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Related Concept Videos

MALDI-TOF Mass Spectrometry01:19

MALDI-TOF Mass Spectrometry

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Mass spectrometry is a powerful characterization technique that can identify and separate a wide variety of compounds ranging from chemical to biological entities, based on their mass-to-charge ratio (m/z). The instruments that allow this detection, known as mass spectrometers, have three components: an ion source, a mass analyzer, and a detector. These spectrometers differ based on the nature of their ion source and analyzers.Matrix-assisted laser desorption ionization (MALDI) is a commonly...
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Multimodal Study of Murine Cardiovascular Remodeling: Four-Dimensional Ultrasound and Mass Spectrometry Imaging
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Spatial Multiomics Combining Lipids and Gene Expression Using MALDI ISH MSI.

Kyle A Vanderschoot1, Jacob P Padilla1, Kelli A Steineman1

  • 1Department of Chemistry, University of California, Davis, Davis, California 95616-5270, United States.

Analytical Chemistry
|March 19, 2026
PubMed
Summary
This summary is machine-generated.

Researchers developed a novel method combining in situ hybridization with mass spectrometry imaging for spatial multiomic analysis. This technique allows for simultaneous detection of gene expression and lipidomic data from the same tissue section, offering a scalable alternative for molecular studies.

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • Neuroscience

Background:

  • Existing spatial gene expression methods are limited by cost, time, and sampling area.
  • Matrix-assisted laser desorption/ionization in situ hybridization (MALDI ISH) mass spectrometry imaging (MSI) offers potential for spatial multiomics.

Purpose of the Study:

  • To develop a flexible and modular platform for spatial multiomic analysis by combining in situ hybridization with mass spectrometry imaging.
  • To enable serial detection of both gene expression and lipidomic data from the same tissue section.

Main Methods:

  • Synthesized a novel copper-catalyzed azide-alkyne cycloaddition (CuAAC) o-nitrobenzylic azide linker for conjugating DNA probes to peptide mass tags.
  • Utilized photocleavable linker for separating hybridized nucleic acid probes from peptide mass tags after hybridization.
  • Developed 33 unique photocleavable mRNA probes for multiplexed detection.

Main Results:

  • Successfully validated 12 distinct gene expression patterns in murine brain sections using the developed platform.
  • Demonstrated codetection of native RNA and lipidomic signals from the same tissue section.
  • Showcased the scalability of the platform for potential expanded multiplexing.

Conclusions:

  • The developed MALDI ISH-MSI approach provides a powerful alternative for spatial multiomic analysis.
  • This method offers new insights into transcriptome-metabolome interactions across different disease models.
  • The platform is broadly applicable and supports advanced molecular investigations.