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Subcellular mass spectrometry imaging of lipids and nucleotides using transmission geometry ambient laser desorption and plasma ionisation

Author

Listed:
  • Reuben S. E. Young

    (University of Wollongong)

  • Ann-Katrin Piper

    (University of Wollongong)

  • Luke McAlary

    (University of Wollongong)

  • Jayden C. McKinnon

    (University of Wollongong)

  • Jeremy S. Lum

    (University of Wollongong)

  • Jens Soltwisch

    (University of Münster)

  • Marcel Niehaus

    (Bruker Daltonics GmbH & Co. KG)

  • Shane R. Ellis

    (University of Wollongong)

Abstract

Demand for mass spectrometry imaging (MSI) technologies offering subcellular resolution for tissues and cell imaging is rapidly increasing. To accomplish this, efficient analyte ionisation is essential, given the small amounts of sample material in each pixel. Herein, we describe an atmospheric pressure transmission-geometry matrix-assisted laser desorption source equipped with plasma ionisation. By utilising a pre-staining method for sample preparation, lipid signal intensities were enhanced by an order of magnitude compared to conventional matrix-only methods, while serendipitously enabling imaging of numerous nucleotides. The system enables detection of up to 200 lipids and nucleotides in tissues at 1 µm-pixel size while informative MSI data is still obtained down to 250 nm pixel size. The use of sub-micron pixels is shown to discern subcellular features through combinations with fluorescence microscopy. This method provides a powerful tool for cellular and sub-cellular imaging of small molecules from tissues and cells for spatial biology applications.

Suggested Citation

  • Reuben S. E. Young & Ann-Katrin Piper & Luke McAlary & Jayden C. McKinnon & Jeremy S. Lum & Jens Soltwisch & Marcel Niehaus & Shane R. Ellis, 2025. "Subcellular mass spectrometry imaging of lipids and nucleotides using transmission geometry ambient laser desorption and plasma ionisation," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64604-7
    DOI: 10.1038/s41467-025-64604-7
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    References listed on IDEAS

    as
    1. Jan Philipp Menzel & Reuben S. E. Young & Aurélie H. Benfield & Julia S. Scott & Puttandon Wongsomboon & Lukáš Cudlman & Josef Cvačka & Lisa M. Butler & Sónia T. Henriques & Berwyck L. J. Poad & Steph, 2023. "Ozone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Wenbo Cao & Simin Cheng & Jing Yang & Jiaxin Feng & Wenpeng Zhang & Zishuai Li & Qinhua Chen & Yu Xia & Zheng Ouyang & Xiaoxiao Ma, 2020. "Large-scale lipid analysis with C=C location and sn-position isomer resolving power," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
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