This Small Business Technology Transfer (STTR) Phase I project is to develop the instrumentation and processes to fabricate ex-novo large numbers of user-specified oligonucleotides in hours, using a proprietary tabletop production system. Oligomers will be synthesized in parallel on a glass slide using light-directed phosphoramidite chemistry with computer-controlled imaging, and then selectively eluted using a novel photosensitive release process. Maskless exposure will make possible the rapid synthesis of any number (up to > 700,000) of different sequences of 10-40 base pairs oligomers, with a user-defined tradeoff between the quantity and variety produced. Scaling up from a proof-of-principle instrument to a Massively Parallel Oligomer Synthesizer (MPOS) tool requires larger product throughput (picomoles of oligomers) which will be facilitated through the combination of an optical research study to increase the exposure area and intensity, and the evaluation of various engineered surfaces to increase the density among the oligomers.
The commercial application of this project is in the area of oligonucleotide synthesis. Successful genome sequencing programs have led to an urgent need for massive sets of different DNA oligonucleotides to be used as affinity reagents in various types of genetic tests. The current generation of DNA synthesizers are designed to produce large quantities of only a few oligonucleotides. This project proposes to develop a system capable of producing thousands of oligonucleotides on a scale compatible with high throughput genetic assays. It is expected that practically every laboratory performing molecular biology or genetic research will benefit tremendously from this project, since the use of oligonucleotide primers is basic to such fundamental and routine laboratory protocols as PCR, DNA sequencing, and site-directed mutagenesis. Specific groups in the commercial sector that will directly benefit from this project include biotechnology companies that manufacture products for genetic screening and clinical laboratories performing genetic analysis.
