Two important breakthroughs recent years have been lensless imaging (based on iterative solutions of the phase problem for non-periodic samples), and the ability to out-run radiation damage by using femtosecond pulses of illumination. (By packing an arbitrarily large number of photons, for example, into a sufficiently brief pulse, one breaks the nexus between sample size, dose, and resolution, allowing diffraction limited, damage free, atomic-resolution imaging, in principle. Sources based on lasers now approach this). I’ll discuss how these discoveries may be combined toward the goal of recording movies of molecular machines at work, with high time and spatial resolution. For pulsed electron-beams, I’ll discuss prospects for outrunning damage using an MeV diffraction camera, and a fast mode of image formation which can provide high resolution despite the use of the large incoherent photocathode needed to provide many electrons in a pulse brief pulse. I’ll then review our work using the hard X-ray laser at SLAC within our BioXFEL 6-campus NSF consortium in the USA (http://www.bioxfel.org), aimed at the application of X-ray lasers (XFELs) to Biology. Molecular movies have been obtained for light-sensitive proteins with 500 fs time resolution and near-atomic spatial resolution, both using protein nanocrystals (using the Bragg Boost), and molecules in solution.
I’ll discuss work in my lab on methods for delivering a stream of biological samples across the XFEL beam (each destroyed, after producing useful elastic scattering), and on the diffraction physics needed to analyse this new data. Other projects include our mixing jet (for imaging slower chemical reactions), split-and-delay “2-color” schemes, and the use of attosecond pulses for Laue mode diffraction, where the bandlimit for such brief pulses provides the broad energy spectrum needed for full reflections in each destructive-readout shot. See Google Scholar for references and the many collaborators who I thank.