A new generation of Crystallographic detector for Multi-user Barkla X-ray laboratory

x射线晶体学提供了观察蛋白质和RNA/DNA分子中最高水平细节的机会。它提供了许多生物过程的无与伦比的知识，包括呼吸，光合作用，细胞信号，受体的激活和酶的机制。我们思考生物学和生物过程的方式已经发生了转变，因为我们有能力确定最复杂系统的高分辨率结构。它还彻底改变了现代药物的发现，基于结构的药物/铅化合物已经变得司空见惯。在过去的30年里，x射线晶体学取得了巨大的成功，这在很大程度上要归功于高强度同步辐射（SR）设备的可用性。在过去的几十年里，SR光源在亮度方面的性能取得了巨大的进步，其中亮度增益是半导体（摩尔定律）改进速度的两倍。越来越亮的光源所传递的x射线光子密度不断增加，这要求光束线、光学元件和探测器的快速发展。探测器从照相板到像板再到电荷耦合器件（ccd）的重大改进出现在上世纪末。DIAMOND同步加速器开始使用使用大型ccd的MX光束线，但所有这些都已被光子计数混合像素阵列硅探测器（HPC）所取代——实际上，DIAMOND利用起源于瑞士光源的HPC探测器的发展设定了变革的步伐。实验室来源继续发挥三个重要作用，即(i)晶体的预筛选，它们的初始表征和建立配体/化合物/抑制剂的浸泡条件；（ii）确定井衍射系统的结构（事实上，目前每年使用实验室光源确定的结构数量与20世纪80年代/90年代相同）和（iii）培训和装备博士生和PDRA，不仅在使用（作为用户）方面有深入的技能，而且要深入了解仪器以及数据收集的微妙之处。实验室光源（和相关的光学）也得到了改善，探测器技术也在进步，但比同步加速器落后十年左右。直到最近，光子计数混合像素阵列硅探测器的技术才被用于实验室，其价格仅为用于同步加速器的探测器的一小部分。这种价格的降低是通过将这些新一代HPC探测器的规格与实验室源相匹配来实现的。x射线探测器必须收集、量化和数字化入射的x射线，同时保持高度精确的位置信息。最先进的新一代HPC x射线探测器可以以特殊的（bbb99 %）量子效率收集x射线。近年来，像素尺寸的减小提高了所收集数据的质量；类似于提高高清电视的屏幕分辨率。Dectris在混合像素阵列探测器方面处于领先地位，他们的新EIGER系列将小像素尺寸与高量子效率和信噪比相结合。EIGER R系列是为更强烈的实验室光源量身定制的，具有连续读出的高计数率，并且具有小（75微米）像素，类似于我们目前的MAR225CCD，它已经有12年的历史了。这种最新一代探测器的提供不仅将确保Barkla实验室的持续成功运行，还将增强我们每周衍射系统的能力，包括膜蛋白晶体和多组分复合物。

X-ray crystallography offers the opportunity to observe highest level of details in protein and RNA/DNA molecules. It has delivered unrivalled knowledge of many biological processes including respiration, photosynthesis, cell signalling, receptor's activation and enzymatic mechanisms. The way we think of biology and biological processes has transformed due to our ability to determine high-resolution structures of even the most complex systems. It also has revolutionized modern drug discovery and structure-based drug/lead-compounds have become a commonplace. The tremendous success of X-ray crystallography over the last 30 years has largely been due to the availability of highly intense Synchrotron Radiation (SR) facilities. During the last couple of decades, the SR sources have seen tremendous progress in the performance in terms of brightness where the brightness gain has been twice as fast as the rate of improvement in semiconductors (Moore's law), The increasing X-ray photon density delivered by the increasingly brighter sources has required rapid development in beamlines, optical elements and detectors. A major improvement in detectors from photographic plates to image plate to Charged Coupled Detectors (CCDs) emerged at the end of last century. DIAMOND Synchrotron opened its operation with MX beamlines using large CCDs but all of these have been replaced by photon counting hybrid pixel array silicon detectors (HPC) - in fact DIAMOND set the pace of change capitalizing on the development of HPC detectors that originated at the Swiss Light Source. The laboratory sources have continued three important roles, namely (i) pre-screening of crystals, their initial characterisation and establishment of soaking conditions of ligands/compounds/inhibitors, (ii) determination of structures of well diffracting systems (in fact the number of structures determined using laboratory sources per annum currently is the same as in the 1980s/90s) and (iii) train and equip PhD students and PDRA with in-depth skills not just in the use (as a user) but acquire in-depth understanding of instrumentation as well as the subtleties of data collection. The laboratory sources (and associated optics) have also improved and detector technology is also advancing but a decade or so behind the synchrotron. Only recently the technology of photon counting hybrid pixel array silicon detectors has become available for laboratory sources at a fraction of the price compared to detectors that are being bought for synchrotrons. This reduction in price has been achieved by matching the specifications of these new generations of HPC detectors to the laboratory sources. X-ray detectors must collect, quantize and digitize incoming X-rays while preserving highly precise location information. State-of-the-art new generation HPC X-ray detectors can collect X-rays with exceptional (>99 %) quantum efficiency. In recent years reduction of pixel size has increased the quality of the data collected; similar to increasing screen resolution in high definition televisions. Dectris have led the way in hybrid pixel array detectors and their new EIGER range combine small pixel size with high quantum efficiency and signal to noise. The EIGER R range is tailored for more intense laboratory sources and is capable of high-count rates with continuous readout and have small (75 microns) pixels, similar to our current MAR225CCD, which is now 12 years old. The provision of this latest generation of detector will not only ensure continued successful operation of the Barkla laboratory but also will enhance our capabilities for weekly diffracting systems including membrane protein crystals and multi-component complexes.