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

描述(申请人提供)：我们建议开发具有卓越光学性能的X射线Wolter毛细反射镜，这将对许多与生物医学研究相关的现有X射线表征和分析工具产生影响。与最近可用的高亮度微焦X射线源相结合，它可以将许多X射线技术的吞吐量提高到原来的10倍，并降低初始工具采购成本和后续维护成本。对于提议的公司，我们计划将其用于我们的低于30 nm分辨率的X射线3D成像系统，包括由NIH第二阶段资金开发的原型3D成像系统，该系统针对以30 nm分辨率成像生物样本进行了优化。这种性能的提高和更低的成本相结合，将有助于使该工具在生物实验室中得到广泛应用。以30纳米分辨率对细胞、细胞团和组织进行三维X射线成像，有可能为生物系统的组织、进化和连通性打开新的洞察力，并自然地补充了生物研究人员现有的工具包。沃尔特毛细管镜还将极大地改进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的晶体结构的蛋白质结晶学，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，这些都是药物开发和了解疾病的重要工具。与X射线显微镜类似，在这些其他X射线技术中的一些特定应用中，吞吐量增益可能预期为10倍。在第二阶段项目中，我们计划改进我们的制造工艺，提高我们的计量能力，以制造点扩散功能优于1&lt；m的Wolter毛细透镜。项目叙述拟议的Wolter镜面光学系统的成功开发将使生物应用的3D X射线显微镜变得更强大、更实惠和更实用，因为它将图像采集时间从几个小时减少到几十分钟(大约10倍的吞吐量增加)。令人兴奋的能力包括对分辨率为30 nm的细胞和组织样本进行原位3D成像，这些样本在形态和功能上与自然生存状态相比几乎没有变化。除了三维X射线成像外，对于药物发现和疾病理解至关重要的其他X射线技术，如X射线衍射和小角散射，也有望从这一发展中获得类似的吞吐量增长。

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.