Again MALDI TOF analysis of nucleic acids with cleavable mass tags has been demonstrated by various groups (20) (21) (22) (23) (24) but it would be advantageous to be able to take advantage of lower cost ESI-MS/MS instruments and to avoid the laborious sample workup requirements of most MALDI approaches. A matrix-free laser desorption approach, which has reduced workup requirements has been demonstrated (21, 25) but this still requires that the sample be spotted onto a MALDI target or hybridized to an array. To our knowledge, only one mass tagging approach employing ESI-MS analysis has been demonstrated (26) . In this approach, mass tags are photocleavably linked to oligonucleotides and tag detection requires a photo-cleavage step and a tag isolation step outside of the mass spectrometer prior to tag detection, i.e. the workup is not much simpler than that required for MALDI TOF analysis.