Towards single atom analysis of biological structures

Mapping single atoms in biological structures is now becoming within the re ach of analytical electron microscopy. Electron energy-loss spectroscopy (E ELS) in the field-emission scanning transmission electron microscope (STEM) provides a particularly high sensitivity for detecting the biologically im portant element, phosphorus. Imaging can be performed at low dose with dark -field STEM prior to analysis at high dose, so that structures of macromole cular assemblies can be correlated with the numbers of specific atoms that they contain. Measurements confirm theoretical predictions that single atom detection requires a nanometer-sized probe. Although phosphorus atoms may have moved several nanometers from their original positions by beam-induced structural degradation at the high required dose of similar to 10(9) e/nm( 2), damaged molecules are nevertheless stable enough to be analyzed at 1 or 2 nm resolution. Such analyses can only be achieved by means of spectrum-i maging with correction for specimen drift. Optimal strategies for mapping s mall numbers of phosphorus atoms have been investigated using well-characte rized specimens of DNA plasmids and tobacco mosaic virus. Published by Else vier Science B.V.