A high throughput, high resolution, and high sensitivity scanning X-ray fluoresce

描述（由申请人提供）：众所周知，微量元素在多种疾病中具有关键作用，包括癌症和神经退行性疾病，如阿尔茨海默病和威尔逊病。由于其生物学重要性，已经有许多研究使用光谱技术，如激光消融电感耦合质谱法（LA-ICP-MS）来了解组织中的绝对浓度值。同步加速器X射线荧光（XRF）的最新发展使绝对浓度值的快速高分辨率映射成为可能，并且重要的是，同时进行多种痕量元素的定量分布分析。这样的系统提供高达十亿分之几的灵敏度，以微米级分辨率映射患病组织中的微量元素。我们建议开发一种实验室扫描X射线荧光微探针的生物医学界，这将使人们有可能第一次把微量元素映射在细胞水平上目前只能在同步加速器设施。这将通过在光源、光学和探测器上的关键创新，对标准实验室XRF进行巨大改进来实现。与现有的商用微型XRF系统相比，将实现高达7200倍的荧光信号增益，从而实现实验室内生物医学应用X射线荧光映射的关键功能。拟议的第一阶段项目是一个原理验证演示，证明可以制造所需的新型XRF光源，并完成光学系统的设计。该项目的主要成果是源热性能的有限元分析，新型源阳极的五个原型，以及Wolter光学器件的设计规范。

DESCRIPTION (provided by applicant): Trace elements are well known to have critical roles in a wide variety of diseases, including cancer and neurodegenerative diseases such as Alzheimer's and Wilson's diseases. Due to their biological importance, there have been numerous studies performed with spectroscopy techniques such as laser ablation inductively coupled mass spectrometry (LA-ICP-MS) to understand absolute concentration values in tissue. More recent developments in synchrotron X-ray Fluorescence (XRF) have enabled rapid high resolution mapping of absolute concentration values, and, significantly, the quantitative distribution analysis of multiple trace elements at once. Such systems provide up to parts-per-billion sensitivity to map trace elements at micron- scale resolution in diseased tissue. We propose to develop a laboratory scanning X-ray fluorescence microprobe for the biomedical community that will make it possible for the first time to bring trace elemental mapping at the cellular level currently only achievable at synchrotron facilities. This will be achieved by bringig vast improvements to standard laboratory XRF by key innovations on the source, optics, and detector. Up to 7200X fluorescence signal gain over existing commercial micro-XRF systems will be achieved, enabling key capabilities for biomedical application x-ray fluorescence mapping within the laboratory. The proposed Phase I project is a proof-of-principle demonstration that the novel XRF source required can be manufactured and to complete design of the optics. Key deliverables of this project are finite element analysis of the source thermal performance, five prototypes of the novel source anode, and a design specification for the Wolter optics.