Advances in Spatial Multi‐Omics: A Review of Multi‐Modal Mass Spectrometry Imaging and Laser Capture Microdissection‐LCMS Integration

Mass spectrometry has long been utilized to characterize a variety of biomolecules such as proteins, metabolites, and lipids. Most MS-based omics studies rely on bulk analysis; however, bulk approaches often overlook low-abundance molecules that may exert critical biological effects. Recently, multi-omics analyses have been driving an explosion of knowledge about how biomolecules interact within biological systems. In particular, spatial multi-omics has emerged as a groundbreaking approach for implementing multi-omic and multi-modal analyses. Broadly defined, spatial omics has the ability to analyze biomolecules within their native spatial contexts, offering transformative insights. This review focuses on mass spectrometry-based spatial omics, specifically matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). We will explore how MALDI-MSI, in combination with laser capture microdissection (LCM) and traditional liquid chromatography-mass spectrometry (LC-MS) workflow, is advancing spatially resolved multi-omics research.