diffractionbeforedestruction

Diffraction-before-destruction is a principle in X-ray crystallography that uses ultrafast, intense X-ray pulses to collect diffraction data from a crystal before radiation damage destroys the sample. The concept became central with the advent of X-ray free-electron lasers (XFELs), which produce femtosecond-scale X-ray pulses in high flux, enabling a single exposure to capture a diffraction pattern from a microcrystal.

In practice, many microcrystals are delivered into the XFEL beam (via a liquid jet or fixed-target holder) and each crystal is exposed to a single femtosecond pulse. The duration is short enough that atomic motion is negligible during the pulse, so the diffraction pattern reflects the undistorted lattice. After the pulse the crystal is destroyed, necessitating a new crystal for the next pattern. Because the crystal orientation is unknown, diffraction patterns from large numbers of crystals must be collected and computationally indexed and merged to compose a full three-dimensional dataset. Phasing is achieved by standard approaches such as molecular replacement or experimental phasing, often aided by high-quality models or anomalous signals.

Applications include determination of structures from radiation-sensitive proteins, nanocrystals, membrane proteins, and virus particles, often at room temperature and with time-resolved experiments to watch dynamics on femtosecond to picosecond scales. Limitations include the need for abundant microcrystals, complex data processing, and reliance on XFEL facilities.

Related topics include X-ray free-electron lasers, serial femtosecond crystallography, and serial crystallography.