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TEMI: tissue-expansion mass-spectrometry imaging

Hua Zhang, Lang Ding, Amy Hu, Xudong Shi, Penghsuan Huang, Haiyan Lu, Paul W. Tillberg, Meng C. Wang, Lingjun Li

2025Nature Methods37 citationsDOIOpen Access PDF

Abstract

The spatial distribution of diverse biomolecules in multicellular organisms is essential for their physiological functions. High-throughput in situ mapping of biomolecules is crucial for both basic and medical research, and requires high scanning speed, spatial resolution, and chemical sensitivity. Here we developed a tissue-expansion method compatible with matrix-assisted laser desorption/ionization mass-spectrometry imaging (TEMI). TEMI reaches single-cell spatial resolution without sacrificing voxel throughput and enables the profiling of hundreds of biomolecules, including lipids, metabolites, peptides (proteins), and N-glycans. Using TEMI, we mapped the spatial distribution of biomolecules across various mammalian tissues and uncovered metabolic heterogeneity in tumors. TEMI can be easily adapted and broadly applied in biological and medical research, to advance spatial multi-omics profiling.

Topics & Concepts

Mass spectrometry imagingMass spectrometryChemistryComputational biologyChromatographyBiologyMass Spectrometry Techniques and ApplicationsMetabolomics and Mass Spectrometry StudiesAdvanced Proteomics Techniques and Applications
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