Transmission electron microscopes (TEMs) are powerful analytical tools for investigating very small structures. TEMs can show all the structures of a tissue and compartmentalisation of mutually exclusive regions of cells by membrane-enclosed organelles.
Transmitting a beam of electrons through a specimen captures very fine details thousands of times smaller than those seen in a light microscope. This allows the molecular machinery of cells from atomic details to the cellular context and beyond to be studied and understood. This complements light microscopy where fluorescent tags display proteins confined to compartments in living cells, but give no glimpse of the underlying ultrastructure.
Electron microscopes operate at vacuum so biological samples must be prepared in a specific way. This can involve negative staining of viruses and proteins, chemical fixation, dehydration, embedding and cutting (~70nm) thin sections of tissue. In each case, electron dense heavy-metal stains provide contrast.
Although well established in biological research, specimen preparation often introduces processing artefacts (perturbations to structure), so when possible cryo electron microscopy techniques are preferable.
