Imaging of objects by coherent diffraction of X-ray free-electron laser pulses

X-ray free-electron lasers produce pulses of coherent X-rays that are up to nine orders of magnitude higher in peak brightness than the brightest synchrotron sources. These pulses vaporize any object placed in the focused beam, yet are brief enough to diffract from the object before significant radiation damage occurs. This process of “diffraction before destruction” overcomes previous exposure and dose limitations when imaging biological structures, which allows atomic-resolution structures to be determined from macromolecules without the need for large, strongly diffracting crystals that are difficult or impossible to grow. The extreme pulse intensity has allowed protein crystal sizes to be shrunk down to dimensions of hundreds of nanometers, expanding the range of structures that can be studied, potentially increasing the rate at which new structures can be determined, and allowing the tracking of conformational dynamics down to femtosecond timescales. Efforts are ongoing to reduce this all the way to the single molecule, opening up possibilities for robust phasing procedures to acquire model-free structures directly from the measurements. The new science of coherent diffractive imaging would be well understood by the Braggs and Laue but makes use of recent theoretical insights, modern computational capabilities, and the laser-like X-ray sources of the twenty-first century.