Protein analysis by desorption electrospray ionization mass spectrometry

Abstract This review presents progress made in the ambient analysis of proteins, in particular by desorption electrospray ionization‐mass spectrometry (DESI‐MS). Related ambient ionization techniques are discussed in comparison to DESI‐MS only to illustrate the larger context of protein analysis by ambient ionization mass spectrometry. The review describes early and current approaches for the analysis of undigested proteins, native proteins, tryptic digests, and indirect protein determination through reporter molecules. Applications to mass spectrometry imaging for protein spatial distributions, the identification of posttranslational modifications, determination of binding stoichiometries, and enzymatic transformations are discussed. The analytical capabilities of other ambient ionization techniques such as LESA and nano‐DESI currently exceed those of DESI‐MS for in situ surface sampling of intact proteins from tissues. This review shows, however, that despite its many limitations, DESI‐MS is making valuable contributions to protein analysis. The challenges in sensitivity, spatial resolution, and mass range are surmountable obstacles and further development and improvements to DESI‐MS is justified.