Low-dose cryo electron ptychography via non-convex Bayesian optimization

TL;DR

This paper introduces a non-convex Bayesian optimization method for cryo-electron ptychography, significantly reducing radiation dose requirements and enabling high-resolution imaging of biological samples at cryogenic temperatures.

Contribution

The authors develop a novel non-convex Bayesian optimization approach that lowers the dose needed for successful cryo-electron ptychography by two orders of magnitude.

Findings

Achieved 7.9 Å resolution at 20 e⁻/Ų dose in simulated data

Demonstrated 4 Å resolution with 15 low-dose datasets

Showed potential of cryo-electron ptychography as an alternative to Zernike phase-contrast microscopy

Abstract

Electron ptychography has seen a recent surge of interest for phase sensitive imaging at atomic or near-atomic resolution. However, applications are so far mainly limited to radiation-hard samples because the required doses are too high for imaging biological samples at high resolution. We propose the use of non-convex, Bayesian optimization to overcome this problem and reduce the dose required for successful reconstruction by two orders of magnitude compared to previous experiments. We suggest to use this method for imaging single biological macromolecules at cryogenic temperatures and demonstrate 2D single-particle reconstructions from simulated data with a resolution of 7.9 \AA$\,$ at a dose of 20 $e^- / \AA^2$. When averaging over only 15 low-dose datasets, a resolution of 4 \AA$\,$ is possible for large macromolecular complexes. With its independence from microscope transfer function, direct recovery of phase contrast and better scaling of signal-to-noise ratio, cryo-electron ptychography may become a promising alternative to Zernike phase-contrast microscopy.