The objective of the proposed research is to improve the accuracy, speed, and efficiency of DNA analysis on electrophoresis gels by using stable isotope-labeled DNA and resonance ionization (RI) detection. The technique offers the advantage of multiplexing up to 20 or more stable isotope labels. When combined with the other properties of RI detection, the technique offers the possibility of orders of magnitude improvement in the speed of DNA sequencing and mapping. In phase II, the plan is to develop chemical methods for attachment of several labels of the same isotope of tin or rare earth elements on a single DNA. Also optimization of electrophoresis materials and processes will be carried out to reduce background and improve sensitivity of the RI process. In addition, software for DNA sequencing interpretation will be optimized and DNA sequencing using multiple isotopes and multiple elements will be conducted. Using high repetition rate lasers and multiplexing, analysis of more than 10 million bases per day at $0.01 per base should be possible eventually. Direct commercial benefits of this technology would include providing service analysis and instruments to research and clinical laboratories for DNA sequencing and mapping, genetic disease and cancer diagnosis, toxicology testing, and development of improved agricultural and pharmaceutical products.
