On-tissue chemical derivatization reagents for matrix-assisted laser desorption/ionization mass spectrometry imaging

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a key tool for the analysis of biological tissues. It provides spatial and quantitative information about different types of analytes within tissue sections. Despite the increasing improvements of this technique, the low detection sensitivity of some compounds remains an important challenge to overcome. Poor sensitivity is related to weak ionization efficiency, low abundance of analytes and matrix ions, or endogenous interferences. On-tissue chemical derivatization (OTCD) has proven to be an important solution to these issues and is increasingly employed in MALDI MSI studies. OTCD reagents, synthesized or commercially available, have been essentially used for the detection of small exogenous or endogenous molecules within tissues. Optimally, an OTCD reaction is performed in mild conditions, in an acceptable range of time, preserves the integrity of the tissues, and prevents the delocalization. In addition to their reactivity with a targeted chemical function, some OTCD reagents can also be used as a matrix, which simplifies the sample preparation procedure. In this review, we present an exhaustive overview of OTCD reagents and methods used in MALDI MSI studies.

Automated summary

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a crucial tool for analyzing biological tissues, providing spatial and quantitative information about different analytes. However, low detection sensitivity of some compounds remains a challenge, which can be addressed by on-tissue chemical derivatization (OTCD) methods, commonly used for detecting small exogenous or endogenous molecules. OTCD reagents can also simplify sample preparation by serving as a matrix in addition to reacting with targeted chemical functions.