the effect of spatially distributed stimulation of muscle on the fatigue and ripple of muscle contractions, and (v) the assessment of the extent to which the stretch response of electrically stimulated muscle behaves in a physiological manner.
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Lu, Yunxiang. "Study of electrochemical performance of strontium doped lanthanum cobalt oxides using electrochemical impedance spectroscopy and microelectrode array cell design /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/9818.
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Cotterill, Ellese. "Statistical analysis of neuronal data : development of quantitative frameworks and application to microelectrode array analysis and cell type classification." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/267741.
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With increasing amounts of data being collected in various fields of neuroscience, there is a growing need for robust techniques for the analysis of this information. This thesis focuses on the evaluation and development of quantitative frameworks for the analysis and classification of neuronal data from a variety of contexts. Firstly, I investigate methods for analysing spontaneous neuronal network activity recorded on microelectrode arrays (MEAs). I perform an unbiased evaluation of the existing techniques for detecting ‘bursts’ of neuronal activity in these types of recordings, and provide recommendations for the robust analysis of bursting activity in a range of contexts using both existing and adapted burst detection methods. These techniques are then used to analyse bursting activity in novel recordings of human induced pluripotent stem cell-derived neuronal networks. Results from this review of burst analysis methods are then used to inform the development of a framework for characterising the activity of neuronal networks recorded on MEAs, using properties of bursting as well as other common features of spontaneous activity. Using this framework, I examine the ontogeny of spontaneous network activity in in vitro neuronal networks from various brain regions, recorded on both single and multi-well MEAs. I also develop a framework for classifying these recordings according to their network type, based on quantitative features of their activity patterns. Next, I take a multi-view approach to classifying neuronal cell types using both the morphological and electrophysiological features of cells. I show that a number of multi-view clustering algorithms can more reliably differentiate between neuronal cell types in two existing data sets, compared to single-view clustering techniques applied to either the morphological or electrophysiological ‘view’ of the data, or a concatenation of the two views. To close, I examine the properties of the cell types identified by these methods.
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Parviz, Maryam. "Evaluation of Zinc Toxicity Using Neuronal Networks on Microelectrode Arrays: Response Quantification and Entry Pathway Analysis." Thesis, University of North Texas, 2007. https://digital.library.unt.edu/ark:/67531/metadc3928/.
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Murine neuronal networks, derived from embryonic frontal cortex (FC) tissue grown on microelectrode arrays, were used to investigate zinc toxicity at concentrations ranging from 20 to 2000 mM total zinc acetate added to the culture medium. Continual multi-channel recording of spontaneous action potential generation allowed a quantitative analysis of the temporal evolution of network spike activity generation at specific zinc acetate concentrations. Cultures responded with immediate concentration-dependent excitation lasting from 5 to 50 min, consisting of increased spiking and enhanced, coordinated bursting. This was followed by irreversible activity decay. The time to 50% and 90% activity loss was concentration dependent, highly reproducible, and formed linear functions in log-log plots. Network activity loss generally preceded morphological changes. 20% cell swelling was correlated with 50% activity loss. Cultures pretreated with the GABAA receptor antagonists bicuculline (40 mM) and picrotoxin (1 mM) lacked the initial excitation phase. This suggests that zinc-induced excitation may be mediated by interfering with GABA inhibition. Partial network protection was achieved by stopping spontaneous activity with either tetrodotoxin (200 nM) or lidocaine (250 mM). However, recovery was not complete and slow deterioration of network activity continued over 6 hrs. Removal of zinc by early medium changes showed irreversible, catastrophic network failure to develop in a concentration-dependent time window between 50% and 90% activity loss. Investigation of entry routes suggested the L-type but not N-type calcium channels to be the main entry pathway for zinc. Data are presented implicating the chloride channel to be an additional entry route.
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Wu, Calvin. "In Vitro Cortical Networks for Disease Modeling and Drug Evaluation." Thesis, University of North Texas, 2013. https://digital.library.unt.edu/ark:/67531/metadc407860/.
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In translational research, disease models in preclinical studies are used as media for discovery of drugs or novel therapeutics. Development of in vitro models for various neurological diseases that enable efficient pharmacological or toxicological screening has been ongoing but challenging. Recognizing the potential benefit of in vitro disease models, dysfunctions in the cortical neuronal networks were induced to mimic the functional pathology of neurological symptoms using microelectrode arrays. Two different disease states – tinnitusand excitotoxicity – were investigated and discussed. In this model, pentylenetetrazol-induced increase in spontaneous firing rate and synchrony in the auditory cortical networks was used as correlate of tinnitus. Potential tinnitus treatment drugs from several different classes – including the novel class of potassium channel openers – were screened and quantified. The potentialtherapeutic values of these drugs were also discussed as the basis for drug repurposing. Functional excitotoxicity was induced by cisplatin (a cancer drug that causes neurological sideeffects) and glutamate (the major excitatory neurotransmitter). As proof-of-principle that the model may contribute to expediting the development of therapeutics, cisplatin excitotoxicity wasprevented by the antioxidant D-methionine, while glutamate excitotoxicity was prevented by ceftriaxone (a modulator of a glutamate reuptake transporter). In the latter part of the study, with results linking two of the screened drugs L-carnitine and D-methionine to GABAA receptor activation, it was demonstrated that this model not only served as an efficient drug-screening platform, but can be utilized to functionally investigate the underlying mechanism of drugs. Inaddition, several practical or conceptual directions for future studies to improve on this in vitro disease model are suggested.
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Brady, Charlotte Louise. "Development and characterisation of microelectrodes for extreme environments." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/7852.
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Microelectrodes have been found to be a valuable tool in a variety of analytical studies. Their advantages over macro-sized electrodes are well known, including their enhanced mass transport properties (due to their ubiquitous hemispherical diffusion) which lead to steady state responses without external convection. They also exhibit high signal-to-noise ratios (greater sensitivities), furthering their analytical application. Microelectrode arrays are analytical devices with multiple electrodes. There are suitable for practical sensing with all the benefits of microelectrodes but with greater currents, leading to greater ease of measurement. To produce a reliable electroanalytical device the microelectrode response must be reproducible, a fundamental property based on the quality control of their production. Square microelectrode and array fabrication techniques have been developed for this purpose. This research discusses the fabrication and development of closely spaced arrays of square microelectrodes. Simulated and measured responses are compared and used to characterize electrode and array responses by cyclic voltammetry, electrical impedance spectroscopy and current-time transients. Measurements on variably spaced arrays allow insight into overlap of hemispherical diffusion from individual electrodes and the subsequent effect including peak current output on the array device. By studying these devices key insights into the mass transport properties of single square microelectrodes and microelectrode arrays were gained. This study also prepares and develops microelectrodes from materials appropriate for use in the extreme environments of molten salts and concentrated nitric acid solutions. These robust electrodes were developed for use in hydro- and pyro-chemical techniques for nuclear fuel reprocessing. These results demonstrate the practical uses for microelectrode systems across a wide range of chemical systems and in extreme conditions.
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Kuykendal, Michelle Lea. "Closed-loop optimization of extracellular electrical stimulation for targeted neuronal activation." Diss., Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/52303.
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We have developed a high-throughput system of closed-loop electrical stimulation and optical recording that facilitates the rapid characterization of extracellular stimulus-evoked neural activity. The ability to selectively stimulate a neuron is a defining characteristic of next-generation neural prostheses. Greater stimulus control and differential activation of specific neuronal populations allows for prostheses that better mimic their biological counterparts.
In our system, we deliver square current pulses using a microelectrode array; automated real-time image processing of high-speed digital video identifies the neuronal response; and a feedback controller alters the applied stimulus to achieve a targeted response. The system controller performs directed searches within the strength-duration (SD) stimulus parameter space to build probabilistic neuronal activation curves. An important feature of this closed-loop system is a reduction in the number of stimuli needed to derive the activation curves when compared to the more commonly used open-loop system: this allows the closed-loop system to spend more time probing stimulus regions of interest in the multi-parameter waveform space, facilitating high resolution analysis.
The stimulus-evoked activation data were well-fit to a sigmoid model in both the stimulus strength (current) and duration (pulse width) slices through the waveform space. The 2-D analysis produced a set of probability isoclines corresponding to each neuron-electrode pairing, which were fit to the SD threshold model described by Lapique (1907). We show that stimulus selectivity within a given neuron pair is possible in the one-parameter search space by using multiple stimulation electrodes. Additionally, by applying simultaneous stimuli to adjacent electrodes, the interaction between stimuli alters the neuronal activation threshold. The interaction between simultaneous multi-electrode multi-parameter stimulus waveforms creates an opportunity for increased stimulus selectivity within a population.
We demonstrated that closed-loop imaging and micro-stimulation technology enable the study of neuronal excitation across a large parameter space, which is requisite for controlling neuronal activation in next generation clinical solutions.
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Ghasemi, Tahrir Farzaneh. "DYSREGULATION of PROTEIN QUALITY CONTROL IMPAIRS FUNCTION of PRIMARY CARDIOMYOCYTES." Diss., Temple University Libraries, 2018. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/525002.
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BioengineeringPh.D.
Mitochondria provide the main energy required for cardiac excitation-contraction coupling via aerobic oxidative phosphorylation (OXPHOS) process. Accumulation of reactive oxygen species (ROS), by-products of mitochondrial respiration, within dysfunctional mitochondria results in the activation of cardiac cell death pathways and has been associated with heart failure development. Therefore, maintaining mitochondrial homeostasis as a balance between mitochondrial biogenesis and degradation is of great importance toward cardiac proper functioning. In addition to the importance of mitochondrial energy supply, gap junctions, intercellular channels which connect plasma membrane of adjacent cardiomyocytes, by propagating action potential throughout the myocardium maintain cardiac synchronous beating and rhythm. Gap junctions have a rapid turnover and impair of gap junction quality control impacts cell-to-cell communication; resulting in electrical conduction abnormalities and arrhythmogenesis. Therefore, understanding the underlying mechanism the quality control of mitochondria and gap junctions profoundly contributes toward understating the genesis of cardiomyopathy. Furthermore, cardiovascular problems in HIV (Human immunodeficiency virus) positive patients whose viral load is controlled via antiretroviral therapy remains a problem while the underlying mechanism remains elusive. The current study has used an in vitro model of primary neonatal rat ventricular cardiomyocytes (NRVCs) to discover the molecular mechanisms of mitochondrial as well as gap junction quality control under normal and stress conditions. Furthermore, electrical activities of the primary cardiomyocytes were recorded using microelectrode array (MEA) system and important electrophysiological components such as impulse propagation pattern and conduction velocity were extracted from the complex signal recordings. Overall, we have pursued four main aims; Aim 1. Dysregulation of mitochondrial quality control machinery leads to cardiac death; Aim 2. HIV-1 Tat (transcriptional transactivator) dysregulates cardiac homeostasis via mitochondrial pathway; Aim 3. Impairment of protein quality control impacts the quality of gap junction; Aim 4. Inhibition of gap junction quality dysregulates electrical signal propagation within the culture.
Temple University--Theses
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Tolstosheeva, Elena [Verfasser], Walter [Akademischer Betreuer] Lang, Walter [Gutachter] Lang, and Andreas [Gutachter] Kreiter. "A Flex-Rigid, Multi-Channel ECoG Microelectrode Array : Reliable Electrical Contact & Long-Term Stability in Saline / Elena Tolstosheeva ; Gutachter: Walter Lang, Andreas Kreiter ; Betreuer: Walter Lang." Bremen : Staats- und Universitätsbibliothek Bremen, 2017. http://d-nb.info/1160670609/34.
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Dian, Emese Emöke. "Application of Cultured Neuronal Networks for Use as Biological Sensors in Water Toxicology and Lipid Signaling." Thesis, University of North Texas, 2004. https://digital.library.unt.edu/ark:/67531/metadc5557/.
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This dissertation research explored the capabilities of neuronal networks grown on substrate integrated microelectrode arrays in vitro to be applied to toxicological research and lipid signaling. Chapter 1 details the effects of chlorine on neuronal network spontaneous electrical activity and pharmacological sensitivity. This study demonstrates that neuronal networks can maintain baseline spontaneous activity, and respond normally to pharmacological manipulations in the present of three times the chlorine present in drinking water. The findings suggest that neuronal networks may be used as biological sensors to monitor the quality of water and the presence of novel toxicants that cannot be detected by conventional sensors. Chapter 2 details the neuromodulatory effects of N-acylethanolamides (NAEs) on the spontaneous electrical activity of neuronal networks. NAEs are a group of lipids that can mimic the effects of marijuana and can be derived from a variety of plant sources including soy lecithin. The most prominent NAEs in soy lecithin, palmitoylethanolamide (PEA) and linoleoylethanolamide (LEA), were tested individually and were found to significantly inhibit neuronal spiking and bursting activity. These effects were potentiated by a mixture of NAEs as found in a HPLC enriched fraction from soy lecithin. Cannabinoid receptor-1 (CB1-R) antagonists and other cannabinoid pathway modulators indicated that the CB1-R was not directly involved in the effects of NAEs, but that enzymatic degradation and cellular uptake were more likely targets. The results demonstrate that neuronal networks may also be a viable platform for the elucidation of biochemical pathways and drug mechanisms of action.
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Okeyo, George Odhiambo. "Functional studies of purified recombinant BK[subscript CA ]channels and the mechanosensitive channel of high conductance (MscL) reconstituted in bilayer lipid membranes tethered to a microelectrode array device." [Gainesville, Fla.] : University of Florida, 2009. http://purl.fcla.edu/fcla/etd/UFE0041236.
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Rajaraman, Swaminathan. "Micromachined three-dimensional electrode arrays for in-vitro and in-vivo electrogenic cellular networks." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/28129.
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Thesis (M. S.)--Electrical and Computer Engineering, Georgia Institute of Technology, 2009.Committee Chair: Mark G. Allen; Committee Member: Elliot L. Chaikof; Committee Member: Ionnis (John) Papapolymerou; Committee Member: Maysam Ghovanloo; Committee Member: Oliver Brand.
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Apaydin, Elif. "Microfabrication Techniques for Printing on PDMS Elastomers for Antenna and Biomedical Applications." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1253138931.
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O'Brien, David Patrick. "Micromachined microelectrode arrays for stimulation of neural tissue." Diss., Georgia Institute of Technology, 2000. http://hdl.handle.net/1853/14993.
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Psalti, Ioanna S. M. "Microelectrodes : single and arrays in electron transfer." Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302826.
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Gunning, Deborah. "High density microelectrode arrays for in vitro retinal studies." Thesis, University of Glasgow, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.443419.
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Moutaux, Eve. "Régulation du transport axonal par l'activité neuronale : Implication pour le développement des réseaux neuronaux Neuronal activity recruits an axon-resident pool of secretory vesicles to regulate axon branching Reconstituting Corticostriatal Network on-a-Chip Reveals the Contribution of the Presynaptic Compartment to Huntington’s Disease Neuronal network maturation differently affects secretory vesicles and mitochondria transport in axons ALG-2 interacting protein-X (Alix) is required for activity-dependent bulk endocytosis at brain synapses An integrated microfluidic/microelectrode array for the study of activity-dependent intracellular dynamics in neuronal networks." Thesis, Université Grenoble Alpes, 2020. https://thares.univ-grenoble-alpes.fr/2020GRALV024.pdf.
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Pendant le développement, les projections axonales à longue distance se ramifient pour se connecter à leurs cibles. L’établissement et le remodelage de ces connexions est notamment régulé par l’activité neuronale. L’adaptation de la morphologie de l’axone nécessite alors des quantités importantes de matériel sécrétoire et de facteur trophiques comme le BDNF (brain derived neurotrophic factor). Ce matériel est transporté dans des vésicules le long de l’axone depuis le corps cellulaire où il est synthétisé, vers les sites actifs à l’extrémité de l’axone. Si le relargage de vésicules sécrétoires à la synapse est bien étudié, les mécanismes régulant le transport axonal par l’activité sont encore méconnus.Dans ce travail de thèse, nous avons dans un premier temps développé des outils permettant d’étudier les dynamiques intracellulaires dans des réseaux neuronaux. Nous avons ainsi développé une chambre microfluidique permettant de reconstruire in vitro des réseaux neuronaux physiologiques et compatibles avec de la vidéomicroscopie à haute résolution. Nous avons caractérisé l’établissement et la maturation du réseau et validé l’intérêt de ce dispositif microfluidique dans le contexte de la maladie de Huntington. Nous avons ensuite étudié l’évolution des dynamiques intracellulaires avec la maturation du réseau. Nous avons notamment observé une augmentation du transport axonal de vésicules sécrétoires en fonction de l'état de maturation du réseau neuronal. Ces premières observations ont renforcé l’hypothèse d’une régulation directe du transport axonal de vésicules sécrétoires par l’activité neuronale au cours du développement du réseau.Nous avons ainsi fait évoluer la plateforme microfluidique par l’ajout d’un réseau d’électrodes (MEA) qui permet d'étudier les dynamiques intracellulaires tout en contrôlant l’activité neuronale. A l’aide de ce système, nous avons identifié un groupe de vésicules sécrétoires ancré le long de l’axone et recruté en réponse à une haute activité neuronale en direction des sites présynaptiques actifs. Nous avons alors identifié les acteurs impliqués dans ce mécanisme dépendant de l’activité. Nous avons montré que la myosine Va permettait l’attachement des vésicules le long de l’axone dans des structures d’actine dynamique. L’activité neuronale induit une augmentation de calcium le long de l’axone, via l’activation des canaux calciques dépendant du voltage, qui régule la myosine Va et entraine le recrutement des vésicules stockées dans l’axone sur les microtubules. Une fois les acteurs identifiés, nous avons pu mettre en évidence le rôle de ce mécanisme dépendant de l’activité dans la formation de branches axonales pendant le développement. Enfin, nous avons confirmé l’existence de ce groupe de vésicules dépendant de l’activité et résidant dans l’axone in vivo grâce à la mise au point d'un système d’étude du transport axonal sur tranches aigües de cerveau en microscopie biphotonique.L’ensemble de ce travail propose de nouveaux outils in vitro et in vivo pour comprendre les régulations des dynamiques intracellulaires dans des réseaux neuronaux physiologiques. Grâce à ces outils, nous avons identifié un mécanisme de régulation local qui permet l'adressage rapide de facteurs trophiques vers les branches en développement en réponse à l’activité neuronaleDuring postnatal development, long-distance axonal projections form branches to connect with their targets. Establishment and remodeling of these projections are tightly regulated by neuronal activity and require a large amount of secretory material and trophic factors, such as brain derived neurotrophic factor (BDNF). Axonal transport is responsible for addressing trophic factors packed into vesicles to high demand sites where mechanisms of secretion are well-known. However, mechanisms controlling the preferential targeting of axonal vesicles to active sites in response to neuronal activity are unknown.In this work, we first developed tools to study intracellular dynamics in neuronal networks. We thus developed a microfluidic chamber to reconstruct physiologically-relevant networks in vitro which is compatible with high resolution videomicroscopy. We characterized the formation and maturation of reconstructed networks and we validated the relevance of the microfluidic platform in the context of Huntington’s disease. We then studied the evolution of intracellular dynamics with the maturation of reconstructed neuronal networks in microfluidic chambers. We observed an increase of anterograde axonal transport of secretory vesicles during maturation. These first results lead us to think that neuronal activity could regulate axonal transport of secretory vesicles over maturation of the network.Therefore, we improved the in vitro microfluidic system with a designed microelectrode array (MEA) substrate allowing us to record intracellular dynamics while controlling neuronal activity. Using this system, we identified an axon-resident reserve pool of secretory vesicles recruited upon neuronal activity to rapidly distribute secretory materials to presynaptic sites. We identified the activity-dependent mechanism of recruitment of this axonal pool of vesicles along the axon shaft. We showed that Myosin Va ensures the tethering of vesicles in the axon shaft in axonal actin structures. Specifically, neuronal activity induces a calcium increase after activation of Voltage Gated Calcium Channels along the axon, which regulates Myosin Va and triggers the recruitment of tethered vesicles on microtubules. We then showed the involvement of this activity-dependent pool for axon branches formation during axon development. By developing 2-photon live microscopy of axonal transport in acute slices, we finally confirmed that a pool of axon-resident static vesicles is recruited by neuronal activity in vivo with a similar kinetic.Altogether, this work provides new in vitro and in vivo tools to study intracellular dynamics in physiological networks. Using these tools, we identified the existence of a local mechanism of axonal transport regulation along the axon shaft, allowing rapid supply of trophic factors to developing branches
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Guo, Liang. "High-density stretchable microelectrode arrays: an integrated technology platform for neural and muscular surface interfacing." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/39513.
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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 microns in diameter; (2) we have patterned high-resolution (feature as small as 10 microns), high-density (pitch as small as 20 microns) 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.
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Zim, Bret E. "Improved Fabrication and Quality Control of Substrate Integrated Microelectrode Arrays." Thesis, University of North Texas, 2000. https://digital.library.unt.edu/ark:/67531/metadc2484/.
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Spontaneously active monolayer neuronal networks cultured on photoetched multimicroelectrode plates (MMEPs) offer great potential for use in studying neuronal networks. However, there are many problems associated with frequent, long-term use of MMEPs. The major problems include (1) polysiloxane insulation deterioration and breakdown, (2) and loss of gold at the gold electroplated indium-tin oxide (ITO) electrodes. The objective of this investigation was to correct these major problems. Quality control measures were employed to monitor MMEP fabrication variables. The phenotypes of polysiloxane degradation were identified and classified. Factors that were found to contribute most to insulation deterioration were (1) moisture contamination during MMEP insulation, (2) loss of the quartz barrier layer from excessive exposure to basic solutions, and (3) repetitive use in culture. As a result, the insulation equipment and methods were modified to control moisture-dependent insulation deterioration, and the KOH reprocessing solution was replaced with tetramethylguanidine to prevent damage to the quartz. The problems associated with gold electroplating were solved via the addition of a pulsed-DC application of gold in a new citrate buffered electroplating solution.
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Long, Brian Russell. "Transport of polymers and particles in microfabricated array devices /." Connect to title online (Scholars' Bank) Connect to title online (ProQuest), 2008. http://hdl.handle.net/1794/8289.
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Thesis (Ph. D.)--University of Oregon, 2008.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 122-127). Also available online in Scholars' Bank; and in ProQuest, free to University of Oregon users.
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Tang, Rongyu. "Listening to neurons : development and understanding of microelectrode arrays (MEA's) systems." Thesis, University of Glasgow, 2009. http://theses.gla.ac.uk/778/.
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This thesis is about the development of microelectrodes array system (MEAs), the simulation of the neuron and the recording to the living neural network. We cultured the nerve cells of rat inside a container called 'neural bathtub' and guided them to form predetermined network (Jude pattern) with topographical features or protein traces. In order to record the electrical activity of these nerve cells, two types of MEA systems (FlexMEAs and pMEAs) were designed and built. These extracellular MEA systems were aimed to form one-electrode-to-one-neuron connection with neural network. To assist the design, many models were built, e. g. the impedance model of the microelectrode/electrolyte interface, the oxygen model inside the 'neural bathtub'. During this project many difficulties were encountered especially at the coupling of MEA to neurons. To explore these questions more models and simulations were included into this thesis. The excitable membrane of neuron and the interface of neuron to microelectrode are modelled and investigated. These simulations help to explain many questions, e.g. how to form a good coupling of neuron/electrode, how the waveform of extracellular spikes changes and how much power is dissipated when neuron generates an action potential. The first chapter introduces this project, the history of MEA and some biology about neuron. The fabrication processes of devices (the MEAs, the 'bathtub', the mould of Jude pattern and the preamplifier) are described in the second chapter. Chapter 3 gives the detail of the designs of these devices and how they were evolved and optimised. Chapter 4 is about the impedance model of the microelectrode, the measurements of the impedance and the data fitting to obtain the parameters of the model. Chapter 5 models the oxygen concentration inside the 'neural bathtub'. The simulation tells whether the diffusion provides enough oxygen to sustain the nerve cells. It helped us to modify the design of 'neural bathtub'. Chapter 6 introduces the basic principle of different microelectrode system from a circuit perspective. The importance of the seal resistance to the coupling of neuron/electrode is investigated using a circuit model. The noise caused by the preamplifier itself is estimated also. Chapter 6 also introduces a model based on the classical model by Hodgkin and Huxley (1952). The differences between the waveforms of the extracellular potential are explored with the help of the model in this chapter. Chapter 7 represents the signal recorded from different cells with different setups. The signal is analysed preliminarily.
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Pirlo, Russell Kirk. "Creation of defined single cell resolution neuronal circuits on microelectrode arrays." Connect to this title online, 2009. http://etd.lib.clemson.edu/documents/1252937942/.
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Kitzmiller, Joseph Paul. "Design, engineering,and evaluation of a novel microgrid electrode array to monitor the electrical activity on the surface of the cerebral cortex." Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1084824069.
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Thesis (Ph. D.)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains xiv, 82 p.; also includes graphics. Includes bibliographical references (p. 80-82). Available online via OhioLINK's ETD Center
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Santa, Maria Cara L. Gross Guenter W. "Optimization of cell culture procedures for growing neural networks on microelectrode arrays." [Denton, Tex.] : University of North Texas, 2007. http://digital.library.unt.edu/permalink/meta-dc-5126.
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