Immuno‐Desorption Electrospray Ionization Mass Spectrometry Imaging Identifies Functional Macromolecules by Using Microdroplet‐Cleavable Mass Tags

We present immunoassay‐based desorption electrospray ionization mass spectrometry imaging (immuno‐DESI‐MSI) to visualize functional macromolecules such as drug targets and cascade signaling factors. A set of boronic acid mass tags (BMTs) were synthesized to label antibodies as MSI probes. The boroni...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2023-02, Vol.62 (9), p.e202216969-n/a
Main Authors: Song, Xiaowei, Zang, Qingce, Li, Chao, Zhou, Tianhao, Zare, Richard N.
Format: Article
Language:English
Subjects:
Ammonium
Antibodies
Boron
D-Galactosamine
Desorption
Desorption Electrospray Ionization
Diagnostic Imaging
Electrospraying
Fluorescence
Imaging
Immunoassay
Ionization
Macromolecules
Mass spectrometry
Mass Spectrometry Imaging
Mass spectroscopy
Mass Tag
Microdroplets
Spectrometry, Mass, Electrospray Ionization - methods
Tags
Therapeutic targets
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Summary:We present immunoassay‐based desorption electrospray ionization mass spectrometry imaging (immuno‐DESI‐MSI) to visualize functional macromolecules such as drug targets and cascade signaling factors. A set of boronic acid mass tags (BMTs) were synthesized to label antibodies as MSI probes. The boronic ester bond is employed to cross‐link the BMT with the galactosamine‐modified antibody. The BMT can be released from its tethered antibody by ultrafast cleavage of the boronic ester bond caused by the acidic condition of sprayed DESI microdroplets containing water. The fluorescent moiety enables the BMT to work in both optical and MS imaging modes. The positively charged quaternary ammonium group enhances the ionization efficiency. The introduction of the boron element also makes mass tags readily identified because of its unique isotope pattern. Immuno‐DESI‐MSI provides an appealing strategy to spatially map macromolecules beyond what can be observed by conventional DESI‐MSI, provided antibodies are available to the targeted molecules of interest. Water‐microdroplet‐cleavable, bifunctional boronate mass tags are introduced to conduct cell‐resolved immunofluorescence imaging followed by multiplex immuno‐desorption electrospray ionization mass spectrometry imaging.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202216969