Sample Delivery Techniques for Serial Crystallography

In serial femtosecond crystallography (SFX), protein microcrystals and nanocrystals are introduced into the focus of an X-ray free electron laser (FEL) beam ideally one-by-one in a serial fashion. The high photon density in each pulse is the double-edged sword that necessitates the serial nature of the experiments. The high photon count focused spatially and temporally leads to a diffraction-before-destruction snapshot, but this single snapshot is not enough for a high-resolution three-dimensional structural reconstruction. To recover the structure, more snapshots are required to sample all of reciprocal space from randomly oriented crystal diffraction, and in practice, some redundancy is necessary in these measurements. This chapter explores the different sample delivery techniques developed over the years to help enable serial crystallography experiments.