Image contrast of biological macromolecules in electron microscopy under accelerated voltage

Image contrast in the tilted beam mode of dark field (DF) imaging with a conventional transmission electron microscope has been estimated theoretically for two well-known biological macromolecules viz. lambda-phage DNA and BSA precursor protein. The DF contrast for electron accelerating voltage 0.1 to 3.0 MV has been compared with the corresponding bright field (BF) contrast. The DF contrast is seen to be so overwhelmingly greater than the BF contrast, for a wide range of accelerating voltage (phi) and aperture (alpha), that even an unstained bio-macromolecule should become visible under high voltage DF imaging.