Seeing the invisible: Preparative strategies to visualise elusive molecules using mass spectrometry imaging

Mass Spectrometry Imaging (MSI) is a powerful tool for the simultaneous visualisation and analysis of multiple molecules in complex biological samples. It provides information on their spatial distribution and is gaining increasing importance as a tool to study health and disease mechanisms. Despite its excellent multi-omics capabilities, some molecules are still not easily accessible via MSI for reasons such as low abundance or poor ionisation efficiency. However, sophisticated (bio)chemical sample treatments such as on-tissue derivatisation, enzymatic digestion, and labelling strategies have been developed to overcome these issues. In this review, we discuss advancements made in the last three decades on On-Tissue Chemical Derivatisation (OTCD), On-Tissue Enzymatic Digestion (OTED), and On-Tissue Mass Tag Labelling (OTMT) strategies, highlighting representative examples and commenting on their respective strengths and weaknesses.

Automated summary

Mass Spectrometry Imaging (MSI) is a powerful tool for visualizing and analyzing multiple molecules in complex biological samples. Despite some molecules being difficult to access through MSI, sophisticated (bio)chemical sample treatments have been developed to overcome this. This review discusses advancements made in On-Tissue Chemical Derivatisation (OTCD), On-Tissue Enzymatic Digestion (OTED), and On-Tissue Mass Tag Labelling (OTMT) strategies, highlighting their strengths and weaknesses.