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

描述(申请人提供)：我们计划开发一个大型的，高性能的X射线同步光束线蛋白质结晶学探测器系统，使用有源像素矩阵传感器(互补金属氧化物半导体)技术。它将是一个47.05厘米x 44.32厘米(4700 x 4428像素)的1005M像素系统。在帧读出期间，每个像素将仅处于非活动状态225秒；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12keV X射线光子的信号，并且在其16位精度读出中也小于单个数字间隔。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现有的CCD系统。零售成本将是目前商用CCD系统的一半，大大低于瑞士Pilatus(www.dectris.com)，我们的系统将与之竞争。它将被设计为在没有定时快门的情况下操作，允许样品晶体连续旋转。在今天为蛋白质结晶学设计的同步加速器X射线光束线上，主要的探测器系统是通过锥形光纤耦合到荧光膜的CCD传感器阵列(Westbrook&Naday，1997)。这些系统价格不菲：如今一个31.5厘米x 31.5厘米的探测器系统售价为84.5万美元。虽然这些系统很好，但它们可能会更好。最近，一种硅像素阵列探测器系统(SPAD)上市：Pilatus 6M，它是日内瓦LHC粒子加速器ATLAS探测器系统的副产品。它的价格是可比的CCD系统的两倍多，它提供了比CCD有趣的性能增强，但也存在设计问题(它来自高能物理，而不是分子生物学！)。在这项建议中，我们认为由结构生物学家专门为结构生物学设计的CMOS有源像素矩阵系统提供了SPAD系统的所有优点而没有其缺点，并且以相当大的成本节省了成本。 与公共卫生相关：蛋白质结晶学是一项成熟而重要的技术，可用于生物科学和药物开发，用于确定生物大分子的结构：蛋白质和核酸。目前的建议将通过改进同步加速器用户设施中记录蛋白质晶体衍射数据的X射线探测器来提高蛋白质结晶学的效率。我们希望开发的探测器比蛋白质结晶学家现在使用的探测器更快、更高分辨率、更高精度、更高效，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.