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

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 show via numerical simulations that the dose required for successful reconstruction can be reduced by two orders of magnitude compared to previous experiments. As an important application 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 up to 5.4 Å at a dose of 20e −/Å2. When averaging over only 30 low-dose datasets, a 2D resolution around 3.5 Å is possible for macromolecular complexes even below 100 kDa. With its independence from the microscope transfer function, direct recovery of phase contrast, and better scaling of signal-to-noise ratio, low-dose cryo electron ptychography may become a promising alternative to Zernike phase-contrast microscopy.

A streaming multi-GPU implementation of image simulation algorithms for scanning transmission electron microscopy

“…Many largescale STEM experimental techniques are routinely validated using imaging or diffraction simulations. Examples include electron ptychography [6], 3D atomic reconstructions using dynamical scattering [7], high precision surface atom position measurements on catalytic particles [8], de-noising routines [9], phase contrast imaging with phase plates [10], new dynamical atomic contrast models [11], atomic electron tomography (AET) [12][13][14][15][16], and many others. The most commonly employed simulation algorithm for STEM simulation is the multislice algorithm introduced by Cowlie and Moodie [17].…”

Serial protein crystallography in an electron microscope

“…It is moreover not only limited to proteins but encompasses all nanocrystalline compounds, such as pharmaceuticals 47,48 or porous materials 23,49,50 . Augmenting parallel-beam crystallography with coherent scanning diffraction techniques such as convergent-beam diffraction or low-dose ptychography might be a viable way to obtain Bragg reflection phase information 51,52 . Finally, integrating the serial acquisition approach with emerging methods of in situ and time-resolved EM [53][54][55] may open up avenues for roomtemperature structures or structural dynamics studies on beamsensitive systems.…”

Serial protein crystallography in an electron microscope

“…It is moreover not only limited to proteins but encompasses all nanocrystalline compounds, such as pharmaceuticals 47,48 or porous materials 23,49,50 . Augmenting parallel-beam crystallography with coherent scanning diffraction techniques such as coherent nano-area diffraction, convergent-beam diffraction or low-dose ptychography might be a viable way to obtain Bragg reflection phase information 51,52 . Finally, integrating the serial acquisition approach with emerging methods of in-situ and time-resolved electron microscopy 53,54 may open up avenues for structural dynamics studies on beam-sensitive systems.…”