Quantitative analysis with electron energy-loss: spectroscopic imaging and its application in pathology

After the invention of the transmission electron microscope (TEM) in 1931 by Ruska and Knoll, it took about 20 years to develop the inslmment into a tool for ultrastructural research. In material science this led to the ability to visualize and investigate atomic arrangements through the imaging of columns of atoms in a lattice or by electron diffraction. In biology the instrument enabled the visualization of cell structures at an unsurpassed level of detail. New cell structures, cells and organisms were depicted and more knowledge was gained about the complex ultrastructural morphology of the cell. Novel preparation procedures for fixation, cytochemical staining and labelling, embedding and the llse of ultramicrotomy and cryo-techniques increased the investigative capabilities of the TEM in the direction of cell functioning. In physics, right from the beginning, it was recognized that the interaction of electrons irradiating a specimen can be used not only for visualization but also gives the opportunity to investigate the chemical nature of the irradiated matter. This opened the way to the analytical use of the TEM and many instruments were subsequently equipped with highly specialized detectors for each of the analytical possibilities. In this way true microanalytical laboratories were created. Two main types of TEMs have been developed: the scanning transmission electron microscope (STEM) and the conventional transmission electron microscope (CTEM).