Enhanced On-Tissue Chemical Derivatization with Hydrogel Assistance for Mass Spectrometry Imaging

Abstract

The improvement of on-tissue chemical derivatization for mass spectrometry imaging (MSI) of low-abundance and/or poorly ionizable functional molecules in biological tissue without delocalization is challenging. Here, we developed a novel hydrogelassisted chemical derivatization (HCD) approach coupled with airflow-assisted desorption electrospray ionization (AFADESI)-MSI, allowing for enhanced visualization of inaccessible molecules in biological tissues. The derivatization reagent Girard's P (GP) reagent was creatively packaged into a hydrogel to form HCD blocks that have reactivity to carbonyl compounds as well as the feasibility of "cover/uncover" contact mode with tissue sections. The HCD blocks provided a favorable liquid microenvironment for the derivatization reaction and reduced matrix effects from derivatization reagents and tissue without obvious molecular migration, thus improving the derivatization efficiency. With this methodology, unusual carbonyl metabolites, including 166 fatty aldehydes (FALs) and 100 oxo fatty acids (FAs), were detected and visualized in rat brain, kidney, and liver tissue. This study provides a new approach to enhance chemical labeling for in situ tissue submetabolome profiling and improves our knowledge of the molecular histology and complex metabolism of biological tissues.

X-dimensional Mass Spectrometry Imaging Discovers Spatially Resolved Metabolic Response

“…In this study, the AFADESI-MSI was introduced to implement spatial metabolomics data acquisition. After a decade of efforts in its hardware upgrading 29,30 , software development 40,41 , and methodology studies 42,43,44,45 , the detection sensitivity improvement has been remarkably achieved on this platform to widely cover various types of metabolites. In the drug's anti-tumor efficacy study, there were 869 target metabolites (1816 positive and negative ions) involved in 62 different types of metabolism pathways, species, and biotransformation in the metabolite ion library.…”

Advances in ionisation techniques for mass spectrometry‐based omics research

“…providing the ability to differentiate between unsaturated lipid isomers [58]. Abliz and coworkers combined AFADESI with a reagent-spiked hydrogel derivatisation methodology, allowing for a large number of metabolites and lipids to be identified from a rat brain [59].…”

Contemporary Research Progress on the Detection of Polycyclic Aromatic Hydrocarbons

“…Furthermore, there is another outstanding mass spectrometry technique, mass spectrometry imaging [ 148 , 149 , 150 , 151 , 152 ], which can play a significant role in promoting the studies of PHAs. Compared with those common mass spectrometry techniques, mass spectrometry imaging can not only get the content information of PAHs throughout the whole sample, but also obtain the information about the distribution of PAHs on a media surface.…”