The long-term objective of this research is to provide researchers with fast, inexpensive access to any DNA sequence. Gene-based research is at the heart of drug discovery today. The ability to acquire and modify genes is integral to much of the basic research supported by the NIH; research which will be the foundation of future therapeutic research. Fast and cost-effective gene synthesis has the potential to improve the speed and productivity of both applied and basic biomedical research and thus to improve healthcare very broadly. This application's specific objective is to build, test and refine an automated system capable of unattended production of 50,000 base pairs of synthetic DNA fragments in less than 18 hours. This system will first be commercialized by incorporating it into Blue Heron Biotechnology's existing automated gene synthesis process. In the future, it could be the basis for a commercial instrument for gene synthesis. The instrument will be based on the novel and innovative technologies for gene assembly developed in the Phase I portion of this research. It will involve both custom-designed instruments and the incorporation of available automation for plate handling and plate storage, novel attachment chemistry and custom-manufactured solid-phase supports. ? ?