This proposal relates to the automated simultaneous chemical synthesis of large numbers of high quality oligonucleotides at a total throughput greater than four bases per minute using beta-cyanoethyl phosphoramidite chemistry, and reagent usage at a fraction of conventional automated DNA synthesizers. One goal of this Phase II research is to fabricate a fully automated, multiple DNA synthesizer capable of producing 40 - 60 oligonucleotides simultaneously at 0.02 - 0.2 umol scale, reducing the reagent cost per base addition from the current $1.00 to $2.00 (0.2 umol scale of synthesis by conventional DNA synthesizers) to under 50 cents.The performance capability of the automated machine with its faster production time and lower cost of production should dramatically reduce the cost and time associated with research projects requiring numerous oligonucleotides. Besides fabricating a fully automated system which could be produced at a cost affordable to researchers, another Phase II objective is to produce a higher throughput, semiautomated instrument for the HGP, for example oligonucleotide libraries, STS primer, repository and oligonucleotide arrays. The Phase II research is expected to stimulate further technology development in the HGP.
