Structure determination through correlated fluctuations in x-ray scattering

It was suggested more than three decades ago that the three-dimensional structure of one particle may be determined using the simultaneous x-ray scattering from many randomly oriented copies ab initio, without modelling of a priori information. This may be possible, provided sufficiently brief and intense x-ray pulses that can 'outrun' the effects of radiation damage and simultaneously produce significant signal within 'snapshot' diffraction patterns. Because the ensemble of particles is static throughout the snapshot exposure, solution scattering patterns contain angular intensity fluctuations and thus differ from conventional isotropic scattering patterns. X-ray free-electron lasers may be able to provide the x-ray source properties that are required to make such experiments feasible. In this tutorial we discuss how structures might be determined through correlated x-ray scattering measurements, with an emphasis on dilute suspensions of identical bioparticles.