Highly Multiplexed Immunohistochemical MALDI-MS Imaging of Biomarkers in Tissues.

PMID:33631930

IF: 3.262

Cited by: 29

Abstract

Immunohistochemistry (IHC) combined with fluorescence microscopy provides an important and widely used tool for researchers and pathologists to image multiple biomarkers in tissue specimens. However, multiplex IHC using standard fluorescence microscopy is generally limited to 3-5 different biomarkers, with hyperspectral or multispectral methods limited to 8. We report the development of a new technology based on novel photocleavable mass-tags (PC-MTs) for facile antibody labeling, which enables highly multiplexed IHC based on MALDI mass spectrometric imaging (MALDI-IHC). This approach significantly exceeds the multiplexity of both fluorescence- and previous cleavable mass-tag-based methods. Up to 12-plex MALDI-IHC was demonstrated on mouse brain, human tonsil, and breast cancer tissues specimens, reflecting the known molecular composition, anatomy, and pathology of the targeted biomarkers. Novel dual-labeled fluorescent PC-MT antibodies and label-free small-molecule mass spectrometric imaging greatly extend the capability of this new approach. MALDI-IHC shows promise for use in the fields of tissue pathology, tissue diagnostics, therapeutics, and precision medicine.

Keywords

MALDI

bead-arrays

immunofluorescence

immunohistochemistry

in situ hybridization

mass spectrometric imaging

mass spectrometry

mass-tags

matrix-assisted laser desorption/ionization

multiplexing

pathology

photocleavable

tissue diagnostics

MeSH terms

Animals

Biomarkers

Biomarkers, Tumor

Brain Chemistry

Breast Neoplasms

Female

Fluorescent Antibody Technique

Humans

Immunohistochemistry

In Situ Hybridization

Mice

Microspheres

Palatine Tonsil

Peptides

Photochemistry

Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Streptavidin

Ultraviolet Rays

Authors

Yagnik, Gargey

Liu, Ziying

Rothschild, Kenneth J

Lim, Mark J

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