Laser desorption mass spectrometry for ultrafast DNA analysis and its applications

Summary form only given. In order to use mass spectrometry for fast DNA sequencing, there are three requirements: (1) detection of large DNA segments, (2) detection sensitivity in the femtomole region, and (3) resolution must be good enough to resolve DNA sizes of one nucleotide difference. With pulsed ion extraction, mass resolution of more than 1000 has been achieved for small DNA segments. If good resolution can be extended to large DNA segments, sequencing the human genome will become possible. In addition to using laser desorption mass spectrometry for human genome sequencing, we also used LDMS for genetic disease diagnosis. Cystic fibrosis DNA is characterized by the deletion of three nucleotides that code phenylalanine in the 508 position of the cystic fibrosis transmembrane conductance regulator. We recently succeeded in using LDMS to detect the codon 508 mutant in cystic fibrosis carriers and patients.