Holography and Coherent Diffraction with Low-Energy Electrons: A Route towards Structural Biology at the Single Molecule Level

TL;DR

This paper introduces a novel low-energy electron holography and coherent diffraction method enabling high-resolution, non-destructive, single-molecule imaging, potentially revolutionizing structural biology by bypassing ensemble averaging.

Contribution

The work demonstrates a lens-less imaging technique combining holography and diffraction that achieves atomic resolution at the single-molecule level without phase retrieval.

Findings

Achieved 2 Angstrom resolution in graphene imaging.

Successfully imaged 660,000 unit cells from a single dataset.

Potential to distinguish protein conformations at atomic resolution.

Abstract

The current state of the art in structural biology is led by NMR, X-ray crystallography and TEM investigations. These powerful tools however all rely on averaging over a large ensemble of molecules. Here, we present an alternative concept aiming at structural analysis at the single molecule level. We show that by combining electron holography and coherent diffraction imaging estimations concerning the phase of the scattered wave become needless as the phase information is extracted from the data directly and unambiguously. Performed with low-energy electrons the resolution of this lens-less microscope is just limited by the De Broglie wavelength of the electron wave and the numerical aperture, given by detector geometry. In imaging freestanding graphene, a resolution of 2 Angstrom has been achieved revealing the 660.000 unit cells of the graphene sheet from one data set at once. Applied to individual biomolecules the method allows for non-destructive imaging and imports the potential to distinguish between different conformations of proteins with atomic resolution.