Understanding the structure and function of proteins has become increasingly important since the completion of the Human Genome Project and the sequencing of several other important genomes. In recent years, lab-on-a-chip systems have introduced some new capabilities for protein analyses. Rapid progress in the field of microsystems, miniaturized devices combining sensor and electronics, facilitates a new generation of miniaturized biosensor arrays utilizing silicon CMOS chips that acquire and process bio-electrochemical signals. Such biosensor array microsystems permit improved sensitivity, measurement throughput and cost per assay. This thesis research addresses the design and development of high performance electrochemical instrumentation circuits that enable simultaneous characterization of multiple protein interfaces in a high throughput chip-scale biosensor arrays microsystem. A CMOS amperometric biosensor readout circuit with current resolution of 1pA has been developed. Furthermore, a new compact, low power, 100fA current resolution impedance analysis circuit that utilizes mixed-mode signal processing to extract real and imaginary impedance components has been developed and tested with an on-chip protein interface. Moreover, to realize a multi-protein array of sensors with different instrumentation needs, a hardware efficient CMOS electrochemical circuit has been designed to achieve both amperometric and impedimetric measurement while sharing hardware source. Finally, by integrating an understanding of both protein assays challenges and microelectronics design limitations, a novel 1000-element array instrumentation architecture that permits rapid high-throughput characterization of membrane proteins with single protein resolution has been designed. The CMOS instrumentation circuitry developed in this thesis research could significantly advance proteomics research and progress in characterizing newly sequenced genomes.
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