Abstract: One aspect of the invention provides a method for preparing a biological sample. The method includes: exposing the biological sample to a photocrosslinkable substance adapted to bind to the biological sample, thereby forming a plurality of sample-photocrosslinkable-substance conjugates; embedding the sample in a hydrogel; and exposing the sample to light energy at a wavelength and intensity sufficient to cross-link the photocrosslinkable substance to the hydrogel.

Abstract: Methods and systems for physical expansion and imaging of biological samples are described herein. In one aspect of the disclosure, a method for preparing a biological sample for the purpose of generating images of its ultrastructure with an imaging instrument includes a) physically expanding the sample by at least a factor of two in at least one dimension; and b) bulk labeling a plurality of components of the sample with at least one reagent to introduce contrast.