Abstract: Methods and kits useful in expansion microscopy are described. In particular, the present disclosure relates to methods and kits for expanding or enlarging fixed samples of interest for microscopy by synthesizing a water-swellable compound within a fixed sample, which can be physically expanded, resulting in physical magnification of the sample. Furthermore, the methods and kits disclosed allow the use of fluorescent proteins expressed within the sample and/or the use of standard fluorophore-labeled secondary antibodies (referred to as conventional secondary antibodies) in expansion microscopy (ExM). Thus, conventional secondary antibodies and/or fluorescent proteins expressed within the sample can be used with conventional immunostaining for the optical imaging of a sample of interest with resolution better than the standard microscopy diffraction limit.