This Phase I research project involves the constructionof spatially defined arrays of oligonucleotide probes and the useof these arrays to study DNA sequencing by hybridization. Newlydeveloped techniques in light-directed polymer synthesis are beingapplied to the construction of oligonucleotide arrays, toexploration of kinetic and solvent-related parameters of targethybridization to the arrays, and to reading the positions ofhybridization by epifluorescence microscopy. Specificcombinatorial synthesis strategies are being designed to addressexperimental issues of parallel hybridization. Completion of thiswork will lead to sequencing instrumentation that could provideorder of magnitude improvements in DNA sequencing productivity.Anticipated Results/Potential Commercial Applications as described by the awardee:Successful completion of this project will lead toa method for rapid and inexpensive fabrication of oligonucleotidearrays. The oligonucleotide arrays can be applied to the HumanGenome effort for high throughput sequencing by hybridization, andto other efforts in genetic fingerprinting and genetic mapping. Scale-up of this technology could be used to provideoligonucleotide templates to national, university, and commerciallaboratories investigating applications of hybridizationtechnology. The oligonucleotide arrays would find commercialapplications in genetic diagnostics.
