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

X射线结晶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，包括呼吸作用、光合作用、细胞信号、受体的激活和酶机制。由于我们有能力确定即使是最复杂的系统的高分辨率结构，我们对生物学和生物过程的看法也发生了变化。它还给现代药物发现带来了革命性的变化，基于结构的药物/先导化合物已经变得司空见惯。X射线结晶学在过去30年中取得的巨大成功在很大程度上要归功于高强度同步辐射(SR)设备的出现。在过去的几十年里，SR光源在亮度方面取得了巨大的进步，亮度增益的速度是半导体改善速度的两倍(摩尔定律)，越来越亮的光源提供的X射线光子密度越来越高，这要求光束线、光学元件和探测器得到快速发展。探测器的重大改进出现在上个世纪末，从照相板到成像板再到电荷耦合探测器(CCDs)。钻石同步加速器开始使用大型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)取代-事实上，钻石利用起源于瑞士光源的HPC探测器的开发，引领了变革的步伐。实验室来源继续发挥三个重要作用，即：(1)晶体的预筛选、它们的初始特征和确定配体/化合物/缓蚀剂的浸泡条件；(2)确定完好的衍射系统的结构(事实上，目前每年使用实验室来源确定的结构数目与1980/90年代相同)；(3)培训和装备博士生和PDRA，使他们不仅具备使用(作为用户)的深入技能，而且对仪器和数据收集的细微之处有深入的了解。实验室的光源(和相关的光学设备)也得到了改进，探测器技术也在进步，但比同步加速器落后了大约十年。直到最近，光子计数混合像素阵列硅探测器的技术才能用于实验室来源，与为同步加速器购买的探测器相比，价格只有一小部分。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来源相匹配来实现的。X射线探测器必须收集、量化和数字化输入的X射线，同时保存高精度的位置信息。最先进的新一代HPC X射线探测器可以收集具有非凡(&gt；99%)量子效率的X射线。近年来，像素尺寸的减小提高了收集数据的质量；这与提高高清晰度电视的屏幕分辨率类似。Dectris在混合像素阵列探测器方面处于领先地位，其新的Eiger范围将较小的像素尺寸与高量子效率和信噪比结合在一起。Eiger R系列是为更强的实验室信号源量身定做的，能够连续读出高计数速率，像素很小(75微米)，类似于我们目前的MAR225CCD，现在已经有12年的历史了。提供这一最新一代探测器不仅将确保Barkla实验室继续成功运行，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体。

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.