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.

This doctoral thesis gives background to the field of electrochemical energy storage in supercapacitors. It attempts to place the supercapacitor device in context of available and future technologies for alternative energy systems for transportation. Limitations of cells and electrodes and key challenges in the supercapacitor development are introduced. One objective of the thesis is to investigate and describe ionic transport in active carbon and possible restrictions in nanostructured porous systems with focus on small (micro and meso) pores. Another is to develop a model suitable for investigations of concentration and potential profiles from a single particle perspective. The results from the studies are presented in this thesis together with the scientific papers this thesis is based on. Studying electrochemical gradients (concentration and potential) of large electrodes and single particles may give important information of the limitations of the material. In larger three-electrode experimental set-ups, these gradients can be studied for electrodes but single particles are not available for experimental studies to the same extent since the matrix of an electrode consist of many particles, all adding to the total gradient of the electrode. The experimental part of this thesis is based on different experimental techniques: Three-electrode experiments for larger electrodes, microelectrode experiments for single particles, numerical simulations using Multiphysics (software) of large electrodes consisting of single particles. Four Papers are appended to the thesis. They present results and discussions regarding ionic transport, surface functionalities and modeling of a particle based supercapacitor electrode. Estimated effective diffusivities for an active carbon containing micro, meso and macropores are presented. Surface functionalities in the form of oxygen-containing groups were present in a carbon studied using two experimental set-ups. Faradaic peaks, previously not reported in activated carbon were seen. The occurrence of Faradaic phenomena in one experimental set-up but not the other is further analyzed and the origin of these peaks discussed. The particle based mathematical model, where galvanostatic and cyclic voltammetry is simulated, is presented. Concentration profiles both in the particles and electrodes are discussed and some of the numerical results are compared with experimental data. / QC 20100809

<p>A digital microfluidic biochip (DMFB) is a device that digitizes fluidic samples into tiny droplets and operates chemical processes on a single chip. Movement control of droplets can be realized by using electrowetting-on-dielectric (EWOD) technology. DMFBs have high configurability, high sensitivity, low cost and reduced human error as well as a promising future in the applications of point-of-care medical diagnostic, and DNA sequencing. As the demands of scalability, configurability and portability increase, a new DMFB architecture called Microelectrode Dot Array (MEDA) has been introduced recently to allow configurable electrodes shape and more precise control of droplets.</p> <p>The objective of this work is to investigate a routing algorithm which can not only handle the routing problem for traditional DMFBs, but also be able to route different sizes of droplets and incorporate diagonal movements for MEDA. The proposed droplet routing algorithm is based on 3D-A* search algorithm. The simulation results show that the proposed algorithm can reduce the maximum latest arrival time, average latest arrival time and total number of used cells. By enabling channel-based routing in MEDA, the equivalent total number of used cells can be significantly reduced. Compared to all existing algorithms, the proposed algorithm can achieve so far the least average latest arrival time.</p>

<p>A digital microfluidic biochip (DMFB) is a device that digitizes fluidic samples into tiny droplets and operates chemical processes on a single chip. Movement control of droplets can be realized by using electrowetting-on-dielectric (EWOD) technology. DMFBs have high configurability, high sensitivity, low cost and reduced human error as well as a promising future in the applications of point-of-care medical diagnostic, and DNA sequencing. As the demands of scalability, configurability and portability increase, a new DMFB architecture called Microelectrode Dot Array (MEDA) has been introduced recently to allow configurable electrodes shape and more precise control of droplets.</p> <p>The objective of this work is to investigate a routing algorithm which can not only handle the routing problem for traditional DMFBs, but also be able to route different sizes of droplets and incorporate diagonal movements for MEDA. The proposed droplet routing algorithm is based on 3D-A* search algorithm. The simulation results show that the proposed algorithm can reduce the maximum latest arrival time, average latest arrival time and total number of used cells. By enabling channel-based routing in MEDA, the equivalent total number of used cells can be significantly reduced. Compared to all existing algorithms, the proposed algorithm can achieve so far the least average latest arrival time.</p>

Parkinson’s disease (PD) is accompanied by a significant amount of beta β-band (11Hz-30Hz) neuronal and local field potential (LFP) oscillatory activity in the subthalamic nucleus (STN). The aim of this study was to measure the spatial extent of β coherent activity in the STN and coherence between STN-SNr in PD patients OFF levodopa by systematically varying the vertical distance between two microelectrodes. We found significant β-LFP coherence across the dorsoventral extent of STN. Spatially extended beta LFP was positively correlated with the mUPDRS scores of the PD patients in the OFF state. Additionally, a significant coherence was found between β-LFPs in dorsal STN and dorsal SNr. These data suggest that the whole STN may be entrained within the β band in PD patients OFF meds. The finding of coherence between STN and SNr suggests that β oscillations synchronize both the input and output nuclei of the basal ganglia.

Parkinson’s disease (PD) is accompanied by a significant amount of beta β-band (11Hz-30Hz) neuronal and local field potential (LFP) oscillatory activity in the subthalamic nucleus (STN). The aim of this study was to measure the spatial extent of β coherent activity in the STN and coherence between STN-SNr in PD patients OFF levodopa by systematically varying the vertical distance between two microelectrodes. We found significant β-LFP coherence across the dorsoventral extent of STN. Spatially extended beta LFP was positively correlated with the mUPDRS scores of the PD patients in the OFF state. Additionally, a significant coherence was found between β-LFPs in dorsal STN and dorsal SNr. These data suggest that the whole STN may be entrained within the β band in PD patients OFF meds. The finding of coherence between STN and SNr suggests that β oscillations synchronize both the input and output nuclei of the basal ganglia.

Typescript. / Thesis (PhD)--Macquarie University (Division of Environmental & Life Sciences, Dept. of Chemistry & Biomolecular Sciences), 2005. / Includes bibliographical references. / Microelectrode voltammetry -- Experimental -- Microelectrode fabrication -- Characterisation of the carbon film surface: Surface stability - X-ray photoelectron spectroscopy - Raman spectroscopy - Capacitance - Edge plane concentration - Potential window - Surface concentration of alkenes and alkynes - Outer sphere electron transfer using hexaamineruthenium (III) chloride - Reduction of potassium hexacyanoferrate (III) - Anodic oxidation: diol to dione; dopamine and ascorbic acid - Surface oxidation - Ferrocene in a non aqueous solvent -- Selectivity: Formation of carboxylic acid groups on a carbon film surface by ferrous II sulfate complex oxidation - Ethanol modified carbon film surface - Modification of carbon film microelectrode surface using aromatic amines - Modification of carbon film surfaces to form a dual functional ascorbic acid barrier -- In vivo anti fouling properties of surface modified carbon film microelectrodes -- Conclusion. / In this thesis a procedure is presented for the fabrication of a microelectrode to monitor the neurotransmitter dopamine in vivo. The microelectrodes are fabricated by in situ pyrolysis of acetylene under a nitrogen blanket onto a quartz capillary. The carbon film was then anodically oxidised in the presence of 2,4-dinitroaniline. These microelectrodes are stable, provide the physical strength to penetrate brain tissue, have a low capacitance, are resistant to fouling in vivo and selectively suppress the endogenous ascorbic acid which oxidises at the same potential as dopamine. With such properties the carbon film microelectrode appears ideally suited for fast scanning cyclic voltammetric studies of cationic neurotransmitters such as dopamine in vivo. / xxviii, 323 p. ill

This work presents microfabricated microelectrodes, capable of quantitative analysis in molten salt (MS). MSs are an electrolytic medium of growing interest, especially in the area of nuclear reprocessing. However, designing sensors for a MS-based nuclear reprocessing system is a challenge, owing to the usually corrosive nature and high operating temperatures (typically 450 - 500◦C) of MS. Microelectrodes are well placed as sensors, with numerous advantages over macro-scale electrodes. As a consequence, there have been previous attempts to utilise microelectrodes inMS. However, these have not been successful and all have suffered disadvantages inherent in traditional microelectrode manufacturing. The microelectrodes presented in this work were produced using standard microfabrication techniques and characterised in MS. An analysis of failure mechanisms guided a systematic study of material combinations. This resulted in a sensor, which is capable of delivering quantifiable electrochemistry in MS. However, the lifetime and yield of the sensor were determined to only be 46% and 1.4 hours respectively. Further investigation of the microelectrode failure mechanisms guided several layout changes to the microelectrode design. By reducing critical area, where defects or pinholes could form, these resulted in improvements in performance. This increased the yield to 65%, while the average lifetime increased up to 45 hours. Test structures were designed to investigate the causes of the continued microelectrode failures and identified shorting between the electrode metal and silicon substrate. This suggests the existence of defects in the underlying insulator are the cause of the 35% of microelectrodes which never functioned. Separate test structures suggested the lifetimes of the microelectrodes could also be improved by removing the need for a metal adhesion layer. Tantalum has been suggested as a replacement electrode metal and a proof of concept study demonstrated the feasibility of employing thin film tantalum as an electrode metal in LKE. Using this technology as a platform, several proof-of-concept microelectrode designs are also presented: liquid microelectrodes, microelectrode arrays, and a nanoelectrode. These are targeted at specific sensing applications, and provide an expanded spectrum of measurements in MS.

abstract: Epilepsy is a group of disorders that cause seizures in approximately 2.2 million people in the United States. Over 30% of these patients have epilepsies that do not respond to treatment with anti-epileptic drugs. For this population, focal resection surgery could offer long-term seizure freedom. Surgery candidates undergo a myriad of tests and monitoring to determine where and when seizures occur. The “gold standard” method for focus identification involves the placement of electrocorticography (ECoG) grids in the sub-dural space, followed by continual monitoring and visual inspection of the patient’s cortical activity. This process, however, is highly subjective and uses dated technology. Multiple studies were performed to investigate how the evaluation process could benefit from an algorithmic adjust using current ECoG technology, and how the use of new microECoG technology could further improve the process. Computational algorithms can quickly and objectively find signal characteristics that may not be detectable with visual inspection, but many assume the data are stationary and/or linear, which biological data are not. An empirical mode decomposition (EMD) based algorithm was developed to detect potential seizures and tested on data collected from eight patients undergoing monitoring for focal resection surgery. EMD does not require linearity or stationarity and is data driven. The results suggest that a biological data driven algorithm could serve as a useful tool to objectively identify changes in cortical activity associated with seizures. Next, the use of microECoG technology was investigated. Though both ECoG and microECoG grids are composed of electrodes resting on the surface of the cortex, changing the diameter of the electrodes creates non-trivial changes in the physics of the electrode-tissue interface that need to be accounted for. Experimenting with different recording configurations showed that proper grounding, referencing, and amplification are critical to obtain high quality neural signals from microECoG grids. Finally, the relationship between data collected from the cortical surface with micro and macro electrodes was studied. Simultaneous recordings of the two electrode types showed differences in power spectra that suggest the inclusion of activity, possibly from deep structures, by macroelectrodes that is not accessible by microelectrodes. / Dissertation/Thesis / Doctoral Dissertation Bioengineering 2015

abstract: Gene manipulation techniques, such as RNA interference (RNAi), offer a powerful method for elucidating gene function and discovery of novel therapeutic targets in a high-throughput fashion. In addition, RNAi is rapidly being adopted for treatment of neurological disorders, such as Alzheimer's disease (AD), Parkinson's disease, etc. However, a major challenge in both of the aforementioned applications is the efficient delivery of siRNA molecules, plasmids or transcription factors to primary cells such as neurons. A majority of the current non-viral techniques, including chemical transfection, bulk electroporation and sonoporation fail to deliver with adequate efficiencies and the required spatial and temporal control. In this study, a novel optically transparent biochip is presented that can (a) transfect populations of primary and secondary cells in 2D culture (b) readily scale to realize high-throughput transfections using microscale electroporation and (c) transfect targeted cells in culture with spatial and temporal control. In this study, delivery of genetic payloads of different sizes and molecular characteristics, such as GFP plasmids and siRNA molecules, to precisely targeted locations in primary hippocampal and HeLa cell cultures is demonstrated. In addition to spatio-temporally controlled transfection, the biochip also allowed simultaneous assessment of a) electrical activity of neurons, b) specific proteins using fluorescent immunohistochemistry, and c) sub-cellular structures. Functional silencing of GAPDH in HeLa cells using siRNA demonstrated a 52% reduction in the GAPDH levels. In situ assessment of actin filaments post electroporation indicated a sustained disruption in actin filaments in electroporated cells for up to two hours. Assessment of neural spike activity pre- and post-electroporation indicated a varying response to electroporation. The microarray based nature of the biochip enables multiple independent experiments on the same culture, thereby decreasing culture-to-culture variability, increasing experimental throughput and allowing cell-cell interaction studies. Further development of this technology will provide a cost-effective platform for performing high-throughput genetic screens. / Dissertation/Thesis / Ph.D. Bioengineering 2012