System Design for Development of a Massively Parallel Oligonucleotide Synthesizer for the Production of Genome Scale Reagent Sets in Pico-Molar Quantities

75788-Success in sequencing the genomes of an ever expanding number of organisms has led to an increased demand for genome scale reagent sets, needed to facilitate the further study of gene expression and genetic polymorphisms. However, the lack of an economical and rapid-turnaround supply of user-specified oligomers limits many large-scale genomic studies. This project will develop technology for producing, within hours of ordering, large libraries of thousands of oligomers in the range of 10-20 pmole per oligomer. The oligomers will be synthesized in parallel, using light-directed phosphoramidite chemistry with computer-controlled imaging, on dense arrays of silicon microwells packed with single large-area ¿controlled pores glass¿ (CPG). Phase I will design a novel high throughput, scaleable reaction cell for oligomer synthesis based on the proven Maskless Array Synthesizer. Specific tasks include: (1) optimization of the microwells design by modeling the fluid patterns in the system, (2) design and fabrication of the silicon microwell chip for oligonucleotide synthesis, and (3) development of a fluidic system for packing the CPG beads into the microwells. Commercial Applications and Other Benefits as described by the awardee: Completion of the Human Genome Project has accelerated efforts to identify thousands of genetic mutations associated with human diseases. However, many genetic assays are limited by the cost and scale of current oligonucleotide synthesis methods. The technology developed in this project would support custom genetic assays capable of screening for thousands of genetic mutations at substantially lower cost.