Development of Wolter Capillary Condenser for High Throughput X-ray Microscopy

描述（由申请人提供）：我们建议开发具有出色光学特性的X射线Wolter毛细管镜，这将影响与生物医学研究相关的许多现有X射线表征和分析工具。与最近可用的高亮度微焦点X射线源相结合，它可以将许多X射线技术的吞吐量提高10倍，并降低初始工具购买成本和后续维护成本。对于提出申请的公司，我们计划将其用于我们的X射线3D成像系统中，分辨率为30 nm以下，包括在NIH第二阶段资助下开发的原型3D成像系统，该系统针对30 nm分辨率的生物样本进行了优化。这种性能改进和较低成本的结合将有助于使该工具在生物实验室中广泛部署。30 nm分辨率的细胞、细胞簇和组织的3D X射线成像有可能为生物系统的组织、进化和连通性提供新的见解，并自然地补充了生物研究人员现有的工具集。Wolter毛细管镜还将大大提高许多其他成熟的相关X射线技术的性能，包括用于确定蛋白质和病毒晶体结构的蛋白质晶体学，以及用于在体外和体内研究天然溶液中的生物大分子的小角散射，这是药物开发和理解疾病的重要工具。与X射线显微镜类似，对于这些其他X射线技术中的某些特定应用，可以预期10倍的吞吐量增益。在第二阶段项目期间，我们计划改进我们的制造工艺并提高我们的计量能力，以允许制造点扩散函数优于1 <m的Wolter毛细管透镜。成功开发拟议的Wolter反射镜光学器件将使生物应用的3-D X射线显微镜功能更强大，价格更实惠，并且通过将图像采集时间从几个小时减少到几十分钟（约10倍的吞吐量增益）而实用。令人兴奋的功能包括具有30 nm分辨率的细胞和组织标本的原位3D成像，这些细胞和组织标本与其自然生活状态相比几乎没有发生形态和功能变化。除了3-D X射线成像，其他X射线技术，如X射线衍射和小角度散射，对药物发现和疾病的理解至关重要，可以预期从这一发展类似的吞吐量增加。

DESCRIPTION (provided by applicant): We propose to develop the x-ray Wolter capillary mirror with outstanding optical properties that will impact many existing x-ray characterization and analysis tools relevant to biomedical research. In combination with recently available high brightness microfocus x-ray sources, it could increase the throughput of many x-ray techniques up to 10 times and reduce initial tool purchase cost and subsequent maintenance cost. For the proposing company, we plan to use it in our x-ray 3D imaging systems with sub-30 nm resolution, including a prototype 3D imaging system developed under a NIH phase II funding, which is optimized for imaging biological samples at 30nm resolution. The combination of this performance improvement and lower cost will help to make the tool widely deployed in biological laboratories. 3D x-ray imaging of cells, cell clusters and tissues at 30nm resolution has the potential to open new insights into the organization, evolution and connectivity of biological systems and naturally complements the already available toolset for biological researchers. The Wolter capillary mirror will also substantially improve the performance of many other well established, relevant x-ray techniques, including protein crystallography for determination of crystallographic structures of proteins and viruses, and small angle scattering for studying biological macromolecules in native solution both in vitro and in vivo, which are important tools for drug development and the understanding of disease. Similar to that for x-ray microscopy, a throughput gain of 10X may be expected for some specific applications in these other x-ray techniques. During the phase II project, we plan to refine our fabrication processes and improve our metrology capability to allow the fabrication of Wolter capillary lenses with a point spread function better than 1 <m. Project Narrative Successful development of the proposed Wolter mirror optic will make 3-D x-ray microscopy for biological applications more powerful, affordable, and practical by reducing image acquisition times from several hours to tens of minutes (approximately 10X throughput gain). Exciting capabilities include in-situ 3D imaging of cell and tissue specimens with 30 nm resolution that have undergone little morphological and functional change from their natural living state. In addition to 3-D x-ray imaging other x-ray techniques, such as x-ray diffraction and small angle scattering, critical to drug discovery and understanding of disease, can expect a similar throughput increase from this development.