Top-Down Sequencing of Intact Proteins by MALDI In Source Decay (ISD)

Although MALDI mass spectrometry is a soft ionization technique which enables desorption of high molecular weight biomolecules exceeding several hundred kDa, it became apparent that some analyte fragmentation occurs during the MALDI process as well. The processes of fragmentation initially characterized on MALDI-TOF mass spectrometers were designated as either; (i) in-source decay (ISD), the combination of laser-induced fraqmentation and rapidly-occurring metastable decay, or (ii) post-source decay (PSD), the metastable decay occurring during TOF mass separation. Both the ISDmethod and PSD-method were used to obtain primary sequence information on peptides and small proteins. On modern TOF/TOF systems the terminology cannot be simply applied, due to the complex ion optics of the TOF section after the ionization source. Unimolecular or metastable decay may for example be used to describe the PSD-type processes active on TOF/TOF systems.