If you can't see it... just make it bigger: The development of Expansion Microscopy

For hundreds of years, scientists have been developing ever better methods of microscopy for visualizing the molecular world.

Turns out this has been a massive waste of time. Why bother making your microscope better when you can just make your sample bigger?

That's the idea behind Expansion Microscopy (ExM), which was developed by Ed Boyden's lab at MIT. ExM uses a polyelectrolyte polymer to physically anchor, and then expand the sample, causing minimal disruption of structure, while achieving superresolution with diffraction limited microscopes. In some cases ExM could achieve higher resolution with a confocal system than was possible with a superresolution approach like Structured Illumination Microscopy.

While the Boyden group’s 2015 paper describing ExM isn’t so much of an experiment, I think this lands squarely in the category of “I wish I’d thought of that,” and in my opinion is one of the great experiments of microscopy.  

• Chen F, Tillberg P, Boyden E. 2015. Expansion Microscopy. Science.

Supplements:
New York Times -- Expansion Microscopy Stretches Limits of Conventional Microscopes

Ed Boyden's Ted Talk -- A New Way to Study the Brain's Invisible Secrets