This project will use sequencing by hybridization to develop a new method to detect mutations, allowing disease diagnoses in selected genes from a large number of individuals, in a faster, more economical and more comprehensive way than can currently be accomplished. Stable isotopes will be utilized as DNA labels to demonstrate the basic advantages of such labels and to show the multiplexing feasibility. Recently, we have demonstrated that stable isotopes function as both DNA and oligonucleotide labels and that resonance ionization spectroscopy can offer a very fast method for the detection of surface-bound DNA with a high degree of sensitivity, selectivity, spatial resolution, and analysis speed. During Phase I we will be evaluating two potentially viable detection techniques for rapid genome diagnosis using genosensor matrices: sputter-initiated resonance ionization spectroscopy (SIRIS) and laser atomization RIS (LARIS). Measurements will be made on quartz surfaces, onto which oligonucleotide sequences have been attached, to identify positively hybridized and unhybridized sites and to determine the sensitivity, efficiency, background, spatial resolution, and speed - and the interrelationships and trade-offs among them.
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