Development of a CMOS-based Very Large-Format X-ray Detector for Synchrotron Beam

描述（由申请人提供）：我们建议开发一个大型的，高性能的X射线检测器系统，用于蛋白质晶体在同步加速器光束线，使用有源像素矩阵传感器CMOS（互补金属氧化物半导体）技术。这将是一个47.05cm x 44.32cm（4700 x 4428像素）的1005米像素系统。在帧读出期间，每个像素将仅在225秒内处于非活动状态;整个探测器将在0.033秒内读出。总的电子系统噪声将小于来自单个12 keV X射线光子的信号，并且也小于其16位精度读出中的单个数字间隔。它的空间分辨率、动态范围、灵敏度和探测量子效率将等于或超过目前的CCD系统。零售成本将是当今商业CCD系统的一半，并且大大低于瑞士PILLENT（www.dectris.com），我们的系统将明确与之竞争。它将被设计为在没有定时快门的情况下工作，允许样品晶体连续旋转。在今天为蛋白质晶体学设计的同步加速器X射线光束线中，占主导地位的检测器系统是CCD传感器阵列，通过锥形光纤耦合到磷光体膜（Westbrook & Necrosis，1997）。这些系统非常昂贵：一个31.5cm x 31.5cm的探测器系统目前的价格为845，000美元。虽然这些系统很好，但它们可以更好。最近，一种硅像素阵列探测器系统（SPAD）已经进入市场：PILLENT 6 M，这是日内瓦大型强子对撞机粒子加速器的ATLAS探测器系统的副产品。它的价格是同类CCD系统的两倍多，提供了比CCD更有趣的性能增强，但也存在设计问题（它来自高能物理学，而不是分子生物学！）。我们认为，在这个建议中，CMOS有源像素矩阵系统，明确设计的结构生物学的结构生物学家，提供了所有的优点，SPAD系统没有它的缺点，并在相当大的成本节约。 公共卫生相关性：蛋白质晶体学是生物科学和药物开发的成熟且重要的使能技术，用于确定大生物分子（蛋白质和核酸）的结构。目前的建议将提高蛋白质晶体学的效率，通过改进X射线探测器，记录衍射数据的蛋白质晶体在同步加速器用户设施。我们希望开发的检测器比蛋白质晶体学家现在使用的检测器更快，分辨率更高，精度更高，效率更高，而且价格将是竞争对手的一半。

DESCRIPTION (provided by applicant): We propose to develop a large, high performance X-ray detector system for protein crystallography at synchrotron beamlines, using Active Pixel Matrix Sensor CMOS (complementary metal-oxide-semiconductor) technology. It will be a 47.05cm x 44.32cm (4700 x 4428 pixel) system of 1005m pixels. Each pixel will be inactive for just 225s during frame readout; the entire detector will be read out in 0.033s. The total electronic system noise will be less than the signal from a single 12keV X-ray photon, and also less than a single digital interval in its 16-bit precision readout. Its spatial resolution, dynamic range, sensitivity, and detective quantum efficiency will equal or exceed those of current CCD systems. The retail cost will be half that of today's commercial CCD systems, and substantially less than the Swiss PILATUS (www.dectris.com), against which our system will explicitly compete. It will be designed to operate without a timing shutter, allowing the sample crystal to rotate continuously. At synchrotron X-ray beamlines designed for protein crystallography today, the dominant detector systems are arrays of CCD sensors, coupled to a phosphor film by tapered fiberoptics (Westbrook & Naday, 1997). These systems are expensive: a 31.5cm x 31.5cm detector system today costs $845,000. While these systems are good, they could be better. Recently, a silicon pixel array detector system (SPAD) has arrived on the market: the PILATUS 6M, a spin-off from the ATLAS detector system at the LHC particle accelerator in Geneva. Over twice as expensive as a comparable CCD system, it provides interesting performance augmentations over CCDs but also exhibits design problems (it derives from high-energy physics, not molecular biology!). We argue in this proposal that a CMOS active pixel matrix system, explicitly designed for structural biology by structural biologists, offers all the advantages of a SPAD system with none of its disadvantages, and at considerable cost savings. PUBLIC HEALTH RELEVANCE: Protein crystallography is a mature and important enabling technology for the biological sciences and in pharmaceutical development, for determining the structures of large biological molecules: proteins and nucleic acids. The present proposal will enhance the efficacy of protein crystallography, by improving the X-ray detectors that record the diffraction data from protein crystals at synchrotron user facilities. The detector we wish to develop is faster, higher-resolution, higher precision, and more efficient than the detectors now used by protein crystallographers, and it will be half the price of its competitors.