The aim of electron probe microanalysis of biological systems is to
identify, localize, and quantify elements, mass, and water in cells and
tissues. The method is based on the idea that all electrons and photons
emerging from an electron beam irradiated specimen contain information
on its structure and composition. In particular, energy spectroscopy of
X-rays and electrons after interaction of the electron beam with the
specimen is used for this purpose. However, the application of this
method in biology and medicine has to overcome three specific
problems: 1. The principle constituent of most cell samples is water.
Since liquid water is not compatible with vacuum conditions in the
electron microscope, specimens have to be prepared without disturbing
the other components, in parti- cular diffusible ions (elements). 2.
Electron probe microanaly- sis provides physical data on either dry
specimens or fully hydrated, frozen specimens. This data usually has to
be con- verted into quantitative data meaningful to the cell biologist
or physiologist. 3. Cells and tissues are not static but dynamic
systems. Thus, for example, microanalysis of physiolo- gical processes
requires sampling techniques which are adapted to address specific
biological or medical questions. During recent years, remarkable
progress has been made to overcome these problems. Cryopreparation,
image analysis, and electron energy loss spectroscopy are key areas
which have solved some problems and offer promise for future
improvements.