High contrast at low dose using a single, defocussed transmission electron micrograph

For many soft-matter specimens, transmission electron microscopists face the double-bind of low contrast images, due to weakly-scattering specimens, alongside severe limits on the electron dose that can be used before the specimen is damaged by the electron beam. The combination of these effects causes the resultant micrographs to have very low signal-to-noise. It is well known that varying the defocus aberration can enhance image contrast in electron microscopy. For single-material objects where the variation of absorption and phase contrast are functions of one another, since both are governed by the variation in thickness profile, we show that the thickness profile can be reconstructed at very low dose. The algorithm, first established in X-ray imaging, requires some a priori information but only a single defocussed image of the region of interest, making it more dose efficient than either a conventional transport-of-intensity phase reconstruction (which would require two images and tends to amplify noise), or an absorption-contrast analysis of a single in-focus image recorded at the same electron dose (which does not benefit from the significant signal-to-noise enhancement of the present algorithm). These findings are presented through both simulations and experimental data.