2. Serial Femtosecond Crystallography (SFX): An Overview

X-ray crystallography is a very powerful tool to determine structures of biological macromolecules at the atomic and molecular level and thereby enables insights into their function. Unfortunately, irradiating biological samples with X-rays is an inherently damaging and unavoidable process in conventional X-ray crystallography. The unique properties of X-ray free electron lasers (FELs), with pulse duration in the femtosecond range, allow data collection at time scales shorter than, or equivalent to, the time scales of the X-ray induced radiation damage pathways, offering a plausible way to diminish the ill effects of conventional radiation damage in biological structure determination. However, the high intensities of the X-ray FEL beam necessitated the development of novel techniques for sample preparation, characterization, introduction, data collection, and analysis. Serial femtosecond crystallography (SFX) represents a set of techniques developed to enable X-ray crystallography experiments at X-ray FELs, which encompasses multiple developments in sample introduction and data collection. This chapter summarizes the early experiments that demonstrated the SFX methods along with more recent developments and accomplishments that will be discussed in more detail in the following chapters of this book.