A LARGE MOSAIC CCD CAMERA FOR CRYO EM

项目描述（由申请人提供）：本计划的目标是设计及建造一个大型CCD探测器，以提供一种改良的胶片代替生物电子显微镜的直接数字记录数据。这样的系统将立即适用于大分子的低温电子显微镜（cryo-EM）和大分子复合物、细胞器和细胞子系统的3D电子断层扫描。对于分子显微镜（使用冷冻电镜），该系统将能够常规收集多达100万张大型大分子复合物的图像，促进和加速蛋白质复合物高分辨率结构的确定，而没有培养纯化材料大晶体的困难（如蛋白质晶体学的情况）。同样的新探测器技术也将允许收集跨多个空间尺度的中等分辨率3D显微镜的宽视场图像，从而能够确定组织中细胞大功能域的超分子复合物的精确组织。

DESCRIPTION (provided by applicant): The goal of the proposed project is to design and build a large mosaic of CCD detectors to provide an improved film substitute for direct digital recording of data for biological electron rnicroscopy. Such a system will be immediately applicable and beneficial to cryo-electron microscopy (cryo-EM) of macromolecules and 3D electron tomography of macromolecular complexes, organelles, and cellular subsystems. For molecular microscopy (with cryo-EM), this system will enable the routine collection of up to l million images of large macromolecular complexes, facilitating and accelerating the determination of high-resolution structures of protein complexes, without the difficulty of growing large crystals of purified materials (as is otherwise the case with protein crystallography). The same new detector technology will also allow the collection of wide-field images for intermediate resolution 3D microscopy spanning multiple spatial scales, to enable determinations of the precise organization of supramolecular complexes throughout large functional domains of cells in tissues. Building on the recent success of lens-coupled CCD camera technology, our goal is to build a new detector containing a mosaic of 9 CCD detectors, each with its own lens that can cover an overlapping portion of a scintillator screen of 15 cm x l5 cm. This mosaic detector will have a functional resolution of 5600 x 5600 pixels. We will initially design and test a single "module" of this detector with one back-side illuminated 2K x 2K pixel (13.5 gm) CCD sensor and one prototype lens. This will be followed by the design and development of a 2 x 2 mosaic of detectors and lenses. This moderately complex mosaic camera will allow us to work out all design and development issues before making the 9 CCD mosaic in the 3rd year. A significant effort during all 3 years will be to map out all detector distortions and to develop software to seamlessly stitch together detector subimages.