Pre-print · 2025
High-background X-ray single particle imaging enabled by holographic enhancement with 2D crystals
Authors
Abhishek Mall, Zhou Shen, Kartik Ayyer
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 XFELs remain limited due to strong background scattering. We computationally explore a modified SPI technique based on holographic enhancement using a strongly scattering 2D crystal lattice placed near the object. The Bragg peaks from the crystal enable structure retrieval even at background levels ≳10× stronger than the object signal. This method could enable SPI at synchrotrons, supports practical fixed-target sample delivery, and unlocks high-resolution imaging under near-native conditions. Numerical simulations with a custom reconstruction algorithm demonstrate enhanced achievable resolution and broadened accessibility to SPI.