On‐tissue chemical derivatization in mass spectrometry imaging

Abstract

Mass spectrometry imaging (MSI) combines molecular and spatial information in a valuable tool for a wide range of applications. Matrix-assisted laser desorption/ ionization (MALDI) is at the forefront of MSI ionization due to its wide availability and increasing improvement in spatial resolution and analysis speed.However, ionization suppression, low concentrations, and endogenous and methodological interferences cause visualization problems for certain molecules. Chemical derivatization (CD) has proven a viable solution to these issues when applied in mass spectrometry platforms. Chemical tagging of target analytes with larger, precharged moieties aids ionization efficiency and removes analytes from areas of potential isobaric interferences. Here, we address the application of CD on tissue samples for MSI analysis, termed on-tissue chemical derivatization (OTCD). MALDI MSI will remain the focus platform due to its popularity, however, alternative ionization techniques such as liquid extraction surface analysis and desorption electrospray ionization will also be recognized. OTCD reagent selection, application, and optimization methods will be discussed in detail. MSI with OTCD is a powerful tool to study the spatial distribution of poorly ionizable molecules within tissues. Most importantly, the use of OTCD−MSI facilitates the analysis of previously inaccessible biologically relevant molecules through the adaptation of existing CD methods. Though further experimental optimization steps are necessary, the benefits of this technique are extensive.

Profile of cryptobrachytone C accumulation in Cryptocarya pulchrinervia leaves using MALDI-MSI

“…If the compound was not well ionized and detected, it was necessary to optimize the ionization using on-tissue chemical derivatization (OTCD). OTCD can be used as a tool to study the spatial distribution of poorly ionizable molecules within tissue (Claes et al 2019;Harkin et al 2021). Derivatization was carried out in this study using Girard's reagent T (GT) (Shimma et al 2016).…”

Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues

“…The on-tissue chemical derivatization (OTCD), which is spray chemical derivatization first followed by matrix application (Harkin et al, 2021), has been used to improve ionization efficiency to effectively detect analytes directly from both fresh frozen tissue and FFPE tissue. Now OTCD has developed rapidly and used to detect many biological molecules, such as N-glycan (Nishikaze et al, 2013;Holst et al, 2016;Zhang et al, 2020;Saito et al, 2021), drugs (Barre et al, 2016, amines (Chacon et al, 2011;Manier et al, 2014), fatty acids (Wu et al, 2016;Wang et al, 2019;Iwama et al, 2021), amino acids (Toue et al, 2014;Esteve et al, 2016;Guo et al, 2020), poisons (Beasley et al, 2016), plant hormones (Enomoto et al, 2018), peptides (Franck et al, 2010), steroids (Guo et al, 2020;Angelini et al, 2021;Song et al, 2021), neurotransmitters (Ito and Hiramoto, 2019;Palanisamy et al, 2020;Shariatgorji et al, 2020), and so on.…”

Advanced tandem mass spectrometry in metabolomics and lipidomics—methods and applications

“…Although chemical derivatization is routinely employed to increase analyte stability, install isotopic markers, or improve ionization yields in metabolomics and lipidomics for both LC-MS and MSI [13,[110][111][112][113], derivatization reactions that improve structural characterization of analytes without suffering consequences of complicated sample preparation steps were rare until recently. However, the discovery by Ma and Xia [114] that light-induced Paternò-Büchi (PB) reactions can aid DB position assignments with relative ease and with inexpensive equipment has sparked the interest in chemical derivatization strategies that enable structure elucidation.…”