ABSTRACT
Historically, the developments in electron microscopy and sample preparation have been closely linked to the structure determination of viral nanoparticles. This is partly due to the high availability of some of these viral nanoparticles and to their high symmetry. Tobacco mosaic virus (TMV) was
one of the earliest objects that have been imaged with the electron microscope (Kausche et al. 1939). However, sample preparation methods were still crude and relied on drying of the virus from a low-salt buffer. The drying conditions led to bending and distortions of the virus. Furthermore, the lack of contrast made it difcult to recognize features.
