Using current methods for sequencing DNA, billions of dollars will be required to sequence the entire human genome. The development of new techniques is much more likely to produce a cost effective means of meeting the goals of the Human Genome Project. One important component of assembling a sequencing reaction is to step along a DNA fragment using an oligonucleotide to prime the next portion of the sequencing reaction. This type of oligonucleotide priming only requires about 5 picomoles of oligomer; conventional synthesizers produce more than 10,000 times that amount. The proposed project involves the development of a synthesizer that can produce smaller quantities appropriate for sequencing at costs that are an order of magnitude lower than conventional systems. The proposed project combines recent advancements in low cost parallel synthesis of oligonucleotides with advanced computer controlled machinery. Using the pin array parallel synthesizer concept developed by Dr. George Church, the plan is to design a completely integrated synthesizer instrument that requires little operator intervention and has small reagent costs. The phase I project will involve a close cooperation between academic and small business researchers and will generate an initial design for the instrument. The phase I objectives include developing a set of requirements for oligonucleotide synthesis for sequencing, design of a loading/unloading system for glass beads, developing a fast, automated cleavage and deprotection system, and developing a design for a phase II instrument. The phase III project will entail the commercialization of a parallel automated oligonucleotide synthesizer, which, if successful, can produce oligonucleotides at less than 1/20 the cost of conventional systems.
