Cryo compatible sample grids having multi-modal cryo-EM compatible GUIDs, according to the present disclosure include an outer support structure that defines a region of the grid for holding one or more samples, and a plurality of inner support structures that define a plurality of apertures that are each configured to hold a sample. Cryo compatible sample grids further include a first identifier located on the outer support structure, and a second identifier located within the region of the grid for holding the one or more samples. The first identifier is readable with an optical detector, while the second identifier is readable with an electron detector (e.g., within an electron microscope). Specifically, the second identifier is readable with an electron detector when one or more teeth and/or holes that comprise the second identifier are filled with ice from a vitrification process.
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