High-background X-ray single particle imaging enabled by holographic enhancement with 2D crystals

TL;DR

This paper proposes a holographic enhancement method using 2D crystal lattices to improve X-ray single particle imaging, enabling higher resolution and greater accessibility at more common sources like synchrotrons.

Contribution

It introduces a novel computational approach that leverages crystal Bragg peaks for structure retrieval amidst high background noise, expanding the practical application of SPI.

Findings

Bragg peaks enable structure recovery at background levels up to 10^5 times the object signal

Simulation results show potential for higher resolution imaging

Method supports use at more accessible synchrotron sources

Abstract

X-ray single particle imaging (SPI) has offered the potential to visualize structures of biomolecules at near-atomic resolution. However, state-of-the-art structures at X-ray free electron lasers (XFELs) are limited to moderate resolution, primarily due to background scattering. We computationally explore a modified SPI technique based on holographic enhancement from a strongly scattering 2D crystal lattice placed near the object. The Bragg peaks from the crystal enable structure retrieval even for background levels up to 10$^{5}$ times higher than the object signal. This method could enable SPI at more widely accessible synchrotron sources, where even detection of objects before radiation damage is nearly impossible currently, supports practical fixed-target sample delivery, and enables high-resolution imaging under near-native conditions. Numerical simulations with a custom reconstruction algorithm to recover the latent parameters show the potential to improve the achievable resolution while also expanding the accessibility to the technique.