Highly Parallel Oligo Synthesizer for DNA Sequencing

Using current methods for sequencing DNA, billions of dollars will be required to sequence theentire human genome. The development of new techniques is much more likely to produce a costeffective means of meeting the goals of the Human Genome Project. One important component ofassembling a sequencing reaction is to step along a DNA fragment using an oligonucleotide to prime thenext portion of the sequencing reaction. This type of oligonucleotide priming only requires about 5picomoles of oligomer; conventional synthesizers produce more than 10,000 times that amount. Thisproject involves the development of a synthesizer that can produce smaller quantities appropriate forsequencing at costs that are an order of magnitude lower than conventional systems. The projectcombines recent advancements in low cost parallel synthesis of oligonucleotides with advancedcomputer 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 littleoperator intervention and has small reagent costs. The phase I project will involve a close cooperationbetween 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 forsequencing, design of a loading/unloading system for glass beads, developing a fast, automated cleavageand deprotection system, and developing a design for a phase II instrument. The phase III project willentail the commercialization of a parallel automated oligonucleotide synthesizer, which, if successful,can produce oligonucleotides at less than 1/20 the cost of conventional systems.