SBIR-STTR Award

Genome sequencing projects and the development of "DNA chips", or high- density oligonucleotide microarrays (OMAs), allow researchers to perform high throughput genetic tests, including genome-wide expression monitoring and genotyping for disease diagnosis and prediction. Currently, the major drawbacks of the OMAs are their high cost and long lead time, which result from the photolithography process used in their manufacture. A large number of expensive masks must be fabricated to pattern the OMAs, resulting in high setup costs for each new design. The objective of this proposal is to develop a commercial instrument that uses a new technology that allows facile and economical synthesis of OMAs. This instrument would be sold to researchers interested in fabricating their own OMAs in their own laboratories at an economical price. The technology involves the creation of "virtual" masks with a microarray of mirrors controlled by a computer. Patterns of light created by the micromirror array replace the expensive photolithography masks and greatly reduce the time required to synthesize a custom OMA. Proof of principle has already been established that demonstrates the feasibility of the proposal. PROPOSED COMMERCIAL APPLICATION: Currently, oligonucleotide microarrays are very expensive (about $1,000) and only a limited variety are available. Access to the described instrument would allow any laboratory to rapidly overnight synthesize custom oligonucleotide microarrays, thus addressed the market's needs in this large, high growth field.

NimbleGen will refine its proprietary technology and manufacturing system into the Maskless Array Synthesizer System (MAS Systems). The MAS System will permit owners to rapidly produce inexpensive High Density Custom DNA Arrays (CDAs) in their own facilities to their own specifications. NimbleGen builds its arrays using photo deposition chemistry with its proprietary Maskless UV Light Projector. Texas Instruments Digital Light Processor (DLP) is at the heart of the NimbleGen Projector. The DLP employs a solid-state array of miniaturized aluminum mirrors to pattern up to 780,000 individual pixels of light. Next generation systems will produce up to 1.3 million pixels of light. The computer controlled fabricatoin process requires no human interaction once the glass substrate is placed into NimbleGen's proprietary reaction chamber. Fabrication occurs base-by-base inside the reaction chamber, eliminating the need for the clean rooms common to other array production processes. By using the Maskless UV Projector to control the patterning of UV light on the glass in the reaction chamber, NimbleGen achieves unparalleled precision and control over CDA fabrication. The MAS technology also permits unsurpassed speed - a cycle time of less than four hours - in the production of CDAs, thereby substantially reducing development time and costs. PROPOSED COMMERCIAL APPLICATION: There is a clear need for an inexpensive, rapid, and reliable method of generating and analyzing custom DNA arrays. There are strong indiciations of the proposed project's potential for commercialization, as follows: The market for DNA arrays and DNA array fabrication equipment is projected to be $318 million in 2001, growing to $1.7 billion in 2005, a CAGR of 49%