Potential for biomolecular imaging with femtosecond X-ray pulses

Sample damage by X-rays and other radiation limits the resolution of struct ural studies on non-repetitive and non-reproducible structures such as indi vidual biomolecules or cells(1). Cooling can slow sample deterioration, but cannot eliminate damage-induced sample movement during the time needed for conventional measurements(1,2). Analyses of the dynamics of damage formati on(3-5) suggest that the conventional damage barrier (about 200 X-ray photo ns per Angstrom(2) with X-rays of 12 keV energy or 1 Angstrom wavelength 2) may be extended at very high dose rates and very short exposure times. Her e we have used computer simulations to investigate the structural informati on that can be recovered from the scattering of intense femtosecond X-ray p ulses by single protein molecules and small assemblies. Estimations of radi ation damage as a function of photon energy, pulse length, integrated pulse intensity and sample size show that experiments using very high X-ray dose rates and ultrashort exposures may provide useful structural information b efore radiation damage destroys the sample. We predict that such ultrashort , high-intensity X-ray pulses from free-electron lasers(6,7) that are curre ntly under development, in combination with container-free sample handling methods based on spraying techniques, will provide a new approach to struct ural determinations with X-rays.