Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging for Peptide and Protein Analyses: A Critical Review of On-Tissue Digestion

Berta Cillero-Pastor*, Ron M. A. Heeren

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has established itself among the plethora of mass spectrometry applications. In the biomedical field, MALDI-MSI is being more frequently recognized as a new method for the discovery of biomarkers and targets of treatment, classification of diseased and healthy tissues, or prediction of the outcome of a pathology. The technology has been used to study the localization of proteolytic peptides directly on tissue sections. A direct correlation between the detected peptides and the distribution and identity of the original precursor protein is the ultimate goal of any MALDI-MSI experiment. Enzymatic digestion protocols are commonly used to reveal the protein signature of these complex tissues. Considerations that pertain to methods of sample preparation, on-tissue digestion, data analysis, and visualization will be addressed. This review will also discuss selected applications of on-tissue digestion combined with the MALDI-MSI technology in biomedicine.
Original languageEnglish
Pages (from-to)325-335
JournalJournal of Proteome Research
Issue number2
Publication statusPublished - Feb 2014


  • enzymatic digestion
  • biomarker discovery
  • pathology
  • peptide
  • protein
  • imaging
  • technology

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