title: Single-molecule imaging with longer X-ray laser pulses.
abstract: During the last five years, serial femtosecond crystallography using X-ray laser pulses has been developed into a powerful technique for determining the atomic structures of protein molecules from micrometre- and sub-micrometre-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 were 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, but can succeed for pulses 50-100 fs in duration. It is shown 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 the average structure separately to the diffraction from statistical fluctuations of the structure due to damage ('damage noise'). The results suggest that sub-nanometre single-molecule imaging with 30-50 fs pulses, like those produced at currently operating facilities, should not yet be ruled out. The theory presented 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.
authors.affiliation: ARC Centre of Excellence for Advanced Molecular Imaging, School of Physics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Martin
authors.affiliation: ARC Centre of Excellence for Advanced Molecular Imaging, School of Physics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Justine K
authors.initials: JK
authors.lastname: Corso
authors.affiliation: Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20 Uppsala, Sweden ; Center for Free-Electron Laser Science, DESY, Notkestrasse 85, DE-22607 Hamburg, Germany.
authors.forename: Carl
authors.initials: C
authors.lastname: Caleman
authors.affiliation: Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20 Uppsala, Sweden ; Department of Cell and Molecular Biology, Uppsala University, Box 596, SE-751 24 Uppsala, Sweden.
authors.forename: Nicusor
authors.initials: N
authors.lastname: Timneanu
authors.affiliation: ARC Centre of Excellence for Advanced Molecular Imaging, School of Physics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Harry M
authors.initials: HM
authors.lastname: Quiney
keywords: XFELs; coherent diffractive imaging; radiation damage; single-molecule imaging; ‘self-gated’ pulses