Ultra-expansion microscopy
The ultra-expansion microscopy method refines the original protocol from 2015, ensuring more isotropic sample preservation and simplified yet stronger labeling, thus becoming an art form that matches the resolution of electron microscopy. In principle, the sample is physically magnified in a swellable hydrogel before microscopic examination. By demonstrating the undistorted chirality and length of microtubules assembling the core centrosomal structure (centrioles) of sub-diffraction size, we provided direct evidence of the technique's precision. The resolution reached new heights due to subsequent sub-optimizations, combining it with super-resolution microscopy. This technique later helped to visualize plant nuclei, human cells, and the Trypanosoma parasite.
To expand a sample, first, place the fixed specimen on a flat surface and embed it within a liquid hydrogel solution. After letting the gel solidify, disrupt the chemical bonds between parts of the sample through denaturation, and then place the entire gel-sample hybrid in pure water to expand it. This process physically introduces gaps between the sample's individual components, effectively allowing you to see diffraction-limited details with an ordinary wide-field microscope.