Project Brief
Tools For DNA Diagnostics (October 1994)DNA Diagnostic Systems Based on Novel Chem-jet TechniquesDevelop a method akin to ink-jet printing for synthesizing large arrays of specific DNA fragments suitable for medical diagnosis, microbial detection and DNA sequencing, and for creating supplies of detachable oligonucleotides for subsequent use. Sponsor: Incyte Genomics (formerly Combion,Inc./Incyte Pharm.Inc.)400 Seaport CourtRedwood City, CA 94063
Combion, Inc., proposes to develop a new molecule-making process called "Chem-jet" as the heart of four classes of commercial DNA diagnostic and analytical products. In the "Chem-jet" technique, which was invented at the California Institute of Technology, tiny volumes of reagent-bearing liquid are squirted onto specific spots, or addresses, of a solid substrate much as an ink-jet printer squirts tiny dots onto a page. By repeatedly returning to each address with one or another of a small set of building blocks, in this case nucleotides modified for the process, huge two-dimensional libraries of short DNA chains (oligonucleotides) can be assembled. Three potential products based on these Chem-jet arrays focus on identifying specific DNA sequences in a sample. One would identify genetic defects by exposing DNA in medical samples to Chem-jet created replicas of the defective regions of disease-related genes. DNA in the sample that bonds, or hybridizes, to those replicas would serve as a diagnosis for the genetic disorder. Another product will detect micro-organisms by analyzing the overall pattern of hybridization of microbial DNA to the different DNA fragments in the array. The goal for the mathematically intense third product is to fully sequence previously unanalyzed genetic samples. The strategy is to create exhaustive oligonucleotide libraries (65,536 for lengths of 8 nucleotides), allow many fragments of the unknown DNA to hybridize where they will on the array, and then reconstruct the sample DNA sequence using clues from the known oligonucleotide sequences at each hybridized address. The fourth commercial product is different from the other three in that the oligonucleotides in the array would be deliberately detachable for subsequent uses for those who need specific oligonucleotides that are not linked to a substrate.
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