Expansion microscopy uses a polymer to physically enlarge a sample evenly in 3D to allow nanoscale precision imaging of structures with ordinary widefield or confocal microscopes, rather than superresolution microscopy which can be damaging to the sample. 

The methodology is to:  

  1. Fluorescently label the specimen 

  2. Anchor key labels or biomolecules to the swellable polymer that is distributed evenly throughout specimen  

  3. Break down structures in the sample that could distort the structure in the expansion process  

  4. Expand the resultant tissue-material composites. 

Wassie, A.T. et al. 2019 






Expansion Microscopy Explained 

Expansion microscopy resource page. 

How can I use this technique? 

This tissue preparation technique results in a 4.5× linear expansion, therefore a microscope with a diffraction limit of ~300 nm would be able to attain an effective resolution of ~300 nm/4.5 ≈ 70 nm.  

It is also possible to expand specimens twice in series, thus enabling an ~4.5 × 4.5 ≈ 20× increase in linear dimension, resulting in an effective resolution of 300/20 ≈ 15 nm 

Sven Truckenbrodt (IST Austria): X10 Expansion Microscopy 

A 10x linear expansion technique has also been achieved.