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Bioimpedance is the term given to the complex impedance value that is characteristic of the resistance that biological cells offer to the flow of electric current. The objective of this study is to analyze the differences in the bioimpedance of highly metastatic MDA-MB-231 and normal MCF 10A breast epithelial cells and use this information to detect a very small number of breast cancer cells present in a background of normal breast cells and other cells that are typically present in a human biopsy sample.To accomplish this, a bioimpedance sensor with flat gold microelectrodes on a silicon substrate was designed and fabricated. Suberoylanilide hydroxamic acid (SAHA), an FDA-approved anti-cancer agent was used to improve the sensitivity of the bioimpedance sensor towards cancer cells by selectively modifying their cytoarchitecture. / Master of Science

This research utilizes Electrical Impedance Spectroscopy, a technique classically used for electrochemical analysis and material characterization, as the basis for a non-destructive, label-free assay platform for three dimensional (3D) cellular spheroids. In this work, a linear array of microelectrodes is optimized to rapidly respond to changes located within a 3D multicellular model. In addition, this technique is coupled with an on chip micro-pH sensor for monitoring the environment around the cells. Finally, the responses of both impedance and pH are correlated with physical changes within the cellular model. The impedance analysis system realized through this work provides a foundation for the development of high-throughput drug screening systems that utilize multiple parallel sensing modalities including pH and impedance sensing in order to quickly assess the efficacy of specific drug candidates. The slow development of new drugs is mainly attributed to poor predictability of current chemosensitivity and resistivity assays, as well as genetic differences between the animal models used for tests and humans. In addition, monolayer cultures used in early experimentation are fundamentally different from the complex structure of organs in vivo. This requires the study of smaller 3D models (spheroids) that more efficiently replicate the conditions within the body. The main objective of this research was to develop a microfluidic system on a chip that is capable of deducing viability and morphology of 3D tumor spheroids by monitoring both the impedance of the cellular model and the pH of their local environment. This would provide a fast and reliable method for screening pharmaceutical compounds in a high-throughput system.

A large part of the work presented in this thesis describes the development and use of a novel electrochemical detector designed to allow the electrochemical characterisation of compounds in flowing solution by means of cyclic voltammetry. The detector was microprocessor controlled, which provides digital generation of the potential waveform and collection of data for subsequent analysis. Microdisk working electrodes are employed to permit both thermodynamic and kinetically controlled processes to be studied under steady-state conditions in flowing solutions without the distortion or hysteresis normally encountered with larger sized electrodes. The effect of electrode size, potential scan rate, and solution flow rate are studied extensively with the oxidation of ferrocene used as an example of a thermodynamically controlled process and a series of catecholamines as examples of a kinetically controlled process. The performance of the detector was best demonstrated when used as a HPLC post-column detector. The 3-dimensional chromatovoltammograms obtained allow on-line characterisation of each fraction as it elutes from the column. The rest of the work presented in this thesis involves the study of the oxidative degradation pathway of dithranol. The oxidative pathway was shown to involve a complex free radical mechanism, dependent on the presence of both oxygen and, in particular light. The pathway is further complicated by the fact that dithranol may exist in either a keto or enol form, the enol being most susceptible to oxidation. A likely mechanism is proposed from studies performed with cyclic voltammetry and controlled potential electrolysis, then defined by subsequent kinetic studies.

The aim of this master thesis has been to design, and partly manufacture and evaluate, a highly miniaturized, on-chip conductivity-temperature-depth (CTD) sensor system for deepwater analysis also including electrodes for pH and chloride ion concentration measurements. The microtechnology-based sensor system will be a vital instrument onboard the Deeper Access, Deeper Understanding submersible, which will be small enough for deployment through bore holes into the subglacial lakes of Antarctica. Design of the complete 15 x 30 mm chip, including variations of each sensor type (in total 39 sensors), is presented. Salinity (through conductivity), temperature, chloride ion concentration and pH sensors have been manufactured using conventional lithography, evaporation, wet etching and lift off techniques. Simulations of the pressure sensors (not manufactured) show how the set of four bossed membranes with integrated strain gauges combine to cover, yet withstand, pressures of 1-100 atm. Salinity is measured conductively with gold electrodes. The temperature sensor is a platinum thermoresistor. Chloride ion concentration and pH are measured potentiometrically with ion-selective microelectrodes of silver/silver chloride and iridium oxide, respectively. Tests of the conductivity sensor gave good results also on sea water samples of known salinity. The temperature sensor showed good linearity to a reference sensor in the tested range of 5-35 C. Issues with evaporation and lift off are discussed, and a process identification document is attached. / DADU

This thesis focuses on in-situ studies at the solid-liquid interface by combining scanning electrochemical microscopy (SECM) with gold and platinum mercury amalgam microelectrodes. It is shown that stripping voltammetry experiments at imaging amalgam microelectrodes provide laterally resolved insight on the electrochemistry of biogeochemically relevant processes. SECM provides information on electroactive surface processes with high spatial resolution, and offers the opportunity to study heterogeneous electron-transfer reactions. Thereby, chemical species of interest, such as metal ions, can be electrochemically detected at mercury amalgam electrodes. Platinum and gold mercury amalgam microelectrodes were developed for the detection of biogeochemically relevant analytes such as manganese and iron during SECM imaging experiments at the mineral/water interface establishing the fundamental basis of SECM imaging with amalgam microelectrodes. SECM experiments were performed for the quantitative determination of Mn2+ during the dissolution of microstructured manganese carbonate (rhodochrosite) precipitates at mildly acidic conditions. SECM images along with spatially resolved quantitative data on the Mn2+ concentration were obtained. This measurement concept was then extended to the investigation of the corrosion behavior of diamond-like carbon (DLC) protected zinc selenide (ZnSe) waveguides applied in mid-infrared attenuated total reflectance spectroscopy at strongly oxidizing conditions. The corrosion behavior of DLC coated and uncoated ZnSe crystals was studied obtaining laterally resolved information on the oxidative degradation of ZnSe at defects of the DLC layer utilizing SECM in combination with square wave anodic stripping voltammetry (SWASV) at gold amalgam microelectrodes. Thereby, insight on the corrosion behavior of ZnSe and concentration profiles of Zn2+ at oxidizing conditions was obtained. These results corroborate the utility of SECM imaging with amalgam microelectrodes for addressing relevant analytical questions. Finally, the developed amalgam microelectrodes were applied for SECM studies of iron-reducing proteins separated from Shewanella microbes in native polyacrylamide gels. After calibration of Pt/Hg microelectrodes in bulk solution for the targeted analytes (iron and sulfur species), SECM approach curves recorded above the native gel enabled positioning of the amalgam electrode in close proximity above protein bands with suspected iron-reducing activity. This technique enabled the (semi)quantitative determination of the anaerobic respiratory activity associated with microbial proteins/protein complexes responsible for the reductive dissolution of manganese and iron oxides above microbial protein bands separated in a native gel matrix.

Spontaneous and evoked potentials (EPs) were recorded with cross-cortical microelectrode arrays following partial occlusion of the MCA and ACA in urethane-anaesthetised rats. The control group received no occlusion, while the treatment group was injected with anti-stroke peptide Tat-NR2B9c 5min before ischemia. Spontaneous EEG power significantly decreased in the stroke-only group when compared to controls (p<0.001). A greater loss of EEG power was observed on anterior electrodes closer to the occluded area versus posterior contacts in stroke-only rats (p<0.05). The Tat-NR2B9c+stroke group lost significantly less power when compared to stroke-only animals (p<0.05). EP amplitude in the stroke-only group was significantly reduced following ischemia when compared to control and Tat-NR2B9c+stroke animals (p<0.001). Epileptiform discharges were observed in 8/10 untreated stroke rats and 3/5 stroke rats treated with Tat-NR2B9c. The characteristic features of spontaneous and evoked potentials validate this rat focal stroke model for in vivo testing of pharmacological agents.

Spontaneous and evoked potentials (EPs) were recorded with cross-cortical microelectrode arrays following partial occlusion of the MCA and ACA in urethane-anaesthetised rats. The control group received no occlusion, while the treatment group was injected with anti-stroke peptide Tat-NR2B9c 5min before ischemia. Spontaneous EEG power significantly decreased in the stroke-only group when compared to controls (p<0.001). A greater loss of EEG power was observed on anterior electrodes closer to the occluded area versus posterior contacts in stroke-only rats (p<0.05). The Tat-NR2B9c+stroke group lost significantly less power when compared to stroke-only animals (p<0.05). EP amplitude in the stroke-only group was significantly reduced following ischemia when compared to control and Tat-NR2B9c+stroke animals (p<0.001). Epileptiform discharges were observed in 8/10 untreated stroke rats and 3/5 stroke rats treated with Tat-NR2B9c. The characteristic features of spontaneous and evoked potentials validate this rat focal stroke model for in vivo testing of pharmacological agents.