Development of CMOS Based Large Format X-ray Detector for Protein Crystallography

描述（由申请人提供）：我们建议开发一种廉价，但非常高质量的蛋白质晶体学探测器系统，使用有源像素矩阵CMOS（互补金属氧化物半导体）技术。我们的工作是基于现有的X射线CMOS成像系统，由Rad-icon成像公司制造。在这个项目的第一期，我们将现有探测器模块的有效面积增加了4倍，像素大小从485米增加到965米。全尺寸（50mm x 100mm）原型被制造和测试。我们将其总噪声降低了一半，并将其读出精度从12位（4,096中的1部分）提高到14位（16,384中的1部分）。最后，我们制作了小型（16像素x16像素）的原型器件，其读出被重新设计为16位相关双采样（CDS）。我们对这些设备进行了测试，并验证了CDS将读出噪声降低了6倍。在第二阶段，我们将制造具有相关双采样的全尺寸传感器。我们还将纳入额外的噪声抑制技术，特别是多个非破坏性读出。通过制造具有多个读出端口的新传感器，我们实现了并行读出，因此我们可以在不到一秒的时间内读取每个像素多次（16）次，从而提高了每次测量的可靠性。这些技术改进将充分降低噪声，我们可以实现16位精度读出，使噪声小于检测器总范围的65,536的一部分。然后，我们将开发一个完整的探测器系统，将这些模块中的12个集成在2x6阵列中，覆盖20cm x 30cm的区域。该系统将被冷却到-600摄氏度，以进一步降低噪音。我们计划推向市场的x射线探测系统，相对于现有的商用设备，在技术上将非常先进，但成本仅为其一半左右。我们的系统将大大提高结构分子生物学的科学有效性，以及他们的劳动成本效益。

DESCRIPTION (provided by applicant): We propose to develop an inexpensive, yet very high quality detector system for protein crystallography, using Active Pixel Matrix CMOS (complementary metal-oxide-semiconductor) technology. We have based this effort on an existing CMOS imaging system for X rays, manufactured by Rad-icon Imaging Corporation. During Phase I of this proposed project, we increased the active area of the existing detector module 4-fold, by doubling its pixel size from 485m to 965m. Full-scale (50mm x 100mm) prototypes were fabricated and tested. We decreased its total noise by half, and we increased its readout precision from 12-bit (1 part in 4,096) to 14- bit (1 part in 16,384). Finally, we fabricated small (16pixel x16pixel) prototype devices whose readout was redesigned with 16-bit, correlated double sampling (CDS). We test these devices and verified that CDS reduces the readout noise by up to a factor of 6. In Phase II, we will fabricate full-sized sensors with correlated double sampling. We will also incorporate additional noise suppression technology, particularly multiple non-destructive readout. By fabricating the new sensors with multiple readout ports, we enable parallel readout, so we can read each pixel many (16) times in less than one second, thus improving the reliability of each measurement. These technical improvements will reduce noise sufficiently that we can implement 16-bit precision readout such that the noise is less than one part in 65,536 of the total range of the detector. We will then develop a complete detector system, incorporating 12 of these modules in a 2x6 array, covering an area of 20cm x 30cm. This system will be cooled to -600C, to reduce the noise even more. The X-ray detection systems we plan to bring to market will be technically very advanced relative to existing commercial units, yet they will cost about half as much. Our system will greatly improve the scientific effectiveness of structural molecular biology, and the cost effectiveness of their labor. PUBLIC HEALTH RELEVANCE: 1). 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 would enhance the efficacy of protein crystallography, by improving the X-ray detector these scientists use in their home laboratory, to record the diffraction data from protein crystals they have grown. 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.