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This System-on-Chip implementation is aimed at measuring small impedance with high accuracy. This system consists of an Analog sensor, Analog to Digital converter and a computational unit that is used to calculate the magnitude and phase of the impedance. The SoC can find its application in affinity based biosensors that use impedance spectroscopy to determine the properties of the analyte. Other applications include measuring impedances from probes buried in building structures to monitor the health of he buildings. / text

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The evaluation, analysis and development of an oxygen-insensitive amperometric glucose biosensor and its application in microbial batch culture are described. The biosensor consisted of a graphite foil electrode modified with glucose oxidase and 1,1'-dimethylferrocene, and operated via mediated electron transfer from the enzyme to the electrode. Initial evaluations illustrated several operating characteristics which would be expected to cause problems in continuous monitoring applications, most notably sensor instability and a progressive increase in response time. The main underlying causes of these unfavorable characteristics were identified as enzyme loss, mediator loss and substrate diffusion limitation within the electrode. As a consequence of these insights, further development of the sensor was undertaken. A number of different electrode materials and enzyme immobilization techniques were tested, resulting in the development of a novel immobilization procedure using a hexadecylamine coating to bind 'the activated carbohydrate residues of periodate-oxidized glucose oxidase. This improved the sensor lifetime and response time under continuous operation. Strategies for the reliable application of the biosensor in fermentation monitoring were evaluated. In-line flow cell and in_§itu membrane probe approaches were considered, and the latter approach was preferred: Considerable attention was devoted to optimising the design of such probes. The best design accommodated a three electrode configuration with a multiple biosensor array. It was found necessary to allow for periodic on-line calibration within the aseptically operating probe. This configuration was successfully applied on-line to monitor glucose in batch cultures of Escherichia coli.

Metal oxides have recently come under study thanks to their physical and electrical properties for different applications such as MOS devices, i.e. substituting the silicon oxide with a high-k material, or as MIM (Metal Insulator Metal) capacitors, to increase capacitance per unit area and circuit integration. One oxide of interest in this field is aluminum oxide since it features good electrical insulation and high dielectric constant. In-depth studies are presented here on the use of non-porous anodic Al2O3. Major physical and electrical parameters have been obtained, i.e. dielectric constant, stress, deformation, resistance, surface quality. Constant, low anodizing current density results in a denser oxide, with a thickness of around 100 nm. Performances such as capacitance, breakdown voltage, etc. can be improved when compared to other Al2O3 obtained by other methods. Results are also comparable to other high-k oxides. Fair performance is maintained for temperature raised up to 200°C, which opens new possible applications. Its mechanical and physical properties make it candidate in biological and MEMS devices. DNA re-association or hybridization is the underlining principle of DNA sensors. Different electrical Al structures protected by a thin anodic Al2O3 are tested. Interdigitated capacitors, the most promising electrical structure, were selected and process characterization performed. Three electrical extraction procedures are performed on the same device lying on a passivated silicon substrate: inter-electrodes capacitance, the self-resonance frequency, and the equivalent MOS capacitance between the short-circuited electrodes and the substrate. This study is the first of its kind to open the way for correlation studies and noise reduction techniques based on multiple electrical measurements of the same DNA hybridization event. The hybridization of concentrations as low as 50 pM target DNA has been successfully electrically detected using silver enhancement over gold nano-particles labeled DNA.

In this thesis, we study the mathematical modelling of some problems that involve surface effects. These include an optical biosensor, which uses optical principles qualitatively to convert chemical and biochemical concentrations into electrical signals. A typical sensor of this type was constructed in Badley et al., [6], and Jones et al., [18],but diffusion was considered in only one direction in [18] to simulate the reaction between the antigen and the antibody. For realistic applications, we propose the biosensor model in R3. Our theoretical approach is explicitly presented since it is simple and directly applicable to the numerical part of the thesis. In particular, we present existence and uniqueness results based on Maximum Principle and weak solution arguments. These ideas are later applied to systems and to the numerical analysis of the approximate discretized problems.It should be noted that without one dimensional symmetry, the equations can not be decoupled in order to reduce the problem to a single equation. We also show the long time monotonic convergence to the steady state. Next, a finite volume method is applied to the equations, and we obtain existence and uniqueness for the approximate solution as well as the convergence of the the first order temporal norm and the L2 spatial norm. We illustrate the results via some numerical simulations. Finally we consider a mathematically related system motivated by lagoon ecology. We show that under suitable conditions on the coecients, the system has a periodic solution under harvesting conditions. The mathematical techniques now depend on estimates for periodic parabolic problems. / Applied Mathematics

Nanofabrication has received substantial interest from scientists and engineers because of its potential applications in many fields. This was because nanoscale structures have unique properties that cannot be observed or utilized at other size scales. Our living environment and many of our daily necessities had been strongly influenced by these techniques. Computers, electronics, housewares, vehicles, and medical care are now all affected by this explosive nanotechnology. However, traditional methods in controlling nanoscale features and their properties were often time-consuming and expensive. The objective of my research was to design, fabricate, and test nanostructure platforms using a unique toolbox of bottom-up lithographic techniques recently developed in our laboratory. These novel methods can be utilized for the rapid prototyping of nanoscale patterns in a much easier and more economical way. Specifically, we also focused on applying these nanoscale patterns as sensor platforms. These platforms were easily produced with our unique methods, and provide ultra sensitive capability to detect diverse chemical or biological species. The demonstration of capabilities and applications of our unique technologies includes the following projects. Chapters II and III describe a simple, inexpensive, and rapid method for making metal nanoparticles ranging between 10 nm and 100 nm in size through metal photoreduction with templates. The process can be completed in approximately 11 minutes without the use of a clean room environment or vacuum techniques. A simple label-free biosensor fabrication method based on transmission localized surface plasmon resonance (T-LSPR) of this platform is also demonstrated. Chapters IV and V present a nanoscale patterning technique for creating diverse features in polymers and metals. The process works by combining evaporative ring staining with a colloidal templating process. Well-ordered hexagonally arrayed nanorings, double rings, triple rings, targets, and holes were all easily prepared. A line width as thin as ~15 nm can repeatably be performed with this technology. Finally, Chapter VI demonstrates an ultra-sensitive plasmonic optical device based on hexagonal periodic nanohole metal films produced through our evaporative templating technique. The optical properties of these sub-wavelength periodic hole array metal films are discussed.

The objective of this research was to develop the initial constituents of a highly scalable and label-free electronic biosensing platform. Current immunoassays are becoming increasingly incapable of taking advantage of the latest advances in disease biomarker identification, hindering their utility in the potential early-stage diagnosis and treatment of many diseases. This is due primarily to their inability to simultaneously detect large numbers of biomarkers. The platform presented here - termed the electronic microplate - embodies a number of qualities necessary for clinical and laboratory relevance as a next-generation biosensing tool. Silicon nanowire (SiNW) sensors were fabricated using a purely top-down process based on those used for non-planar integrated circuits on silicon-on-insulator wafers and characterized in both dry and in biologically relevant ambients. Canonical pH measurements validated the sensing capabilities of the initial SiNW test devices. A low density SiNW array with fluidic wells constituting isolated sensing sites was fabricated using this process and used to differentiate between both cancerous and healthy cells and to capture superparamagnetic particles from solution. Through-silicon vias were then incorporated to create a high density sensor array, which was also characterized in both dry and phosphate buffered saline ambients. The result is the foundation for a platform incorporating versatile label-free detection, high sensor densities, and a separation of the sensing and electronics layers. The electronic microplate described in this work is envisioned as the heart of a next-generation biosensing platform compatible with conventional clinical and laboratory workflows and one capable of fostering the realization of personalized medicine.