RT Journal Article SR Electronic T1 Gel-assisted mass spectrometry imaging JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.06.02.543480 DO 10.1101/2023.06.02.543480 A1 Yat Ho Chan A1 Koralege C. Pathmasiri A1 Dominick Pierre-Jacques A1 Stephanie M. Cologna A1 Ruixuan Gao YR 2023 UL http://biorxiv.org/content/early/2023/06/03/2023.06.02.543480.abstract AB Compatible with label-free detection and quantification, mass spectrometry imaging (MSI) is a powerful tool for spatial investigation of biomolecules in intact specimens. Yet, the spatial resolution of MSI is limited by the method’s physical and instrumental constraints, which often preclude it from single-cell and subcellular applications. By taking advantage of the reversible interaction of analytes with superabsorbent hydrogels, we developed a sample preparation and imaging workflow named Gel-Assisted Mass Spectrometry Imaging (GAMSI) to overcome these limits. With GAMSI, the spatial resolution of lipid and protein MALDI-MSI can be enhanced severalfold without changing the existing mass spectrometry hardware and analysis pipeline. This approach will further enhance the accessibility to (sub)cellular-scale MALDI-MSI-based spatial omics.Competing Interest StatementR.G. is a co-inventor on multiple patents related to expansion microscopy. The other authors declare that they have no competing interests.