Davide Mezza

Electrons have emerged as an important complement to X-rays in crystallography, particularly for compounds that present challenges in growing crystals sufficiently large for synchrotron radiation (5–10 µm) or laboratory diffractometers (∼50 µm). Given the nature of electron-matter interactions, electron diffraction (ED) provides a way to experimentally determine the electrostatic potential of compounds. To fully harness the power of ED, we have integrated a fast, low-noise and radiation-hard 1 Megapixel JUNGFRAU detector with a modern JEOL transmission electron microscope (TEM). JUNGFRAU is a charge-integrating hybrid pixel detector, with a dynamic range of 120 MeV/pixel/frame and a maximum frame rate of 2.2 kHz in continuous mode. It can detect up to 1.3 million 200 keV electrons per pixel per second before saturation. To handle the resulting 5 GB/s raw data stream (fiberoptic; 4×10 Gbps), our system features an FPGA-based backend, Jungfraujoch , which converts raw ADC values into deposited energy and enables on-the-fly frame summation. Additionally, we developed a software package with an intuitive graphical user interface that integrates detector and microscope control. This solution provides partly automated data acquisition and post-processing, with data stored in compressed HDF5 files with comprehensive metadata. This work assesses the performance of JUNGFRAU across multiple electron energies by analyzing energy deposition and pixel spread. The complete data pipeline — from detector to user interface — is validated through an ED experiment yielding structural insights.

With the evolution of synchrotron light sources to fourth generation (diffraction-limited storage rings), the brilliance is increased by several orders of magnitude compared to third generation facilities. For example, the Swiss Light Source (SLS) has been upgraded to SLS 2.0, promising a horizontal emittance reduced by a factor of 40, and a brilliance up to two orders of magnitude (three at higher energies). A key challenge arising from the increased flux is the heightened accumulated dose in silicon sensors, which leads to a significant increase in radiation damage. This translates into an increase of both noise and dark current, as well as a reduction in the dynamic range for long exposure times, thus affecting the performance of the detector, in particular, for charge-integrating detectors. We have designed sensors with a 4 × 4 mm² pixel array featuring 16 design variations of 25 µm pitch pixels with different implant and metal sizes and tested them bump-bonded to MÖNCH 0.3, a charge integrating hybrid pixel detector readout ASIC. Following a first assessment of the functionality and performance of the different pixel designs, the assembly has been irradiated with X-rays. The variation in the tested parameters was characterized at different accumulated doses up to 100 kGy at the sensor entrance window side. The annealing dynamics at room temperature have also been measured. The results show that the default pixel design is currently not optimal and can benefit from layout changes (reduction in the inter-pixel gap area with full metal coverage of the implant). Further studies on the metal coverage over large implants could be conducted. The layout changes are, however, not sufficient for future full-sized sensors, requiring improved radiation hardness and long-term stability, and additional strategies such as focusing on detector cooling and changes in sensor technologies would be required.

To enhance the spatial resolution of the MÖNCH 25 µm pitch hybrid pixel detector, deep learning models have been trained using both simulation and measurement data. Challenges arise when comparing simulation-based deep learning models to measurement-based models for electrons, as the spatial resolution achieved through simulations is notably inferior to that from measurements. Discrepancies are also observed when directly comparing X-ray simulations with measurements, particularly in the spectral output of single pixels. These observations collectively suggest that current simulations require optimization. To address this, the dynamics of charge carriers within the silicon sensor have been studied using Monte Carlo simulations, aiming to refine the charge transport modeling. The simulation encompasses the initial generation of the charge cloud, charge cloud drift, charge diffusion and repulsion, and electronic noise. The simulation results were validated with measurements from the MÖNCH detector for X-rays, and the agreement between measurements and simulations was significantly improved by accounting for the charge repulsion.

Speed, dynamic range, and radiation hardness make hybrid pixel detectors suitable image detectors for diffraction experiments. At synchrotrons and X-ray free electron lasers they are ubiquitous. However, for electron microscopy their spatial resolution is limited by multiple scattering in the sensor layer. In this paper we examine the use of two high Z sensor materials: CdTe and GaAs, as a way to mitigate this problem. The sensors were bonded to a JUNGFRAU readout chip which is a charge integrating hybrid pixel detector developed for use at X-ray free electron lasers. Using in-pixel gain switching, it can detect single particles down to 2 keV while maintaining a dynamic range of 120 MeV/pixel/frame. The characteristics of JUNGFRAU, besides being a capable detector, make it a good tool for sensor characterization since we can measure dark current and energy deposition per pixel. The high Z material shows better spatial resolution than silicon at 200 and 300 keV, however, their practical use with integrating detectors is still limited by material defects.

Chromium compensated GaAs or GaAs:Cr sensors provided by the Tomsk State University (Russia) were characterized using the low noise, charge integrating readout chip JUNGFRAU with a pixel pitch of 75 × 75 µm² regarding its application as an X-ray detector at synchrotrons sources or FELs. Sensor properties such as dark current, resistivity, noise performance, spectral resolution capability and charge transport properties were measured and compared with results from a previous batch of GaAs:Cr sensors which were produced from wafers obtained from a different supplier. The properties of the sample from the later batch of sensors from 2017 show a resistivity of 1.69 × 10⁹ Ω/cm, which is 47% higher compared to the previous batch from 2016. Moreover, its noise performance is 14% lower with a value of (101.65 ± 0.04) e⁻ ENC and the resolution of a monochromatic 60 keV photo peak is significantly improved by 38% to a FWHM of 4.3%. Likely, this is due to improvements in charge collection, lower noise, and more homogeneous effective pixel size. In a previous work, a hole lifetime of 1.4 ns for GaAs:Cr sensors was determined for the sensors of the 2016 sensor batch, explaining the so-called “crater effect” which describes the occurrence of negative signals in the pixels around a pixel with a photon hit due to the missing hole contribution to the overall signal causing an incomplete signal induction. In this publication, the “crater effect” is further elaborated by measuring GaAs:Cr sensors using the sensors from 2017. The hole lifetime of these sensors was 2.5 ns. A focused photon beam was used to illuminate well defined positions along the pixels in order to corroborate the findings from the previous work and to further characterize the consequences of the “crater effect” on the detector operation.

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.