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Applications of stable isotopes in MALDI imaging: current approaches and an eye on the future

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Abstract

Matrix-assisted laser desorption/ionisation-imaging mass spectrometry (MALDI-IMS) is now an established imaging modality with particular utility in the study of biological, biomedical and pathological processes. In the first instance, the use of stable isotopically labelled (SIL) compounds in MALDI-IMS has addressed technical barriers to increase the accuracy and versatility of this technique. This has undoubtedly enhanced our ability to interpret the two-dimensional ion intensity distributions produced from biological tissue sections. Furthermore, studies using delivery of SIL compounds to live tissues have begun to decipher cell, tissue and inter-tissue metabolism while maintaining spatial resolution. Here, we review both the technical and biological applications of SIL compounds in MALDI-IMS, before using the uptake and metabolism of glucose in bovine ocular lens tissue to illustrate the current limitations of SIL compound use in MALDI-IMS. Finally, we highlight recent instrumentation advances that may further enhance our ability to use SIL compounds in MALDI-IMS to understand biological and pathological processes.

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Data availability

Bovine lens data is available upon request.

Abbreviations

MALDI:

Matrix-assisted laser desorption/ionisation

IMS:

Imaging mass spectrometry

FT-ICR:

Fourier transform ion cyclotron resonance

SIL:

Stable isotopically labelled

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Acknowledgements

The authors wish to thank the Maurice and Phyllis Paykel Trust for small equipment funding, the Health Research Council of New Zealand, the Auckland Medical Research Foundation, and the University of Auckland Mass Spectrometry Hub Strategic Research Initiative. We also acknowledge Biorender.com as the source of some artwork in Figs. 1, 3, and 6.

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Funding

Funding is provided by the Auckland Medical Research Foundation (ACG and MT: #1119015, NJD: #1119018), the Health Research Council of New Zealand (ACG and AZ: #14/015, #20/872, and #20/692), and the University of Auckland Mass Spectrometry Hub, a Strategic Research Initiative from the University of Auckland (GG).

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  1. School of Medical Sciences, University of Auckland, Auckland, 1142, New Zealand

    Angus C. Grey, Melody Tang, Ali Zahraei & George Guo

  2. School of Biological Sciences, University of Auckland, Auckland, 1142, New Zealand

    Nicholas J. Demarais

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A.C. Grey, M. Tang, and N.J. Demarais designed and drafted the manuscript. A. Demarais contributed data for the bovine lens data. G. Guo provided information for the bioinformatics section.

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Correspondence to Angus C. Grey.

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Published in the topical collection Mass Spectrometry Imaging 2.0 with guest editors Shane R. Ellis and Tiffany Porta Siegel.

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Grey, A.C., Tang, M., Zahraei, A. et al. Applications of stable isotopes in MALDI imaging: current approaches and an eye on the future. Anal Bioanal Chem 413, 2637–2653 (2021). https://doi.org/10.1007/s00216-021-03189-8

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