DESI-MS is an emerging technique with great promise, but its application range is still being investigated. The signal is more stable for longer times than in the case of deposited samples, so the recording of mass spectrometry (MS)/MS data is simple in this case. The digestion is usually not complete hence, the presence of missed cleavage sites is typical in the peptides detected.

The spectra obtained feature ions of tryptic fragments from abundant proteins present in the tissue sample. The tryptic products can be investigated directly from the tissue using DESI. After removal of lipid constituents, the tissue can be treated with protease to degrade proteins present in the tissue. The analysis of less abundant protein constituents within a tissue sample often requires the removal of lipid species prior to analysis, similar to the situation with matrix-assisted laser desorption/ionization (MALDI). INTRODUCTIONDesorption electrospray ionization (DESI) allows in situ analysis of biological tissues. Complex ions with identical stoichiometry but different origin showed the expected difference in fragmentation characteristics, which gives direct evidence for the different mechanism of specific versus nonspecific complex ion formation.Д¬ooks RG et al., 2008, In Situ Desorption Electrospray Ionization (DESI) Analysis of Tissue Sections., CSH Protoc, Vol: 2008

Preparation of specific and nonspecific complexes containing identical building blocks was attempted. Specific and nonspecific complexes were found to show markedly different fragmentation characteristics, which can be a basis for selective detection of complexes with biological relevance. Parameters were optimized to obtain maximal selectivity for specific complexes. Behavior of biologically specific and nonspecific complexes was compared under various instrumental settings. Since the scan range of first analyzer is set well above the m/z of the ligand ion, and the CID conditions are established to permit fragmentation of only loosely bound, noncovalent complexes, the method is specific to the detection of protein-ligand complexes under described conditions. The method allows for the detection of only those ions which yield ions characteristic of the ligand molecules upon fragmentation. Mass-selected intact protein-ligand complex ions are subjected to fragmentation by means of collision-induced dissociation in the collision cell of the instrument, while the second mass analyzer is set to the m/z of protonated ligand ions or their alkali metal adducts. The new method is based on electrosonic spray ionization of samples containing protein and ligand molecules, and mass spectrometric detection using the precursor ion scanning function on a triple quadrupole instrument.

Czuczy N, Katona M, Takats Z, 2009, Selective detection of specific protein-ligand complexes by electrosonic spray-precursor ion scan tandem mass spectrometry., J Am Soc Mass Spectrom, Vol: 20, Pages: 227-237, ISSN: 1044-0305ДЄ novel mass spectrometric method for the selective detection of specific protein-ligand complexes is presented.

Odesi 2005