Compositional imaging in biology: limits and potential

Abstract

Compositional imaging of cells and organelles in physiological and pathological states is a major challenge and opportunity for structural biology, but its potential for revealing new and significant biological information depends on the attainable sensitivity and spatial resolution. Since most biological materials consist of “trace concentrations” of elements embedded in an organic matrix composed of carbon, nitrogen, and oxygen, the minimal detectable concentration, rather than minimal detectable mass, is often the more important criterion of sensitivity. The past two decades have seen significant progress in the application of analytical electron microscopy [AEM] to biology and, after a brief standstill, the next decade offers further significant advances.The preparatory method suitable for “high resolution” analysis of most biological materials is now well-established: rapid freezing, followed by cryoultramicrotomy and freeze drying to produce ultra thin specimens. Until recently, electron probe x-ray microanalysis and, related to it, x-ray mapping has been the most successful analytical method.