MS imaging-guided microproteomics for spatial omics on a single instrument

Mass spectrometry imaging (MSI) allows investigating the spatial distribution of chemical compounds directly in biological tissues. As the analytical depth of MSI is limited, MSI needs to be coupled to more sensitive local extraction-based omics approaches to achieve a comprehensive molecular characterization. For this it is important to retain the spatial information provided by MSI for follow-up omics studies. It has been shown that regiospecific MSI data can be used to guide a laser microdissection system (LMD) for ultra-sensitive LC-MS analyses. So far, this combination has required separate and specialized MS instrumentation. Recent advances in dual-source instrumentation, harboring both MALDI and ESI sources, promise state-of-the-art MSI and liquid-based proteomic capabilities on the same MS instrument. In this study, we demonstrate that such an instrument can offer both, fast lipid-based MSI at high mass- and high lateral resolution, and sensitive LC-MS on local protein extracts from the exact same tissue section.