The use of genetic analysis in disease diagnostics is largely limited by the high costs associated with performing standard molecular biology procedures, lengthy test times, and the need for highly trained personnel. We believe that the integration of individual biochemical/analytical processes into a single miniaturized system to implement complete molecular biology protocols will lead to use of lower volumes of reagents, increased automation and rapidity in the tests—ultimately resulting in improved accessibility of disease diagnostics to the health care system.

This thesis has modularized several of the components of a genetic analysis instrument, which integrate to form a complete instrument that is capable of performing molecular biology procedure from start to finish in several minutes. The microchips perform genetic amplification (via polymerase chain reaction, PCR) and analysis/detection by laser-induced fluorescence (LIF)-capillary electrophoresis (CE). These microchips consist of integrated pneumatically-actuated valves and pumps for fluid handling, and a thin film resistive element for thermal cycling. The instrument includes a high voltage module for electrophoresis and an optical system for the excitation and detection of fluorescently labeled analytes. This integrated platform has a component cost of less than $1000. The platform presented is a major step towards practical realization of genetic testing within a clinic, or as a point-of-care device. To further simplify and miniaturize the inexpensive instrument, a fully electrically controlled phase-change microvalve was developed that simplifies the instrumentation (that operates the pneumatics) necessary for highly portable and inexpensive POC-based diagnostics.

A module for the nucleic acid extraction (i.e. sample preparation, SP) from clinical samples has been developed that is compatible for integration on a single substrate with PCR-CE functionality and also readily integrates with the instrument. Thus far SP has been tested as a stand-alone module.

During the evolution of this thesis, with our collaborators we have miniaturized the electronics infrastructure for each functional module identified in this project, and replaced them using a custom integrated circuits (CMOS/microelectronics) tailored for this application. These modules were then integrated with the microfluidics to realize a $150 fist-sized LIF-CE instrument.

Using the microchips and instruments developed, we have demonstrated applicability in diverse areas such as pathogen detection, cancer biomarker detection, and genotyping. With this project there has emerged a distinct path for future miniaturization, since each developed module is scalable. There is hence an ongoing effort to build an USB-key size medical diagnostic.