The high sensitivity of electron energy-loss spectroscopy (EELS) for detecting light elements at the nanoscale makes it a valuable technique for application to biological systems. In particular, EELS provides quantitative information about elemental distributions within subcellular compartments, specific atoms bound to individual macromolecular assemblies, and the composition of bionanoparticles. EELS data can be acquired either in the fixed beam energy-filtered transmission electron microscope (EFTEM) or in the scanning transmission electron microscope, and recent progress in the development of both approaches has greatly expanded the range of applications for EELS analysis. Near single atom sensitivity is now achievable for certain elements bound to isolated macromolecules, and it becomes possible to obtain three-dimensional compositional distributions from sectioned cells through EFTEM tomography.

Parallel-detection electron energy loss spectroscopy (EELS) in the scanning transmission electron microscope provides a very sensitive means of detecting specific elements in biological systems. By analyzing EELS spectrum-image data recorded from rapidly-frozen and cryosectioned tissue it is possible to map quantitatively the distribution of the biologically important element, calcium, which is typically present at concentrations of only a few parts per million in cellular structures some tens of nanometers in diameter. A significant improvement (factor of four) in calcium detectability has been demonstrated for EELS compared with energy-dispersive x-ray spectroscopy. The spectrum-imaging technique has also been applied to map water distributions in hydrated biological specimens by utilizing the valence electron excitations.