Single molecule imaging with longer x-ray laser pulses

TL;DR

This paper demonstrates that damage effects in single molecule x-ray diffraction can be mitigated with longer pulses, enabling sub-nanometer imaging with current laser facilities by leveraging a self-gating effect similar to that in crystallography.

Contribution

It extends the concept of the self-gating pulse effect from crystallography to single molecule imaging, showing damage effects can be managed with longer pulses.

Findings

Damage terminates diffraction before pulse ends, similar to crystallography.

Sub-nanometer single molecule imaging with 30-50 fs pulses is feasible.

The theory enables new experiments to measure damage impacts.

Abstract

During the last five years, serial femtosecond crystallography using x-ray laser pulses has developed into a powerful technique for determining the atomic structures of protein molecules from micrometer and sub-micrometer sized crystals. One of the key reasons for this success is the "self-gating" pulse effect, whereby the x-ray laser pulses do not need to outrun all radiation damage processes. Instead, x-ray induced damage terminates the Bragg diffraction prior to the pulse completing its passage through the sample, as if the Bragg diffraction was generated by a shorter pulse of equal intensity. As a result, serial femtosecond crystallography does not need to be performed with pulses as short as 5--10 fs, as once thought, but can succeed for pulses 50--100 fs in duration. We show here that a similar gating effect applies to single molecule diffraction with respect to spatially uncorrelated damage processes like ionization and ion diffusion. The effect is clearly seen in calculations of the diffraction contrast, by calculating the diffraction of average structure separately to the diffraction from statistical fluctuations of the structure due to damage ("damage noise"). Our results suggest that sub-nanometer single molecule imaging with 30--50 fs pulses, like those produced at currently operating facilities, should not yet be ruled out. The theory we present opens up new experimental avenues to measure the impact of damage on single particle diffraction, which is needed to test damage models and to identify optimal imaging conditions.