A major focus of our laboratory has involved the attempt to apply mass spectrometry to the readout of DNA sequences. If successful, the use of the mass spectrometer could dramatically increase the speed and reliabilty of sequencing. Early work involved the use of visible laser light and frozen water as a matrix for the DNA. Spectra of the C- and G-terminated oligonucleotides obtained from the frozen water matrix are shown below.
The two spectra represent two of the four Sanger mixtures which would have to be analyzed to determine the sequence of bases in a piece of DNA. The spectra show that the resolution and sensitivity to sequence DNA with the mass spectrometer is indeed possible. However, the frozen water matrix method is not highly reproducible in its current form.