Nano-DESI Mass Spectrometry Imaging of Proteoforms in Biological Tissues with High Spatial Resolution

Overview

Journal Anal Chem

Specialty Chemistry

Date 2023 Mar 14

PMID 36917636

Authors

Manxi Yang

Daisy Unsihuay

Hang Hu

Frederick Nguele Meke

Zihan Qu

Zhong-Yin Zhang

Julia Laskin

Affiliations

Soon will be listed here.

Abstract

Mass spectrometry imaging (MSI) is a powerful tool for label-free mapping of the spatial distribution of proteins in biological tissues. We have previously demonstrated imaging of individual proteoforms in biological tissues using nanospray desorption electrospray ionization (nano-DESI), an ambient liquid extraction-based MSI technique. Nano-DESI MSI generates multiply charged protein ions, which is advantageous for their identification using top-down proteomics analysis. In this study, we demonstrate proteoform mapping in biological tissues with a spatial resolution down to 7 μm using nano-DESI MSI. A substantial decrease in protein signals observed in high-spatial-resolution MSI makes these experiments challenging. We have enhanced the sensitivity of nano-DESI MSI experiments by optimizing the design of the capillary-based probe and the thickness of the tissue section. In addition, we demonstrate that oversampling may be used to further improve spatial resolution at little or no expense to sensitivity. These developments represent a new step in MSI-based spatial proteomics, which complements targeted imaging modalities widely used for studying biological systems.

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