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Updated: Jun 13, 2026

Universal Molecular Retention with 11-Fold Expansion Microscopy
Published on: October 6, 2023
Thousandfold Expansion Microscopy
Helena Hu1, Donatus Krah2, Antonios Ntolkeras2
1Department of Biological Engineering, MIT, Cambridge, MA 02139.
Thousandfold expansion microscopy (1000ExM) images individual protein residues by anchoring and expanding them. This novel technique achieves sub-nanometer precision, enabling detailed protein visualization.
Area of Science:
- Biochemistry
- Microscopy
- Materials Science
Background:
- Proteins are essential biological macromolecules composed of amino acid residues.
- Current imaging techniques face limitations in resolving individual amino acid residues within proteins.
Purpose of the Study:
- To develop a novel microscopy technique for visualizing individual protein residues.
- To achieve sub-nanometer precision in imaging protein structures.
Main Methods:
- Anchoring protein side chains to a swellable polymer.
- Cleaving backbone amide bonds to separate residues.
- Utilizing a four-network interpenetrating hydrogel architecture for successive expansion (1000ExM).
Main Results:
- Achieved successive expansion up to >1000-fold (one billion-fold in volume).
- Maintained protein and peptide structures across expansion factors.
- Demonstrated resolution of adjacent amino acid residues, achieving sub-nanometer precision.
Conclusions:
- 1000ExM enables visualization of individual protein residues with unprecedented precision.
- This technique offers potential for wide application in protein visualization and identification.
- 1000ExM may be applicable in intact cells and tissues.
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