Recent developments of novel matrices and on-tissue chemical derivatization reagents for MALDI-MSI

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Recent developments of novel matrices and on-tissue chemical derivatization reagents for MALDI-MSI Qiuqin Zhou 1 & Annabelle Fülöp 1 & Carsten Hopf 1 Received: 13 August 2020 / Revised: 17 October 2020 / Accepted: 22 October 2020 # The Author(s) 2020

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. Keywords MALDI-MSI . MALDI matrix . MALDI imaging . On-tissue chemical derivatization . Tissue preparation

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. 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]. In short, typical MALDI-MSI workflows contain the following three steps: tissue preparation, data acquisition, and data analysis. The “4S-criteria” for a desirable MSI experiment [6], namely speed, specificity, spatial resolution, and Published in the topical collection Mass Spectrometry Imaging 2.0 with guest editors Shane R. Ellis and Tiffany Siegel Porta. * Carsten Hopf [email protected] 1

Center for Mass Spectrometry and Optical Spectroscopy (CeMOS), Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163 Mannheim, Germany

sensitivity, often cannot be achieved together, and compromises are required for MALDI-MSI methods. Although developments of mass spectrometer hardware have a great impact on the performance of MALDI-MSI, proper tissue preparation [11–14] is key for high-quality data acquis