Electron probe microanalysis: its present, its future.

Electron probe microanalysis (EPM) is a method of elemental ultramicroanalysis based on the spectrometry of the characteristic X rays which are emitted when a target sample is excited by an electron beam. In the same sample many more elements (from carbon and up in the periodic table) in much smaller volumes (less than 1 micronm3 or 10(-15) liter) can be analyzed with EPM than with any other ultramicroanalytical method. Quantitation down to 10(-15) g is relatively easy. Any application of EPM in biology depends on the development of suitable methods for biological sample preparation. Liquid droplets of 10(-11)-liter volumes are routinely analyzed. Elemental content in isolated cells can be quantitated. The analysis of cellular, extracellular, and intercellular content in the same preparation is in sight: a general method for the analysis of diffusible elements in different compartments in tissue relies on the manipulation of frozen hydrated tissue near liquid nitrogen temperature. Localization in the same preparation of several organic compounds at high resolution will be possible by use of appropriate tags. All fields of microphysiology are likely to benefit from this new discipline.