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Proposed research object aims to develop and implement the novel imaging technique to delineate tissue boundaries based on electrical impedance of tissues.

Multi electrode array (MEA) systems have evolved from custom-made experimental tools, exploited for neural research, into commercially available systems that are used throughout non-invasive electrophysiological study. MEA systems are used in conjunction with cells and tissues from a number of differing organisms (e.g. mice, monkeys, chickens, plants). The development of MEA systems has been incremental over the past 30 years due to constantly changing specific bioscientific requirements in research. As the application of MEA systems continues to diversify contemporary commercial systems are requiring increased levels of sophistication and greater throughput capabilities.

The interactions between neighboring cells and between cells and their attached substrate have long been studied in tissue culture. These in vitro studies may provide information regarding cell behavior in vivo including cell movement, cell proliferation, tissue development and wound healing. Transcellular resistance (or impedance) measurements, using various dc or ac techniques have been used to study the barrier function of epithelial and endothelial cell layers. With an appropriate equivalent circuit used for data analysis, junctional resistance between cells and other cellular properties, including cell membrane capacitance, can be determined. However, these techniques have seldom been applied to fibroblastic cell layers because the transcellular resistance is so small that it is difficult to measure it accurately. This research is based on detecting the invasive activities of metastatic cells in vitro using electric cell-impedance sensing (ECIS). The metastatic cells where added over the established endothelial cells and were observed to attach and invade the cell layer. Human umbilical vein endothelial cells (HUVECs) were first grown and then loaded on eight well gold electrodes. The impedance of these electrodes was followed after the suspension of different sublines of cancer cells (SKOV3, OVCA429). For highly metastatic sublines, within an hour after being challenged, the impedance of confluent HUVECs layer was substantially reduced. In addition the conditioned cancer media and heat-killed cancer cells was also suspended which had no substantial effect on the impedance. This result suggests that ECIS based assay might be used with primary human cultures to establish the metastatic abilities of cells.

The objective of this thesis is to provide additional insight into the electrode array-nerve fibre interface that exists in the implanted cochlea and to facilitate investigation of new electrode arrays in interaction with the cochlea and auditory nerve fibres. The focus is on potential distributions and excitation profiles generated by different electrode array types and factors that could have an influence on these distributions and profiles. Research contributions made by the thesis are the creation of a detailed 3-D model of the implanted cochlea that accurately predicts measurable effects in cochlear implant wearers and facilitates effortless simulation of existing and new electrode array variations; the establishment of the important anatomical structures required in a 3-D representation of the implanted cochlea; establishment of evidence that array location is the primary parameter that controls spread of excitation; definition of the critical focussing intensity of intracochlear electrode pairs; confirmation thatmonopolar stimulation could deliver focussed stimulation to approximately the same degree than that delivered by widely spaced electrode configurations and that the use of monopolar configurations over bipolar configurations are therefore advantageous under certain conditions; explanation of the effect that encapsulation tissue around cochlear implant electrodes could have on neural excitation profiles; extension of the information available on the focussing ability of multipolar intracochlear electrode configurations; and establishment of evidence that a higher lateral electrode density could facilitate better focussing of excitation, continuous shaping of excitation profiles and postoperative customization of electrode arrays for individual implant wearers. / Dissertation (PhD(Electronic Engineering))--University of Pretoria, 2001. / Electrical, Electronic and Computer Engineering / Unrestricted

Thesis advisor: Michael J. Naughton / Nanoscale biosensing devices improve and enable detection mechanisms by taking advantage of properties inherent to nanoscale structures. This thesis primarily describes the development, characterization and application of two such nanoscale structures. Namely, these two biosensing devices discussed herein are (1) an extended-core coaxial nanogap electrode array, the ‘ECC’ and (2) a plasmonic resonance optical filter array, the ‘plasmonic halo’. For the former project, I discuss the materials and processing considerations that were involved in the making of the ECC device, including the nanoscale fabrication, experimental apparatuses, and the chemical and biological materials involved. I summarize the ECC sensitivity that was superior to those of conventional detection methods and proof-of-concept bio-functionalization of the sensing device. For the latter project, I discuss the path of designing a biosensing device based on the plasmonic properties observed in the plasmonic halo, including the plasmonic structures, materials, fabrication, experimental equipment, and the biological materials and protocols. / Thesis (PhD) — Boston College, 2019. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Physics.

The objective of this research was to evaluate the technical and economic feasibility of employing an electric field to enhance the dewatering performance of two types of biological sludge by a pilot-scale plate and frame filter press. In this work a biological industrial sludge and biological municipal sludge were collected and tested, respectively. Through the jar testing, it was found that a low molecular weight cationic polymer or medium molecular weight cationic polymer with a dose of 0.008 wt% would yield a satisfactory flocculation for the biological industrial sludge, whereas an iron-based coagulant with a dose of 0.08 wt% would meet the conditioning need of the biological municipal sludge. To find out the optimal dewatering conditions for the concerned sludges, experimental designs based on the Taguchi method were adopted. More specifically, L8(27) and L18(21¡Ñ37) orthogonal arrays were selected for the biological industrial sludge and biological municipal sludge, respectively. Among others, applied mechanical pressure and time, electrode array, and electrodewatering time were operating parameters of concern. Test results showed that a 10-15% increase of dewatering efficiency for both sludges was obtained for the parallel circuit and parallel series circuit. However, the filtrate quality deteriorated, particularly in pH, turbidity, and chemical oxygen demand. In addition, due to ohmic heating the temperature of filtrate might raise to 80 ¢Jor even higher depending on the operating conditions employed. Thus, the filtrate should be recirculated back to the wastewater treatment system for proper treatment. To find out the significant controlling factors and optimal operating conditions for electrodewatering in a more scientific manner, the final sludge cake moisture and energy consumption for each test was subjected to formal analysis and analysis of variance. For biological industrial sludge, the flocculant type and applied filtration pressure were found to be the most significant controlling factors for the final sludge cake moisture, whereas the applied electric field strength for the power consumption. In the case of biological municipal sludge, however, the electrode array was the most significant controlling factor for both final sludge cake moisture and power consumption. At last, the optimal operating conditions theoretically obtained for electrodewatering were subjected to the respective verification tests for both biological industrial sludge and biological municipal sludge. Test results showed that a final sludge cake moisture of 67.1¡Ó3.9% and energy consumption of 72.6 kWh/ton dry solids were obtained for the former sludge, whereas 68.1¡Ó3.4% and 18.6 kWh/ton dry solids for the latter sludge. These results validated the predictions made by the Taguchi method. Therefore, it may conclude that electrodewatering is technically and economically feasible for treating both biological industrial sludge and biological municipal through the electrokinetics-assisted filter press system employed in this work.

The retina contains neural circuits that carry out computations as complex as object motion sensing, pattern recognition, and position anticipation. Models of some of these circuits have been recently discovered. A remarkable outcome of these efforts is that all such models can be constructed out of a limited set of components such as linear filters, instantaneous nonlinearities, and feedback loops. The present study explores the consequences of assuming that these components can be used to construct models for all retinal circuits. I recorded extracellularly from several retinal ganglion cells while stimulating the photoreceptors with a movie rich in temporal and spatial frequencies. Then I wrote a computer program to fit their responses by searching through large spaces of anatomically reasonable models built from a small set of circuit components. The program considers the input and output of the retinal circuit and learns its behavior without over-fitting, as verified by running the final model against previously unseen data. In other words, the program learns how to imitate the behavior of a live neural circuit and predicts its responses to new stimuli. This technique resulted in new models of retinal circuits that outperform all existing ones when run on complex spatially structured stimuli. The fitted models demonstrate, for example, that for most cells the center--surround structure is achieved in two stages, and that for some cells feedback is more accurately described by two feedback loops rather than one. Moreover, the models are able to make predictions about the behavior of cells buried deep within the retina, and such predictions were verified by independent sharp-electrode recordings. I will present these results, together with a brief collection of ideas and methods for furthering these modeling efforts in the future. / Physics

D-Serine is regarded as an obligatory co-agonist required for the activation of NMDA-type glutamate receptors (NMDARs). In the retina D-serine and a second NMDAR coagonist, glycine, are present at similar concentration and the cells that produce and release them are in close apposition. This arrangement allows for an abundant supply of coagonists and under certain conditions the NMDAR coagonist binding site could be saturated. There is also evidence suggesting that D-serine can act in an inhibitory manner at AMPA/kainate-type glutamate receptors (GluRs). Glutamate receptor activation can lead to direct and indirect elevation of intracellular calcium (Ca2+) concentration ([Ca2+]i). Therefore, in this thesis, I predominantly used Ca2+ imaging techniques to study the effect of D-serine on GluR activation in the mammalian retina. I first describe a novel method I developed to load retinal cells with Ca2+ indicator dye using electroporation and show that retinas remain viable and responsive following electroporation. This technique was used to explore the excitatory role of D-serine at NMDARs and its potential inhibition of AMPA/kainate receptors using cultured retinal ganglion cells (RGCs) and isolated retina preparations. Using cultured RGCs I demonstrated that D-serine and glycine enhance NMDAR-mediated Ca2+ responses in a concentration-dependent manner and are equally effective as coagonists. In isolated retinas I showed that D-serine application enhanced NMDA-induced responses consistent with sub-saturating endogenous coagonist concentration. Degradation of endogenous D-serine reduced NMDAR-mediated Ca2+ responses supporting the contribution of this coagonist to NMDAR activation in the retina. Using imaging and two different electrophysiological approaches, I found that D-serine reduced AMPA/kainate receptor-mediated responses in cultured RGCs and isolated retinas at concentrations that are saturating at NMDARs. Antagonist experiments suggest that the majority of inhibition is due to D-serine acting on AMPA receptor activity. Degradation of endogenous D-serine enhanced AMPA/kainate-induced responses of some cells in isolated retina suggesting that, under these conditions, D-serine concentration may be sufficient to inhibit AMPA receptor activity. Overall, the work in this thesis illustrates the utility of electroporation as a method to load Ca2+-sensitive fluorescent dyes into retinal cells and highlights the potential role for D-serine as a modulator of ionotropic GluRs in the CNS.

Die vorliegende Arbeit befasst sich mit der Anwendbarkeit von transparenter Elektronik basierend auf oxidischen Halbleitern in Multielektrodenarrays zur Messung von neuronalen Signalen. Im ersten experimentellen Kapitel werden auf Zinkoxid basierende Bauelemente untersucht. Verschiedene Varianten von Feldeffekttransistoren (FETs) werden charakterisiert und ihre Eignung zur Detektion von Zellsignalen überprüft. Die Anwendbarkeit physikalischer Modelle zur Beschreibung von ZnO-basierten Metal-Halbleiter-FETs (MESFETs) wird behandelt. Weiterhin wird die Eignung von einfachen Inverterschaltungen zur Spannungsverstärkung diskutiert. Das zweite Kapitel thematisiert Rauschmessungen an unterschiedlichen ZnO-basierten Proben, darunter Dünnfilme, Mikronadeln, MESFETs und Inverter. Darauf aufbauend wird die Auswirkung des gemessenen Stromrauschens auf die Sensitivität der Bauelemente nachvollzogen und theoretisch modelliert. Im dritten Kapitel wird das Verhalten der Bauelemente im Kontakt mit Elektolyt beschrieben. Die Signalübertragung von Spannungsänderungen im Elektrolyt auf die Chipelektronik wird mit verschiedenen Messmethoden charakterisiert. Dabei kommt teilweise ein selbstgebauter Vorverstärker zum Einsatz, dessen Aufbau ebenfalls beschrieben wird. Die Stabilität der verwendeten Materialien in physiologischen Salzlösungen und ihre Biokompatibilität wird überprüft. Darüber hinaus werden FETs mit Elektrolytgate und Zinkzinnoxid-Kanal vorgestellt.