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Updated: Jun 21, 2026
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Universal Molecular Retention with 11-Fold Expansion Microscopy
Published on: October 6, 2023
High-resolution molecular mapping by expansion-coupled label-free and multimodal imaging
Yat Ho Chan1, Maddison C Hibbard1, Ruixuan Gao2
1Department of Chemistry, University of Illinois Chicago, Chicago, IL, 60607, USA.
Current Opinion in Chemical Biology
|June 19, 2026
Summary
Expansion microscopy (ExM) physically enlarges biological samples to improve imaging resolution. Combining ExM with label-free imaging enables detailed molecular mapping at the subcellular level for advanced spatial biology.
Area of Science:
- Biophysics
- Microscopy
- Molecular Imaging
Background:
- Expansion microscopy (ExM) physically expands biological specimens to enhance effective spatial resolution.
- This technique circumvents the need for hardware modifications in existing imaging systems.
- Recent advances integrate ExM with label-free imaging modalities.
Purpose of the Study:
- To review the integration of expansion microscopy with label-free and multimodal imaging techniques.
- To discuss the advantages and challenges of this combined approach.
- To provide perspectives on future applications in spatial biology.
Main Methods:
- Physical expansion of biological specimens.
- Integration with label-free imaging modalities like stimulated Raman scattering microscopy and mass spectrometry imaging.
- Multimodal detection of chemical signatures.
Main Results:
- Achieved enhanced spatial resolution without altering imaging hardware.
- Enabled single-cell and subcellular molecular mapping.
- Facilitated label-free and multimodal detection of complex chemical signatures.
Conclusions:
- The coupling of expansion microscopy with label-free imaging is a powerful emerging approach.
- This combination offers significant advantages for high-resolution molecular mapping.
- Further development holds great promise for advancing spatial biology studies.
