Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) for in situ analysis of endogenous small molecules in biological samples

Endogenous small molecules play important roles in biological processes and are closely related to the occurrence and development of many diseases. Profiling of spatial distribution of small molecules is indispensable for understanding their biological roles and elucidating disease mechanisms. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI), a robust tool for in situ analysis of various molecules simultaneously with high sensitivity in a single run, has been more and more widely used in biomedical field. This paper first gave an introduction of small molecules and MSI. Then critical issues in the workflow of MALDI MSI, including sample collection, matrix selection and disposition, and instrument were detailed described. On this basis, applications of MALDI MSI in biological field including biomarker discovery, disease mechanism investigation, cell metabolism, host-micro interaction, lipids isomeric resolution etc., were summarized. Finally, the challenges and the perspectives of MALDI MSI of small molecules are concluded and proposed. • Past development and latest progress in MALDI matrix, matrix disposition method and instrumentation were summarized and detailed described. • Applications of MALDI MSI in various aspects of biological field were reviewed. • Challenges and the perspectives of MALDI MSI in analysis of small molecules were concluded and proposed.