On-Tissue Chemical Derivatization in Mass Spectrometry Imaging

Carla Harkin, Karl Smith, Faye Cruickshank, Logan MacKay, Bryn Flinders, Ron Heeren, Tara C. B. Moore, Simon Brockbank, Diego Cobice

Research output: Contribution to journalReview articlepeer-review

45 Citations (Scopus)
206 Downloads (Pure)


Mass spectrometry imaging (MSI) combines molecular and spatial information in a valuable tool for a wide range of applications. Matrix-assisted laser desorption/ionization (MALDI) is at the forefront of MSI ionization due to its wide availability and increasing improvement in spatial resolution and analysis speed. However, ionization suppression, low concentrations, and endogenous and methodological interferences cause visualization problems for certain molecules. Chemical derivatization (CD) has proven a viable solution to these issues when applied in mass spectrometry platforms. Chemical tagging of target analytes with larger, precharged moieties aids ionization efficiency and removes analytes from areas of potential isobaric interferences. Here, we address the application of CD on tissue samples for MSI analysis, termed on-tissue chemical derivatization (OTCD). MALDI MSI will remain the focus platform due to its popularity, however, alternative ionization techniques such as liquid extraction surface analysis and desorption electrospray ionization will also be recognized. OTCD reagent selection, application, and optimization methods will be discussed in detail. MSI with OTCD is a powerful tool to study the spatial distribution of poorly ionizable molecules within tissues. Most importantly, the use of OTCD-MSI facilitates the analysis of previously inaccessible biologically relevant molecules through the adaptation of existing CD methods. Though further experimental optimization steps are necessary, the benefits of this technique are extensive. [Abstract copyright: © 2021 The Authors. Mass Spectrometry Reviews published by John Wiley & Sons Ltd.]
Original languageEnglish
Pages (from-to)662-694
Number of pages33
JournalMass Spectrometry Reviews
Issue number5
Early online date12 Jan 2021
Publication statusPublished (in print/issue) - 5 Aug 2022

Bibliographical note

Publisher Copyright:
© 2021 The Authors. Mass Spectrometry Reviews published by John Wiley & Sons Ltd.

Copyright 2021 Elsevier B.V., All rights reserved.


  • chemical derivatization
  • mass spectrometry imaging
  • matrix-assisted laser desorption ionization


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