Abstract

<p indent="0mm">Recently, mass spectrometry imaging (MSI) has drawn more and more attention due to its continuous development and improvement as well as its vital role in the study of biological science. Many MSI-based strategies have been widely applied to the <italic>in situ</italic> qualitative and quantitative detection and the imaging of endogenous/exogenous molecules in tissues. Among them, matrix assisted laser desorption/ionization MSI (MALDI-MSI) and desorption electrospray ionization MSI (DESI-MSI) are generally regarded as the most commonly used two molecular imaging techniques. MSI, as a histology-based emerging molecular imaging technique, has significant advantages over other imaging techniques because it is a label-free technique which provides high sensitivity, high throughput, and molecular specificity derived from the use of mass spectrometers as detectors for a wide variety of ionized biomolecules <italic>in situ</italic> within a tissue section. But it still has obvious shortcomings in the <italic>in situ </italic>analysis of low-polarity and neutral biomolecules. The application of chemical derivatization technology in MSI is one of the most important approaches to overcome these deficiencies of MS molecular imaging. This review provides an overview of various chemical derivatization techniques used in MS analysis, such as esterification derivatization, acylation derivatization, addition reaction derivatization, substitution derivatization, oxidative derivatization, and other derivatizations, and highlights the application of these chemical derivatization methods in the <italic>in situ</italic> detection and imaging of biomolecules in tissues by MALDI-MSI and DESI-MSI. It can be predicted that with the advance progress of chemical derivatization technology, the application scope of MSI will be further expanded in the fields of spatial metabolomics, spatial lipidomics, spatial proteomics, and spatial glycomics.

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