However, past attempts at applying mass spectrometry to genome research were unsuccessful because no one could vaporize molecules as large as a typical DNA fragment. The most promising approach so far, they believe, is matrix- assisted laser desorption, which, potentially, could handle fragments as long as 2,000 base pairs. The matrix is an ultraviolet radiation-absorbing material that is mixed with the DNA fragments. When a pulsed UV laser zaps the mixture, the matrix absorbs the light's energy. Since velocity decreases with an increase in mass, the smaller fragments reach the detector first.
Flight time is determined by counting the flashes of pulsed laser light.
Benner says there are limitations with the detectors now available that require repeated analysis of a sample to accumulate a useful mass spectrum when matrix-assisted laser desorption is used to ionize the DNA fragments. So far, ions generated by an electrospray possess a multiplicity of charge that makes the resulting mass spectra confusing and difficult to interpret. To overcome these problems, Benner and Jaklevic plan to test new types of ion detectors on macromolecules prepared by the biologists at the Human Genome Center. These new detectors will be based on either high voltage ion acceleration, secondary ion emission, or a combination of both. Genome Center director Rine told the site reviewers that the challenge of sequencing by mass spectrometry is to be able to resolve the mass of, for example, the 300th base from the base at 299 with sufficient precision to know if the 300th base is guanine, adenine, thymine, or cytosine.