Annular dark field transmission electron microscopy for protein structure determination

Recently annular dark field (ADF) transmission electron microscopy (TEM) has been advocated as a means of recording images of biological specimens with better signal to noise ratio (SNR) than regular bright field images. I investigate whether and how such images could be used to determine the three-dimensional structure of proteins given that an ADF aperture with a suitable pass-band can be manufactured and used in practice. I develop an approximate theory of ADF-TEM image formation for weak amplitude and phase objects and test this theory using computer simulations. I also test whether these simulated images can be used to calculate a three-dimensional model of the protein using standard software and discuss problems and possible ways to overcome these. - Highlights: • I present theory and simulations for imaging proteins using annular dark field transmission electron microscopy and investigate its suitability for 3D-reconstruction. • I show that the images are approximately proportional to the square of the projected electrostatic potential within a given passband ). • 3D-reconstructions show errors in the interior of the molecule. More accurate maps might be calculated by reconstruction algorithms that take into account non-linear image formation.