A Completely new Camera for Cryo EM

描述（由申请人提供）：该项目的总体目标是设计和建立一个基于直接检测主动像素检测器（APD）的最先进的摄像系统，为生物电子显微镜的直接数字记录数据提供一个大大改进的胶片替代品。该系统可立即应用于大分子的低温电子显微镜（cryo-EM）研究。新的APD将具有非常均匀的表面和格式，在10mu/mx10mu/m间距下为2000 × 2000像素。作为直接入射电子探测器，该装置不需要限制分辨率的磷光闪烁屏。每个入射电子的信噪比将比基于CCD的相机高得多（10/01 Vs 1.1），空间分辨率也更好（10微米，全宽在1/2最大值，50微米在1/100 Vs 30和200微米），该APD的读出速度也比CCD快得多（1/10秒Vs 1秒）。有了这个探测器，研究人员将能够快速收集数十万张图像的数据，大大提高所研究大分子的3D结构的分辨率。虽然微电子的设计和测试可能是昂贵的，但新的传感器使用标准的CMOS工艺，可以相当便宜地复制。事实上，在这个项目结束时，我们可以有足够的芯片来设置更多的探测器。APD的每个像素将有一个二极管，该二极管将收集入射电子在其通过敏感p外延层时沉积的电荷。它将在暴露期间收集到的卡片进行整合。在从结束时，传感器阵列的内容被读出，数字化和存储。所有的集成和读出电子器件都在0.25 μ m /m CMOS芯片表面不到1 μ m /m的范围内实现，并且对入射电子是透明的，由于敏感的p外延层位于读出电路下方并且是连续的，因此是100%透明的。我们打算分阶段进行这项研究。在第一年，我们希望通过制作和测试许多小型阵列（256x256像素）来探索不同的设计。在第二年，我们将选择最佳设计制作和休息中等尺寸的芯片（526x526像素）。在第三年，我们将制造和测试大尺寸芯片（2Kx2K像素）并设置检测器。

DESCRIPTION (provided by applicant): The overall goal of this project is to design and build a state-of-the-art camera system, based on Direct Detection Active Pixel Detector (APD) to provide a vastly improved film substitute for direct digital recording of data for biological Electron Microscopy. Such a system will be immediately applicable and beneficial to cryo-Electron Microscopy (cryo-EM) of macromolecules. The new APD will have an extremely uniform surface and format of 2000x2000 pixels at 10mu/mx10mu/m pitch. As a direct incident electron detector, this device will not require a resolution limiting phosphorescent scintillation screen. The signal to noise ratio for each incident electron will be much higher than the one with a CCD based camera (10/01 vs. 1.1) The spatial resolution is also much better (10 micron, full width at 1/2 maximum and 50 micron at 1/100 vs. 30 and 200 micron) The readout speed of this APD is also much faster than with a CCD (1/10 sec. Vs 1 sec). With this detector, researchers will be able to quickly gather data on hundreds of thousand of images, greatly improving the resolution of 3D structure of the studied macromolecules. While the design and testing of micro-electronics can be costly, the new sensor uses a standard CMOS process and can be reproduced rather inexpensively, As the matter of fact, at the end of this project, we could have enough chips to set up many more detectors. Each pixel of the APD will have a diode that will collect the charges deposited by an incident electron in its passage through a sensitive p-epitaxial layer. It will integrate the collected chards during and exposure period. At the conclusion of the from, the contents of the sensor array are than read out, digitized and stored. All of the integration and read out electronics are implemented within less than 1mu/m of the surface of a 0.25 mu/m CMOS chip, and are transparent to the incident electrons, is 100% due to the fact that the sensitive p-epitaxial layer lies beneath the readout circuitry and is continuous. We intend a phased approach to this research. During the first year, we would like to explore different designs by making and testing many small arrays (256x256 pixels). In the 2nd year, we will select the best design to make and rest medium size chip (526x526 pixels). In the 3rd year we will make and test the large size chip (2Kx2K pixels) and set up the detector.