The main goal of the proposed project is to bring our novel DNA sequencing instrument from the research stage via the development stage to the pilot project testing stage. Based on single photon detection, a novel ultra sensitive DNA sequencing instrument has been designed and constructed. The present objectives are two-fold: (l) to complete the instrument development and to deploy a pilot high-throughput automated DNA sequencing instruments capable of carrying out production scale sequencing with a more than 10-fold decrease in the use of sequencing reagents when compared with the state-of-the-art reagent consumption in commercialized instruments, and (2) to carry out extensive testing of the instrument in a large-scale sequencing production environment. The reagent economy comes from both using low volume reactions and increased read length. The instrument development will be carried out at the State University of New York, Stony Brook, and sequencing technology development will be carried out at Cold Spring Harbor Laboratory (CSHL).