Integrated impedance spectroscopy biosensors
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Affinity-based biosensors, or in short biosensors, are extremely powerful and versatile analytical tools which are used for the detection of a wide variety of bio-molecules. In recent times, there has been a need for developing low-cost and portable affinity-based biosensor platforms. Such systems need to have a high density of detection sites (i.e biosensing elements) in order to simultaneously detect multiple analytes in a single sample. This has led to the creation of integrated biosensors, which make use of integrated circuits (ICs) for bio-molecular detection. In such systems, it has been demonstrated that by taking advantage of the capabilities of semiconductor and very large scale integrated (VLSI) circuit fabrication processes, it is possible to build compact miniaturized biosensors, which can be used in wide variety of applications such as in molecular diagnostics and for environmental monitoring. Among the various detection modalities for biosensors, Electrochemical Impedance Spectroscopy (EIS) permits real-time detection and has label-free detection capabilities. EIS is fully electronic in nature. Hence, it can be implemented using standard IC technologies. The versatility and ease of integration of EIS makes it a promising candidate for developing integrated biosensor platforms. In this thesis, we first examine the underlying principles of EIS method of biosensing. By analyzing an immunosensor assay as an example, we show that EIS based biosensing is a highly sensitive detection method, which can be used for the detection of a wide variety of analytes. Since EIS relies on small impedance changes in order to perform detection, it requires highly accurate models for the electrode-electrolyte systems. Hence, we also introduce a compact modeling technique for the distributed electrode-electrolyte systems with non-uniform electric fields, which is capable of modelling noise and other non-idealities in EIS. In the second part of this thesis, we describe the design and implementation of an integrated EIS biosensor array, built using a standard complementary metal-oxide-semiconductor (CMOS) process. The chip is capable of measuring admittance values as small as 10nS and has a wide dynamic range (90dB) over a wide range of frequencies (10Hz-50MHz). We also report the results obtained from the DNA and protein detection experiments performed using this chip.