Water-Window Soft X-Ray Microscope for Small Laboratories

描述(申请人提供)：软X射线显微镜显示出巨大的前景，作为一种成像细胞结构的技术，其分辨率远远超过光学显微镜所能达到的水平，而且样品制备比电子显微镜所需的要简单得多。此外，所需的较低辐射剂量(与电子显微镜相比)允许对三维亚细胞结构进行断层扫描研究。现有的基于同步加速器的显微镜已经显示了软X射线显微镜作为研究工具的潜力，但它们的缺点是仅在少数几个国家实验室被捆绑在巨大的光源上。适当明亮、紧凑、低成本的光源是实现商业生物软X射线显微镜所需的使能创新。在第一阶段NIH SBIR计划(2R44RR022488-02)中，Energetiq展示了一种独特的、紧凑的光源，可以产生成像所需的X射线波长和强度。在接下来的第二阶段NIH SBIR计划(5R44RR022488-03)中，Energetiq建造了一个“原则证明”显微镜。在第二阶段计划还剩三个月的时候，几乎所有的主要计划目标都已经实现，我们正在按部就班地在预算内完成计划的其余目标。在拟议的第二阶段更新计划中，Energetiq将专注于通过提高光源亮度来显著缩短曝光时间，并将与现有制造商(XRadia，Inc.)合作。此外，我们还开发了一种新型X射线显微镜，将Energetiq源与其显微镜相结合，从而加快了商用仪器上市的速度。最终目标将是一种新的商业工具，供研究人员用于研究亚细胞结构。 与公共卫生相关：生物学家需要以高分辨率对整个生物细胞进行成像，并使其处于水合状态。目前可用的商用集成显微镜满足其中一种要求，但不能同时满足这两种要求。软X射线显微镜在所谓的“水窗口”中，使完全水合的细胞样本的分辨率达到20纳米，并可以产生2-D和3-D断层图像。能够在水合细胞中分解亚细胞结构，并在几分钟而不是几天内产生这些图像，可能会在药物发现、疾病诊断、疾病治疗和理解基本细胞过程方面取得更快的进展。拟议的计划将使研究人员能够广泛采用这项技术。

DESCRIPTION (provided by applicant): Soft x-ray microscopy shows enormous promise as a technique for imaging cellular structures at resolutions well beyond what can be achieved in optical microscopes, and with much simpler sample preparation than is required for electron microscopy. In addition, the lower radiation dose required (compared to electron microscopy) allows tomographic investigation of subcellular structures in three dimensions. Existing synchrotron based microscopes have shown the potential of the soft x-ray microscope as a research tool, but they have the disadvantage of being tied to a massive light source at only a few national laboratories. A suitably bright, compact, low cost light source is the enabling innovation needed to realize a commercial biological soft x-ray microscope. In a Phase I NIH SBIR program (2R44RR022488-02) Energetiq demonstrated a unique, compact light source that generates the required x-ray wavelength and intensity for imaging. In the following Phase II NIH SBIR program (5R44RR022488-03) Energetiq constructed a "proof-of-principal" microscope. With three months left to go in the Phase II program, nearly all major program goals have been met, and we are on track to completing the rest of the program goals on schedule and within budget. In the proposed Phase II Renewal program, Energetiq will focus on significantly shortening exposure time through increasing the source brightness and will work with an existing manufacturer (Xradia, Inc.) of x-ray microscopes to integrate the Energetiq source with their microscope, thus accelerating the point at which a commercial instrument will be available in the market. The ultimate goal will be a new commercial tool for researchers to use in studying subcellular structures. PUBLIC HEALTH RELEVANCE: Biologists have a need to image whole biological cells at high resolution and in their hydrated state. Currently available commercial, integrated microscopes satisfy one of these requirements but not both. Soft x-ray microscopy in the so-called 'water window' allows resolution to 20nm for fully hydrated cell samples, and can produce 2-D and 3-D tomographic images. The ability to resolve subcellular structures in hydrated cells, and to create those images in minutes rather than days, could lead to more rapid advances in drug discovery, disease diagnosis, disease treatment and in the understanding of fundamental cellular processes. The proposed program will enable the widespread adoption of this technique by researchers.