Due to high spatial resolution (e.g. a few nanometres) in biological specimen, TEM allows direct observation of cellular compounds and organelles, cytoskeletal elements, single synaptic vesicles, ribosomes and even protein complexes.
TEM images of thin biological, frozen-hydrated specimens must be recorded with a substantial degree of defocus in order to generate adequate contrast at low spatial frequencies.
In tilt electron tomography, due to the strong interaction of the electron beam with the specimen, bright-field TEM imaging is mainly used in biological tomography but is in general inapplicable to the study of crystalline materials because the diffraction contrast and Fresnel fringes do not satisfy the projection requirement and can lead to serious artifacts in reconstructions. On the other hand, the HAADF (high-angle annular dark-field) STEM imaging offers an excellent alternative due to its Z-contrast.
To avoid electron beam damage on beam-sensitive biological materials, low electron doses are needed during TEM and STEM imaging, and elemental mapping (see page4412).