Abstract

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a fast-growing technique for visualization of the spatial distribution of the small molecular and macromolecular biomolecules in tissue sections. Challenges in MALDI-MSI, such as poor sensitivity for some classes of molecules or limited specificity, for instance resulting from the presence of isobaric molecules or limited resolving power of the instrument, have encouraged the MSI scientific community to improve MALDI-MSI sample preparation workflows with innovations in chemistry. Recent developments of novel small organic MALDI matrices play a part in the improvement of image quality and the expansion of the application areas of MALDI-MSI. This includes rationally designed/synthesized as well as commercially available small organic molecules whose superior matrix properties in comparison with common matrices have only recently been discovered. Furthermore, on-tissue chemical derivatization (OTCD) processes get more focused attention, because of their advantages for localization of poorly ionizable metabolites and their‚ in several cases‚ more specific imaging of metabolites in tissue sections. This review will provide an overview about the latest developments of novel small organic matrices and on-tissue chemical derivatization reagents for MALDI-MSI.Graphical abstract

Highlights

  • Matrix-assisted laser desorption/ionization (MALDI) time-offlight (TOF) mass spectrometry imaging (MSI) can provide unparalleled insight into the spatial distribution of proteins [1], peptides [2], small molecules [3], lipids [4], glycans [5], and drugs [6] in tissue sections

  • The fast-evolving MALDI-MSI technique has been successfully applied in basic research, in pharmaceutical research [6], plant biology [7], food analysis [8], microbiology [9], and in clinical biomarker discovery [10]

  • Several other review papers [20, 56,57,58] have described new developments of mass spectrometric imaging, which described among other methods several MALDI-MSI approaches using ontissue chemical derivatization (OTCD), we present a comprehensive overview about recent developments in OTCD of functional groups including amine, phenolic hydroxyl, carbonyl, carboxylic acid, thiol, and double bond, for applications in the MALDI-MS imaging field (Table 2 and Figs. 3, 4, 5, 6, 7, and 8)

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Summary

Introduction

Matrix-assisted laser desorption/ionization (MALDI) time-offlight (TOF) mass spectrometry imaging (MSI) can provide unparalleled insight into the spatial distribution of proteins [1], peptides [2], small molecules [3], lipids [4], glycans [5], and drugs [6] in tissue sections. Ibrahim and coworkers [38] presented DPH as a suitable and effective matrix for imaging of lipids and fatty acids in rat and mouse brain tissues in negative ion mode. Guo and coworkers [63] combined a laser-assisted tissue transfer (LATT) technique with the CA derivatization for imaging of up to 67 small molecule metabolites including amino acids, neurotransmitters and dipeptides, and others in brain tissue sections of rats.

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