Phase plate holder for transmission electron microscopy

描述（由申请人提供）：我们申请的目的是开发硬件和程序，使研究人员能够在透射电子显微镜中实际利用物镜透镜后焦平面中的相位板。使用精确定位的相位板可以提高电子断层扫描的分辨率，并且在使用单粒子方法时也可以提高吞吐量。我们的具体目标是提供一种相位板系统，其将包括改进的物镜孔径保持器，该物镜孔径保持器结合有（1）压电定位系统，（2）避免污染的加热器，以及（3）用于与静电相位板一起使用的电馈通。简单地将原始物镜孔径保持器与Hummingbird相位板保持器交换将允许几乎任何低温EM配备有相位板。这种保持器的成本将大大低于任何其他技术，可以产生类似的改善冷冻水合标本的成像。通过与沃兹沃斯中心NIH生物技术资源的生物复杂性可视化资源（RVBC）密切合作，我们将开发一种新的相板保持器，演示其用途并发布结果。我们的目的是开发和商业化一个具有成本效益的系统，使这些技术成为生物研究界广泛使用。这项提案将开发工具，使生物学家能够更清楚地了解细胞的结构和功能。这些知识是医学研究和实践的无数领域的基础。

DESCRIPTION (provided by applicant): The objective of our application is to develop hardware and procedures that will allow researchers to practically utilize phase plates in the back focal plane of the objective lens in a Transmission Electron Microscope. Use of precisely positioned phase plates can increase resolution in electron tomography, and also increase throughput when using the single-particle approach. Our specific aim is to provide a phase plate system that will include a modified objective aperture holder that incorporates (1) a piezo positioning system, (2) a heater to avoid contamination, and (3) an electrical feed-through for use with electrostatic phase plates. Simply exchanging the original objective aperture holder with the Hummingbird phase plate holder will allow nearly any cryo-EM to be equipped with a phase plate. The cost of this holder will be substantially lower than any other technology that can yield a similar improvement in imaging of frozen-hydrated specimens. In close collaboration with the Resource for the Visualization of Biological Complexity (RVBC) at the Wadsworth Center's NIH Biotechnological Resource, we will develop a new phase plate holder, demonstrate its use, and publish the results. It is our intent to develop and commercialize a cost effective system that will enable these techniques to become widely available to the biology research community. This proposal will develop tools that allow biologists to get a clearer picture of the structure and function of the cell. This knowledge is fundamental to innumerable areas of medical research and practice.