Mass spectrometric imaging (MSI) provides an attractive opportunity to detect and probe the molecular content of tissues in an anatomical context. This technique creates distribution maps of select compounds without the need for priori knowledge of target analytes. In this presentation, I will describe our efforts and recent progress in mapping and imaging of a wide variety of signaling molecules in several biological systems, highlighting the unique challenges and important roles of MSI in the areas of proteomics/peptidomics, glycomics, and lipidomics. Experimental workflow for spatial proteomics integrating MSI with label-free proteomics will be presented for mapping the spatial distribution and quantify the levels of proteins in several key brain regions in a mouse model of Fragile X syndrome. This integrated workflow enabled more than 1000 unique peptides spatially resolved, demonstrating the diverse array of peptidomes present in the tissue slices. To further improve the sensitivity of MALDI MSI, a nanosecond photochemical reaction (nsPCR) strategy has been developed to enable enhanced analyte identification and visualization from complex tissue samples through on-demand removal of surrounding matrices within nanoseconds. The utility of this new approach for in situ analysis of endogenous biomolecules is evaluated and demonstrated. Spatial visualization of glycans within clinical tissue samples represent another area of emerging applications in MALDI MSI. Herein, we develop an on-tissue derivatization strategy for sensitive mapping of N-glycans from formalin-fixed paraffin-embedded (FFPE) tissue sections, based on amidation of sialic acid residues with aniline. MSI of N-glycans on human laryngeal cancer FFPE tissue sections revealed enhanced detection of sialylated N-glycans upon amidation derivatization, showing N-glycan dysregulation in the tumor region. Additionally, a novel approach employing peracetic acid (PAA) induced epoxidation coupled with MS for localization of double bonds in unsaturated fatty acids is developed, enabling both quantification and spatial visualization of fatty acid isomers in complex biological samples ranging from human cell lines to cancer tissue samples. Finally, progress towards single-cell lipidomics will be highlighted and presented.

On-tissue spatially resolved multiomics analyses enabled by MALDI mass spectrometry imaging (MSI) coupled with in situ chemical reactions

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.