The idea of measuring molecular mass using an electron microscope was first proposed by Zeitler and Bahr (Zeitler & Bahr 1962). The principle is based on the approximately linear relationship between the fraction of incident electrons scattered by a specimen and its molecular mass. Although the basic theory was developed at this time, experimental measurements were limited to rather large structures until the development of the field emission gun and its use in the high-resolution Scanning Transmission Electron Microscope (STEM).Quantitative electron microscopic techniques allow the following types of mass measurements:
- mass-per-particle of globular structures (e.g., single macromolecules, globular assemblies);
- mass-per-length of filamentous structures (e.g., intermediate filaments, tobacco mosaic virus);
- mass-per-area of sheet-like structures (e.g., protein S-layers).
- Wall, J.S., Isaacson, M., Langmore, J.P.: The collection of scattered electrons in dark field electron microscopy. Optik39 (1974), 359-374.
- Zeitler, E., Bahr, G.F.: A photometric procedure for weight determination of submicroscopic particles quantitative electron microscopy. J. Appl. Phys.33 (1962), 847-853.