Biological electron energy loss spectroscopy: the present and the future

The current state of electron loss spectroscopy (EELS) techniques and applications in biology is briefly reviewed. The field-emission scanning transmission electron microscope (STEM) equipped with a parallel detection spectrometer can localize and quantitate physiologically and bio- chemically relevant concentrations of many important elements in specimens prepared by suitable low-temperature techniques. The energy-filtering TEM is a complementary instrument, well suited for mapping locally high concentrations of elements over wider sample regions. With the STEM, nearly single-atom sensitivity can be achieved in the analysis of individual macromolecular assemblies although the spatial resolution is limited by radiation damage. Other STEM energy loss techniques that appear to be feasible include: low-dose elemental mapping of periodic structures; elemental labelling of organic and organometallic compounds in cells; thickness measurement of hydrated pro- teinb crystals, and measurement of water content in subcellular compartments.