Improving the speed and efficiency of DNA sequencing is essential to the success of the Human Genome Project and to the success of many biotechnology companies. Limitations due to the speed and cost of DNA sequencing are inhibiting new ways of integrating molecular biology and biomedical research to reduce health care costs. Our goal is dramatically to increase the speed and efficiency of Sanger sequencing primarily through adoption of microfabrication techniques. We will create a working prototype microfabricated separation module, load interfacing protocol, and software which can be integrated with our existing modular optical platform. This will allow analysis of 96 samples within four hours: from genomic or other unpurified DNA sources to proofread sequence data. CuraGen has expertise in the physical, computational and biological sciences, and collaborates with the National Nanofabrication Facility and medical community. This combines with the coexistence of instrument/software development and application-driven sequencing demand to put us in a unique position to conceive and carry out this effort. Phase III commercial potential accrues not only from the current market for DNA sequencing capability, buy also from entirely new pharmaceutical, diagnostic and clinical markets which a reliable, high-throughput low-cost device would enable. PROPOSED COMMERCIAL APPLICATION: The development of a modular DNA sequencing machine with ultrahigh throughput would make possible simultaneous reductions in reagent, personnel and instrument costs. Such a development would have enormous commercial potential in its own right. This value will be greatly outweighed by the impact on the health care industry of the data generated by use in medical research. The modular nature of the instrument proposed here will add value to the existing instrument base.