Water-Window Soft X-Ray Microscope for Small Laboratories

适用于小型实验室的水窗软 X 射线显微镜

• 批准号: 7803787
• 负责人: Stephen Horne
• 金额: $ 39.9万
• 依托单位: ENERGETIQ TECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-15 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7803787
• 关键词: 3-Dimensional; Address; Adoption; Area; Biological; Budgets; Cell physiology; Cells; Cellular Structures; Collection; Coupled; Data; Development; Dimensions; Disadvantaged; Disease; Electron Microscopy; Goals; Image; Imaging Techniques; Investigation; Laboratories; Lead; Left; Light; Lighting; Low Dose Radiation; Manufacturer Name; Marketing; Measures; Mechanics; Microscope; Microscopy; Optics; Output; Performance; Phase; Plasma; Preparation; Reporting; Research; Research Personnel; Resolution; Rest; Roentgen Rays; Sampling; Schedule; Shapes; Small Business Innovation Research Grant; Source; Specimen; Subcellular structure; Synchrotrons; System; Techniques; Technology; Testing; Thick; Time; United States National Institutes of Health; Vacuum; Water; Work; Writing; base; beamline; cost; design; disease diagnosis; drug discovery; improved; innovation; instrument; meetings; programs; public health relevance; tool

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.

描述（由申请人提供）：软X射线显微镜显示出巨大的前景，作为一种技术，用于成像细胞结构的分辨率远远超过可以在光学显微镜中实现的，并且具有比电子显微镜所需的简单得多的样品制备。此外，所需的较低辐射剂量（与电子显微镜相比）允许三维亚细胞结构的断层扫描研究。现有的基于同步加速器的显微镜已经显示出软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国家实验室中被绑定到大规模光源。一个合适的明亮，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（2 R44 RR 022488 -02）中，Energetiq展示了一种独特的紧凑型光源，可生成成像所需的X射线波长和强度。在随后的II期NIH SBIR计划（5 R44 RR 022488 -03）中，Energetiq构建了一个“主要证据”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，我们正在按计划和预算完成其余的计划目标。在拟议的第二阶段更新计划中，Energetiq将专注于通过增加光源亮度来显著缩短曝光时间，并将与现有制造商（Xradia，Inc.）Energetiq公司将Energetiq光源与其显微镜集成，从而加快了商用仪器的上市速度。最终目标将是为研究人员提供一种新的商业工具，用于研究亚细胞结构。 公共卫生相关性：生物学家需要以高分辨率和水合状态对整个生物细胞进行成像。目前可用的商业集成显微镜满足这些要求之一，但不能同时满足这两个要求。所谓的“水窗”中的软X射线显微镜允许完全水合细胞样品的分辨率达到20 nm，并且可以产生2-D和3-D断层图像。在水合细胞中解析亚细胞结构的能力，以及在几分钟而不是几天内创建这些图像的能力，可能会导致药物发现，疾病诊断，疾病治疗和理解基本细胞过程的更快进步。该计划将使研究人员能够广泛采用这项技术。