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Updated: Feb 17, 2026

Spatial Molecular Imaging of the Glycome Using Mass Spectrometry
Published on: November 28, 2025
Multimodal MSI in Conjunction with Broad Coverage Spatially Resolved MS2 Increases Confidence in Both Molecular
Dušan Veličković, Rosalie K Chu, Alyssa A Carrell1
1Biosciences Division, Oak Ridge National Laboratory , Oak Ridge, Tennessee 37830, United States.
Abstract:
One critical aspect of mass spectrometry imaging (MSI) is the need to confidently identify detected analytes. While orthogonal tandem MS (e.g., LC-MS2) experiments from sample extracts can assist in annotating ions, the spatial information about these molecules is lost. Accordingly, this could cause mislead conclusions, especially in cases where isobaric species exhibit different distributions within a sample. In this Technical Note, we employed a multimodal imaging approach, using matrix assisted laser desorption/ionization (MALDI)-MSI and liquid extraction surface analysis (LESA)-MS2I, to confidently annotate and localize a broad range of metabolites involved in a tripartite symbiosis system of moss, cyanobacteria, and fungus. We found that the combination of these two imaging modalities generated very congruent ion images, providing the link between highly accurate structural information onfered by LESA and high spatial resolution attainable by MALDI. These results demonstrate how this combined methodology could be very useful in differentiating metabolite routes in complex systems.
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