Expansion Strategy-Driven Micron-Level Resolution Mass Spectrometry Imaging of Lipids in Mouse Brain Tissue

A novel method for enhanced resolution, termed expansion mass spectrometry imaging (Ex-MSI), has been developed for lipid mass spectrometry imaging, utilizing existing commercially available mass spectrometers without necessitating modifications. This approach involves embedding tissue sections in a swellable polyelectrolyte gel, with the target biomolecules indirectly anchored to the gel network. By employing matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), the method has realized an enhancement in spatial resolution that surpasses the conventional resolution limits of commercial instruments by approximately 4.5 folds. This enhancement permits the detailed visualization of intricate structures within the mouse brain at a subcellular level, with a lateral resolution nearing 1 μm. As a physical technique for achieving resolution beyond standard capabilities, this approach is readily adaptable and presents a powerful tool for high-definition imaging in biological research. ### Competing Interest Statement The authors have declared no competing interest.