Pixel sensitivity variation in a CdTe-Medipix2 detector using poly-energetic x-rays

We have a 1-mm-thick cadmium telluride (CdTe) sensor bump-bonded to a Medipix2 readout chip. This detector has been characterized using a poly-energetic x-ray beam. Open beam images (i.e. without an attenuating specimen between the x-ray source and the detector) have been acquired at room temperature using the MARS-CT system. Profiles of various rows and columns were analyzed for one hundred, 35-ms exposures taken with a bias voltage of -300 V (operating in electron collection mode). A region of increased sensitivity is observed around the edges of the detector. A reasonably periodic, repeatable variation in pixel sensitivity is observed. Some small regions with very low sensitivity and others with zero signals are also observed. Surrounding these regions are circular rings of pixels with higher counts. At higher flux (higher tube current in the x-ray source) there is evidence of saturation of the detector assembly. In this paper we present our understanding of the origin of these features and demonstrate the improved image quality obtained after correcting for these variations

Study of the internal quantum efficiency of FBK sensors with optimized entrance windows

Single-photon detection of X-rays in the energy range of 250 eV to 1 keV is difficult for hybrid detectors because of the low quantum efficiency and low signal-to-noise ratio. The low quantum efficiency is caused by the absorption of soft X-rays in the entrance window of the silicon sensors. The entrance window consists of an insensitive layer on the surface and a highly doped layer, which is typically from a few hundred nanometers to a couple of micrometers thick and is comparable to the absorption depth of soft X-ray photons (e.g. the attenuation length of 250 eV X-ray photons is ∼100 nm in silicon). The low signal-to-noise ratio is mainly caused by the small signal amplitude (e.g. ca. 70 electrons for 250 eV X-ray photons in silicon) with respect to the electronic noise. To improve the quantum efficiency, the entrance window must be optimized by minimizing the absorption of soft X-rays in the insensitive layer, and reducing charge recombination at the Si-SiO2 interface and in the highly doped region. Low gain avalanche diodes (LGADs) with a multiplication factor between 5 and 10 increase the signal amplitude and therefore improve the signal-to-noise ratio for soft X-rays, enabling single-photon detection down to 250 eV. Combining LGAD technology with an optimized entrance window technology can thus allow hybrid detectors to become a useful tool also for soft X-ray detection. In this work we present the optimization of the entrance window by studying the internal quantum efficiency of eight different process technology variations. The sensors are characterized using light emitting diodes with a wavelength of 405 nm. At this wavelength, the light has an absorption depth of 125 nm, equivalent to that of 276 eV X-rays. The best variation achieves an internal quantum efficiency of 0.992 for 405 nm UV light. Based on this study, further optimization of the quantum efficiency for soft X-rays detection is planned

Development of LGAD sensors with a thin entrance window for soft X-ray detection

We show the developments carried out to improve the silicon sensor technology for the detection of soft X-rays with hybrid X-ray detectors. An optimization of the entrance window technology is required to improve the quantum efficiency. The LGAD technology can be used to amplify the signal generated by the X-rays and to increase the signal-to-noise ratio, making single photon resolution in the soft X-ray energy range possible. In this paper, we report first results obtained from an LGAD sensor production with an optimized thin entrance window. Single photon detection of soft X-rays down to 452 eV has been demonstrated from measurements, with a signal-to-noise ratio better than 20

The positive impacts of Real-World Data on the challenges facing the evolution of biopharma.

Demand for healthcare services is unprecedented. Society is struggling to afford the cost. Pricing of biopharmaceutical products is under scrutiny, especially by payers and Health Technology Assessment agencies. As we discuss here, rapidly advancing technologies, such as Real-World Data (RWD), are being utilized to increase understanding of disease. RWD, when captured and analyzed, produces the Real-World Evidence (RWE) that underpins the economic case for innovative medicines. Furthermore, RWD can inform the understanding of disease, help identify new therapeutic intervention points, and improve the efficiency of research and development (R&D), especially clinical trials. Pursuing precompetitive collaborations to define shared requirements for the use of RWD would equip service-providers with the specifications needed to implement cloud-based solutions for RWD acquisition, management and analysis. Only this approach would deliver cost-effective solutions to an industry-wide problem

Resveratrol Targeting of Carcinogen-Induced Brain Endothelial Cell Inflammation Biomarkers MMP-9 and COX-2 is Sirt1-Independent

The occurrence of a functional relationship between the release of metalloproteinases (MMPs) and the expression of cyclooxygenase (COX)-2, two inducible pro-inflammatory biomarkers with important pro-angiogenic effects, has recently been inferred. While brain endothelial cells play an essential role as structural and functional components of the blood-brain barrier (BBB), increased BBB breakdown is thought to be linked to neuroinflammation. Chemopreventive mechanisms targeting both MMPs and COX-2 however remain poorly investigated. In this study, we evaluated the pharmacological targeting of Sirt1 by the diet-derived and antiinflammatory polyphenol resveratrol. Total RNA, cell lysates, and conditioned culture media from human brain microvascular endothelial cells (HBMEC) were analyzed using qRT-PCR, immunoblotting, and zymography respectively. Tissue scan microarray analysis of grade I–IV brain tumours cDNA revealed increased gene expression of Sirt-1 from grade I–III but surprisingly not in grade IV brain tumours. HBMEC were treated with a combination of resveratrol and phorbol 12-myristate 13-acetate (PMA), a carcinogen known to increase MMP-9 and COX-2 through NF-κB. We found that resveratrol efficiently reversed the PMA-induced MMP-9 secretion and COX-2 expression. Gene silencing of Sirt1, a critical modulator of angiogenesis and putative target of resveratrol, did not lead to significant reversal of MMP-9 and COX-2 inhibition. Decreased resveratrol inhibitory potential of carcinogen-induced IκB phosphorylation in siSirt1-transfected HBMEC was however observed. Our results suggest that resveratrol may prevent BBB disruption during neuroinflammation by inhibiting MMP-9 and COX-2 and act as a pharmacological NF-κB signal transduction inhibitor independent of Sirt1

Segmented flow generator for serial crystallography at the European X-ray free electron laser

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