Redox enzyme based electrochemical biosensors provide label-free continuous monitoring of biomolecules. This thesis work aims to solve the key challenges in constructing a microsystem that integrates enzyme-based electrochemical sensors, electrode arrays, CMOS instrumentation circuits, and microfluidics. A CMOS compatible enzyme immobilization technique based on conductive polymers is introduced and demonstrated through a biosensor based on an alcohol dehydrogenase enzyme. Utilizing a thorough study of the cross-disciplinary compatibility requirements for on-CMOS electrochemical sensors, a microfabricated electrode array scheme is identified and further optimized through a concentric ring working electrode design that minimizes electrode area and processing complexity. A new CMOS bipotentiostat architecture is introduced which, when used in conjunction with the concentric ring electrodes, implements an electrochemical interrogation scheme that enables signal amplification through the redox recycling with enzyme modified electrodes. Finally, a novel lab-on-CMOS integration platform is introduced that unites the capabilities of lab-on-chip microfluidic systems with the performance advantages of CMOS microsystems to integrated bios. This work establishes a miniaturized platform for integrating a variety of enzymes as biosensing elements that can be utilized to analyze biological samples using powerful electrochemical techniques. By integrating significant developments in enzyme immobilization, CMOS compatible microelectrode arrays, and CMOS instrumentation for redox recycling, this research advances the fields of point-of-care medical diagnostics, high-throughput screening, and a wide range of additional sensing applications.
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