## 1 Structural Biology at XFEL Sources
### The European XFEL (EuXFEL)  
The EuXFEL is the world's first MHz-pulse-rate hard XFEL, consisting of a 1700 m supercooled linear accelerator (LINAC) and generating up to 17.5 GeV electron bunches. The electron bunches emit photons when passed through an undulator, which is finely tuned to control the photon emission [17; 42]. The EuXFEL currently operates three undulators to serve six different instruments. The focus of this review is limited to one--the Single Particles, Clusters, and Biomolecules/Serial Femtosecond Crystallography (SPB/SFX) instrument, Figure 2--which addresses the field of XFEL structural biology. The SPB/SFX instrument is downstream from the so-called SASE1 undulator, which can produce photons of tunable energies in a range broader than the SPB/SFX instrument's operating range of 5-16 keV (and perhaps down to 3 keV with further commissioning and certain limitations). The machine is designed to produce X-ray pulses at a peak brilliance of \(5\times 10^{33}\) photons s\({}^{-1}\) mrad\({}^{-2}\)mm\({}^{-2}\) 0.1% bandwidth\({}^{-1}\)[13; 43; 44], approximately nine orders of magnitude brighter than that of current-generation synchrotron sources. Observations at the SASE1  
Figure 1: The Rayleigh breakup point can be seen where the stable liquid jet forms discrete droplets. The Rayleigh breakup length, or jet length, for a given solution is related to the jet diameter and the jet speed. Scale bar: 100 \(\upmu\)m. Figure originally published in Opt. Express [35].  
undulator have shown 4 mJ pulses at 6 keV photon energy, which correspond to about \(4\times 10^{12}\) photons per pulse. If we assume a pulse duration of 30 fs, we find that for an approximately 3 mm diameter beam near the instrument (about 900 m from the source), the brilliance is about \(2.25\times 10^{33}\) photons s\({}^{-1}\) mm\({}^{-2}\) mrad\({}^{-2}\) 0.1% bandwidth\({}^{-1}\). This peak brilliance is comparable with other XFEL sources, particularly LCLS [45], but the unique MHz repetition rate at the EuXFEL is currently not available at any other facility.  
MHz-repetition-rate hard X-ray sources provide unprecedented data collection rates and enable investigation of difficult and previously infeasible projects, such as time-resolved studies, so-called mixing experiments (where a protein crystal is mixed with a potential ligand, for example), or simply small crystal samples, within an experimentally feasible time frame [13; 44]. The MHz repetition rate can also be coupled with an optical laser pump-X-ray probe scheme with femtosecond time-delay resolution, as shown by [PERSON] et al. [46] Static samples, or samples which are not continuously refreshed, that do not recover to the ground state between MHz-rate pulses can also be studied by modifying the pulse pattern to account for the longer recovery period at the cost of the data collection rate.  
A novel, 1 Mpx Adaptive Gain Integrating Pixel Detector (AGIPD-1M) [47] has been developed to record individual scattering events. AGIPD-1M is capable of recording 4.5 MHz in three gain stages [48]. As each pixel is capable of selecting a gain stage appropriate for its level of signal--independently of surrounding pixels--low-intensity signals at higher resolution can be recorded, while simultaneously recording the low-resolution, high-intensity reflections.