Obtaining sequence information of the human genome will provide the necessary genetic data base for the next generation of gene based therapies of a wide variety of diseases. Achieving this ambitious goal will require improvements in existing technology and development of new technologies to allow for high speed gene sequencing. Fragmentation of parent ions represents one of the major obstacles to the development of mass spectrometry for rapid size analysis required for DNA sequencing. Ion fragmentation can limit the size of detectable ionized oligonucleotides and lead to a loss of mass-spectral resolution, both essential requirements for high speed sequencing with long read lengths. Recent studies in the investigator's laboratory have shown that ion fragmentation may be drastically slowed by rapid evaporative cooling using van der Waals clusters. Feasibility studies are proposed to test whether rapid evaporative cooling may be used to suppress fragmentation in mass spectrometry of DNA oligomers. A major goal of the proposed research is to demonstrate mass spectra of DNA containing between approximately 500-1000 nucleotides with resolution (=m/delta m) better than 1000. Ability to obtain such high resolution mass spectra could enable high speed sequencing with read lengths as long as that presently available with electrophoresis. Even conservative estimates suggest that this would mean a speeding up of the DNA separation and sizing step by two orders of magnitude as well as an improvement in accuracy.