Expansion Microscopy (ExM) is a sample preparation tool for biological samples that allows investigators to identify small structures by expanding them using a polymer system. The premise is to introduce a polymer network into cellular or tissue samples, and then physically expand that polymer network using chemical reactions to increase the size of the biological structures. Among other benefits, this allows those small structures to be imaged with a wider range of microscopy techniques. It was first proposed in a 2015 article by Fei Chen, Paul W. Tillberg, and Edward Boyden.
Traditional light microscopy has limits of resolution that prevent it from reliably distinguishing small structures that are important to biological function, and must instead be imaged by a lower-resolution technique, such as electron microscopy. For example, synaptic vesicles are 40-50 nanometers in diameter, which is below the commonly quoted resolution limit of 200 nanometers for light microscopy. Expansion microscopy solves this problem by expanding the underlying tissue sample. One key advantage of samples prepared using expansion microscopy and light microscopy over conventional electron microscopy is that it also allows for investigators to stain for and visualize particular molecules in the sample, such as proteins or RNA to identify their density and distribution in relation to the biological structures of interest.