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

基于 CMOS 的蛋白质晶体学大幅面 X 射线探测器的开发

• 批准号: 7907127
• 负责人: EDWIN M WESTBROOK
• 金额: $ 121.6万
• 依托单位: RESEARCH DETECTORS, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7907127
• 关键词: Anodes; Area; Biological; Biological Sciences; Bite; Charge; Chemistry; Computer Architectures; Contracts; Crystallography; Data; Detection; Development; Devices; Dimensions; Dose; Effectiveness; Engineering; Equipment; Exhibits; Goals; Home environment; Image; Institution; Laboratories; Marketing; Measurement; Mechanics; Methods; Molecular Biology; Noise; Nucleic Acids; Output; Penetration; Performance; Pharmacologic Substance; Phase; Photons; Physical Chemistry; Play; Price; Process; Proteins; R43 grant; Radiation; Reading; Relative (related person); Resolution; Roentgen Rays; Role; Sampling; Scientist; Semiconductors; Signal Transduction; Small Business Innovation Research Grant; Source; Structure; System; Technology; Testing; Time; Universities; Writing; X ray diffraction analysis; X-Ray Diffraction; analog; base; computerized data processing; cost; cost effectiveness; design; detector; digital; improved; macromolecule; medical schools; metal oxide; prototype; public health relevance; quantum; sensor; small molecule

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.

描述（由申请人提供）：我们建议使用有源像素矩阵CMOS（互补金属氧化物半导体）技术开发一种廉价但质量非常高的蛋白质晶体学检测器系统。我们已经基于现有的CMOS成像系统的X射线，由Rad-icon成像公司制造的这项工作。在该项目的第一阶段，我们将现有探测器模块的有效面积增加了4倍，将其像素大小从485米增加到965米。制造并测试了全尺寸（50 mm x 100 mm）原型。我们将其总噪声降低了一半，并将其读出精度从12位（14，096）提高到14位（1/16，384）。最后，我们制作了小型（16像素x16像素）原型器件，其读出采用16位相关双采样（CDS）重新设计。我们测试了这些器件，并验证了CDS降低了读出噪声高达6倍。在第二阶段，我们将制作全尺寸的传感器与相关的双采样。我们还将采用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，我们可以实现并行读出，因此我们可以在不到一秒的时间内多次读取每个像素（16次），从而提高每次测量的可靠性。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，使噪声小于探测器总范围的65，536分之一。然后，我们将开发一个完整的探测器系统，将其中的12个模块合并为2x 6阵列，覆盖面积为20 cm x 30 cm。该系统将被冷却到-600C，以进一步降低噪音。我们计划推向市场的X射线探测系统在技术上将比现有的商业设备先进得多，但成本只有现有的一半。我们的系统将大大提高结构分子生物学的科学效率，以及劳动的成本效益。 公共卫生相关性：1）。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。目前的提议将提高蛋白质晶体学的效率，通过改进这些科学家在他们的家庭实验室中使用的X射线探测器，记录他们生长的蛋白质晶体的衍射数据。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，而且价格只有一半。