High Speed Detector for Time-Resolved Research at BioCARS

描述（由申请人提供）：该项目申请资金用于购买最先进的大面积快速读出电荷耦合器件、X射线区域探测器和探测器支架，安装在由BioCARS/芝加哥大学在阿贡国家实验室高级光子源操作的14-ID-B插入器件光束线上。该光束线是自1992年以来由NCRR/NIH资助的基于同步加速器的结构生物学国家设施的旗舰。该设施向所有合格的科学家开放，是先进光子源最具生产力的光束线之一，这是由我们的BioCARS用户每年发表的同行评审科学论文数量（包括顶级期刊上的论文）来判断的。该设施在时间分辨单晶衍射和BSL 3级生物危害安全检测方面具有世界领先的能力。 BioCARS的研究和开发集中在时间分辨X射线晶体学的应用上。我们的用户在该领域和更传统的静态晶体学中进行合作和服务研究。我们目前使用了七年的X射线探测器具有相对较小的有效面积和相对较长的读出时间，这使得它不适合许多用户实验。第一个排除了它的使用在长晶体检测器的距离，这既增强了背景和阻碍分离的衍射斑点与晶体与大晶胞;第二个使其不适合记录连续的衍射图案在毫秒的时间范围内，因为是有利的后续较慢，往往是不可逆的反应在这个范围内。新的探测器需要设计、建造和安装全自动底座，以便相对于晶体和X射线束灵活地定位探测器。 我们的用户使用该检测器检测的晶体包括致病病毒的晶体，其中一些（例如西尼罗河病毒）是人类病原体，另一些是动物、植物或昆虫病原体。其他晶体具有更直接的生物医学意义，例如胰岛素转化酶的晶体，其中成功的结构测定可能为基于结构的药物设计开辟道路。还有一些是从阐明其分子作用机制的角度，通过时间分辨或静态晶体学进行研究的。同样，对机制的理解（特别是对短寿命中间体的结构的理解）直接支持了药物设计。

DESCRIPTION (provided by applicant): The project requests funds for purchase of a state-of-the-art, large area, fast readout, charge coupled device, X-ray area detector and detector mount, to be installed on the 14-ID-B insertion device beam line operated by BioCARS/University of Chicago at the Advanced Photon Source, Argonne National Laboratory. This beam line is the flagship of a national facility for synchrotron-based structural biology funded since 1992 by NCRR/NIH. The facility is open to all qualified scientists, and is one of the most productive beam lines at the Advanced Photon Source as judged by the number of peer- reviewed scientific papers - including those in the top journals - published annually by our BioCARS users. The facility offers world-leading capabilities in time-resolved single crystal diffraction, and in the safe examination of biohazards at the BSL3 level. BioCARS research and development has concentrated on applications in time- resolved X-ray crystallography. Our users conduct both collaborative and service research in that area and in somewhat more conventional, static crystallography. Our present seven-year-old X-ray detector has a relatively small active area and a relatively long readout time, which renders it unsuited to many user experiments. The first precludes its use at long crystal-to-detector distances, which both enhances the background and hinders the separation of diffraction spots from crystals with large unit cells; the second makes it unsuitable for recording sequential diffraction patterns in the millisecond time range, as is advantageous for following slower, often irreversible reactions in this range. The new detector requires the design, construction and installation of a fully-automated mount, to position the detector flexibly with respect to the crystal and X-ray beam. Crystals to be examined using this detector by our users include those of pathogenic viruses, some of which e.g. West Nile virus are human pathogens and others of which are animal, plant or insect pathogens. Other crystals are of more direct biomedical interest e.g. crystals of insulin converting enzymes, in which a successful structure determination may open up leads for structure-based drug design. Yet others are studied from the point of view of elucidating their molecular mechanism of action, by time-resolved or static crystallography. Again, an understanding of mechanism (and in particular, of the structures of short-lived intermediates) directly underpins drug design.