A guide to sample delivery systems for serial crystallography

Crystallography has made a notable contribution to our knowledge of structural biology. For traditional crystallography experiments, the growth of crystals with large size and high quality is crucial, and it remains one of the bottlenecks. In recent years, the successful application of serial femtosecond crystallography (SFX) provides a new choice when only numerous microcrystals can be obtained. The intense pulsed radiation of X-ray free-electron lasers (XFELs) enables the data collection of small-sized crystals, making the size of crystals no longer a limiting factor. The ultrafast pulses of XFELs can achieve ‘diffraction before destruction’, which effectively avoids radiation damage and realizes diffraction near physiological temperatures. More recently, the SFX has been expanded to serial crystallography (SX) that can additionally employ synchrotron radiation as the light source. In addition to the traditional ones, these techniques provide complementary opportunities for structural determination. The development of SX experiments strongly relies on the advancement of hardware including the sample delivery system, the X-ray source, and the X-ray detector. Here, in this review, we categorize the existing sample delivery systems, summarize their progress, and propose their future prospectives.