Not many samples, many copies of the protein in what is often a single crystal (although if it's easily damaged, you might to use multiple crystals and combine the data post-processing). EM is actually very destructive, so they have to take thousands of micrographs of different individual molecules, and average them together.

Oh, okay, thanks! I've edited my comment to be hopefully less wrong.

So it's like the x-ray version, just a different approach / energy scale? Or is that comparison ... doesn't make sense?

Both techniques give you the average electron density over thousands to billions of molecules. The difference is in what kind of data you actually collect, and how you process and combine the data to get that averaged map:

- In X-ray crystallography, you're collecting the amplitudes of the Fourier transform of the electron density in the repeating unit of the crystal. The fact that it's a well-ordered (usually) crystal effectively "amplifies" the FT, and you get a series of images like this (from one orientation of the crystal): https://cdn.britannica.com/02/147302-050-3F732246/X-ray-diff...

- In EM, you're collecting direct images of particles randomly distributed on a grid, but they're 2D and individually very noisy, like this: https://www.pnas.org/content/pnas/110/45/18037/F3.large.jpg?...

In either case, there's a lot of complex math that goes into reconstructing the electron density - but the end result, the electron density map, is very similar (aside from the absence of crystal packing interactions in the EM map).