The European X-ray Free Electron Laser is a research facility located close to Hamburg, offering X-ray pulses with ultra-high brilliance and femtosecond duration at megahertz repetition rates. The detection systems necessary to unlock the full scientific potential made possible by this machine poses considerable challenges both in terms of data volume and rate, as well as the interpretation of their recorded signal. To provide optimal data quality, expert and detector-specific knowledge not easily accessible to external facility users is essential, and its implementation must cope with the generated volumes. We therefore aim to perform these preparatory processing steps and offer users a dataset suitable for further analysis as the primary data product. This work describes the machinery and workflows providing this data to users in an automatic, configurable and reproducible manner, both online during the experiment, and offline for scientific analysis afterward on the way to publication.

The European XFEL is a megahertz repetition-rate facility producing extremely bright and coherent pulses of a few tens of femtoseconds duration. The amount of data generated in the context of user experiments can exceed hundreds of gigabits per second, resulting in tens of petabytes stored every year. These rates and volumes pose significant challenges both for facilities and users thereof. In fact, if unaddressed, extraction and interpretation of scientific content will be hindered, and investment and operational costs will quickly become unsustainable. In this article, we outline challenges and solutions in data reduction.

In past years efforts have concentrated on the development of arrays of Silicon Drift Detectors for X-ray spectroscopy. This is in stark contrast to the little effort that has been devoted to the improvement of germanium detectors, in particular for synchrotron applications. Germanium detectors have better energy resolution and are more efficient in detecting high energy photons than silicon detectors. In this context, the detector consortium of the European project LEAPS-INNOV has set an ambitious R&D program devoted to the development of a new generation of multi-element monolithic germanium detectors for X-ray detection. In order to improve the performance of the detector under development, simulations of the different detector design options have been performed. In this contribution, the efforts in terms of R&D are outlined with a focus on the modelization of the detector geometry and first performance results. These performance results show that a signal-to-background ratio larger than 1000 can be achieved in the energy range of interest from 5 keV to 100 keV.

The high brilliance and coherent beams resulting from recent upgraded synchrotron radiation facilities open the way for a large range of experiments, where detectors play a key role in the techniques and methods developed to fully exploit the upgraded synchrotron. For instance, one of the major limitations of XAFS experiment is the performance of the detectors. In order to be able to measure more challenging samples and to cope with the very high photon flux of the current and future (diffraction limited) sources, technological developments of detectors are necessary. In this framework, the germanium detector developed in the European project LEAPS-INNOV aims at improving several technological aspects. This type of detector represents a very important class of instruments for X-ray spectroscopy due to the fact that they enable to detect efficiently photons of considerable higher energy with respect to silicon detectors. The objective of this project consists in pushing the detector performance beyond the state-of-the-art. Preliminary layout and main choices for the design studies of this new detector are presented in this paper.

We report on the use of multilayer Laue lenses to focus the intense X-ray Free Electron Laser (XFEL) beam at the European XFEL to a spot size of a few tens of nanometers. We present the procedure to align and characterize these lenses and discuss challenges working with the pulse trains from this unique x-ray source.

In this paper the back-side-illuminated Percival 2-Megapixel (P2M) detector is presented, along with its characterization by means of optical and X-ray photons. For the first time, the response of the system to soft X-rays (250 eV to 1 keV) is presented. The main performance parameters of the first detector are measured, assessing the capabilities in terms of noise, dynamic range and single-photon discrimination capability. Present limitations and coming improvements are discussed.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The ever-increasing brightness of synchrotron radiation sources demands improved x-ray optics to utilise their capability for imaging and probing biological cells, nano-devices, and functional matter on the nanometre scale with chemical sensitivity. Hard x-rays are ideal for high-resolution imaging and spectroscopic applications due to their short wavelength, high penetrating power, and chemical sensitivity. The penetrating power that makes x-rays useful for imaging also makes focusing them technologically challenging. Recent developments in layer deposition techniques that have enabled the fabrication of a series of highly focusing x-ray lenses, known as wedged multi layer Laue lenses. Improvements to the lens design and fabrication technique demands an accurate, robust, in-situ and at-wavelength characterisation method. To this end, we have developed a modified form of the speckle-tracking wavefront metrology method, the ptychographic x-ray speckle tracking method, which is capable of operating with highly divergent wavefields. A useful by-product of this method, is that it also provides high-resolution and aberration-free projection images of extended specimens. We report on three separate experiments using this method, where we have resolved ray path angles to within 4 nano-radians with an imaging resolution of 45nm (full-period). This method does not require a high degree of coherence, making it suitable for lab based x-ray sources. Likewise it is robust to errors in the registered sample positions making it suitable for x-ray free-electron laser facilities, where beam pointing fluctuations can be problematic for wavefront metrology.

Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) allows structure determination of membrane proteins and time-resolved crystallography. Common liquid sample delivery continuously jets the protein crystal suspension into the path of the XFEL, wasting a vast amount of sample due to the pulsed nature of all current XFEL sources. The European XFEL (EuXFEL) delivers femtosecond (fs) X-ray pulses in trains spaced 100 ms apart whereas pulses within trains are currently separated by 889 ns. Therefore, continuous sample delivery via fast jets wastes >99% of sample. Here, we introduce a microfluidic device delivering crystal laden droplets segmented with an immiscible oil reducing sample waste and demonstrate droplet injection at the EuXFEL compatible with high pressure liquid delivery of an SFX experiment. While achieving ~60% reduction in sample waste, we determine the structure of the enzyme 3-deoxy-D-manno-octulosonate-8-phosphate synthase from microcrystals delivered in droplets revealing distinct structural features not previously reported.

X-ray computed micro-tomography (mu CT) is one of the most advanced and common non-destructive techniques in the field of medical imaging and material science. It allows recreating virtual models (3D models), without destroying the original objects, by measuring three-dimensional X-ray attenuation coefficient maps of samples on the (sub) micrometer scale. The quality of the images obtained using mu CT is strongly dependent on the performance of the associated X-ray detector i.e. to the acquisition of information of the X-ray beam traversing the patient/sample being precise and accurate. Detectors for mu CT have to meet the requirements of the specific tomography procedure in which they are going to be used. In general, the key parameters are high spatial resolution, high dynamic range, uniformity of response, high contrast sensitivity, fast acquisition readout and support of high frame rates. At present the detection devices in commercial mu CT scanners are dominated by charge-coupled devices (CCD), photodiode arrays, CMOS acquisition circuits and more recently by hybrid pixel detectors. Monolithic CMOS imaging sensors, which offer reduced pixel sizes and lowelectronic noise, are certainly excellent candidates for mu CT and may be used for the development of novel high-resolution imaging applications. The uses of monolithic CMOS based detectors such as the PERCIVAL detector are being recently explored for synchrotron and FEL applications. PERCIVAL was developed to operate in synchrotron and FEL facilities in the soft X-ray regime from 250 eV to 1 keV and it could offer all the aforementioned technical requirements needed in mu CT experiments. In order to adapt the system for a typical tomography application, a scintillator is required, to convert incoming X-ray radiation (similar to tens of KeV) into visible light which may be detected with high efficiency. Such a taper-based scintillator was developed and mounted in front of the sensitive area of the PERCIVAL imager. In this presentation we will report the setup of the detector system and preliminary results of first mu CTs of reference objects, which were performed in the TomoLab at ELETTRA.

The new European X-ray Free-Electron Laser (European XFEL) is the first X-ray free-electron laser capable of delivering intense X-ray pulses with a megahertz interpulse spacing in a wavelength range suitable for atomic resolution structure determination. An outstanding but crucial question is whether the use of a pulse repetition rate nearly four orders of magnitude higher than previously possible results in unwanted structural changes due to either radiation damage or systematic effects on data quality. Here, separate structures from the first and subsequent pulses in the European XFEL pulse train were determined, showing that there is essentially no difference between structures determined from different pulses under currently available operating conditions at the European XFEL.

The world’s first superconducting megahertz repetition rate hard X-ray free-electron laser (XFEL), the European XFEL, began operation in 2017, featuring a unique pulse train structure with 886 ns between pulses. With its rapid pulse rate, the European XFEL may alleviate some of the increasing demand for XFEL beamtime, particularly for membrane protein serial femtosecond crystallography (SFX), leveraging orders-of-magnitude faster data collection. Here, we report the first membrane protein megahertz SFX experiment, where we determined a 2.9 Å-resolution SFX structure of the large membrane protein complex, Photosystem I, a > 1 MDa complex containing 36 protein subunits and 381 cofactors. We address challenges to megahertz SFX for membrane protein complexes, including growth of large quantities of crystals and the large molecular and unit cell size that influence data collection and analysis. The results imply that megahertz crystallography could have an important impact on structure determination of large protein complexes with XFELs.

The Karabo distributed control system has been developed to address the challenging requirements of the European X-ray Free Electron Laser facility, including complex and custom-made hardware, high data rates and volumes, and close integration of data analysis for distributed processing and rapid feedback. Karabo is a pluggable, distributed application management system forming a supervisory control and data acquisition environment as part of a distributed control system. Karabo provides integrated control of hardware, monitoring, data acquisition and data analysis on distributed hardware, allowing rapid control feedback based on complex algorithms. Services exist for access control, data logging, configuration management and situational awareness through alarm indicators. The flexible framework enables quick response to the changing requirements in control and analysis, and provides an efficient environment for development, and a single interface to make all changes immediately available to operators and experimentalists.

The peak brilliance reached by today's Free-Electron Laser and Synchrotron light sources requires photon detectors matching their output intensity and other characteristics in order to fully realize the sources' potential. The Pixellated Energy Resolving CMOS Imager, Versatile And Large (Percival) is a dedicated soft X-ray imager (0.25–1 keV) developed for this purpose by a collaboration of DESY, Rutherford Appleton Laboratory/STFC, Elettra Sincrotrone Trieste, Diamond Light Source, and Pohang Accelerator Laboratory. Following several generations of prototypes, the Percival “P2M” 2-Megapixel imager—a 4.5×5 cm monolithic, stitched sensor with an uninterrupted imaging area of 4×4 cm2 (1408×1484 pixels of 27×27 μm—was produced and has demonstrated basic functionality with a first-light image using visible light. It is currently being brought to full operation in a front-illuminated configuration. The readout system being commissioned in parallel has been developed specifically for this imager which will produce—at full 300 Hz frame rate—data at 20 Gbit/s. A first wafer with eight Percival P2M chips has undergone backthinning to enable soft X-ray detection. It has been diced and chips are currently being wirebonded. We summarize here the P2M system, the project status, and show the P2M sensor's first response to visible light.

We describe the data analysis structure that is integrated into the Karabo framework to support scientific experiments and data analysis at European XFEL. The photon science experiments have a range of data analysis requirements, including online (i.e. near real-time during the actual measurement) and offline data analysis. The Karabo data analysis framework supports execution of automatic data analysis for routine tasks, supports complex experiment protocols including data analysis feedback integration to instrument control, and supports integration of external applications. The online data analysis is carried out using distributed and accelerator hardware (such as GPUs) where required to balance load and achieve near real-time data analysis throughput. Analysis routines provided by Karabo are implemented in C++ and Python, and make use of established scientific libraries. The XFEL control and analysis software team collaborates with users to integrate experiment specific analysis codes, protocols and requirements into this framework, and to make it available for the experiments and subsequent offline data analysis.

Over the last decade X-ray free-electron laser (XFEL) sources have been made available to the scientific community. One of the most successful uses of these new machines has been protein crystallography. When samples are exposed to the intense short X-ray pulses provided by the XFELs, the sample quickly becomes highly ionized and the atomic structure is affected. Here we present a webtool dubbed FreeDam based on non-thermal plasma simulations, for estimation of radiation damage in free-electron laser experiments in terms of ionization, temperatures and atomic displacements. The aim is to make this tool easily accessible to scientists who are planning and performing experiments at XFELs.

The new European X-ray Free-Electron Laser is the first X-ray free-electron laser capable of delivering X-ray pulses with a megahertz inter-pulse spacing, more than four orders of magnitude higher than previously possible. However, to date, it has been unclear whether it would indeed be possible to measure high-quality diffraction data at megahertz pulse repetition rates. Here, we show that high-quality structures can indeed be obtained using currently available operating conditions at the European XFEL. We present two complete data sets, one from the well-known model system lysozyme and the other from a so far unknown complex of a β-lactamase from K. pneumoniae involved in antibiotic resistance. This result opens up megahertz serial femtosecond crystallography (SFX) as a tool for reliable structure determination, substrate screening and the efficient measurement of the evolution and dynamics of molecular structures using megahertz repetition rate pulses available at this new class of X-ray laser source.

Unravelling the interaction of biological macromolecules with ligands and substrates at high spatial and temporal resolution remains a major challenge in structural biology. The development of serial crystallography methods at X-ray free-electron lasers and subsequently at synchrotron light sources allows new approaches to tackle this challenge. Here, a new polyimide tape drive designed for mix-and-diffuse serial crystallography experiments is reported. The structure of lysozyme bound by the competitive inhibitor chitotriose was determined using this device in combination with microfluidic mixers. The electron densities obtained from mixing times of 2 and 50 s show clear binding of chitotriose to the enzyme at a high level of detail. The success of this approach shows the potential for high-throughput drug screening and even structural enzymology on short timescales at bright synchrotron light sources.