The overall objective of the proposed program is the development of a prototype instrument for the automated, high speed sequencing of DNA. The project will combine state-of-the-art techniques, focusing particularly on the multiplexed sequencing and direct transfer methods pioneered by Dr. G. Church and Dr. P. Richterich at Harvard Medical School. It is expected that the combination of multiplexing and automation will reduce the cost of sequencing by a factor of 7 to 10. Specifically, the intent is to develop and commercialize a medium sized machine that combines DNA vector tagging, amplification, fragmentation, gel electrophoresis, direct transfer electrophoresis, individual probe simulation, film recording and automated reading. In Phase I the focus will be on the probe simulation function which is the most labor intensive activity and the one with the least prior development.