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

描述(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，如阿尔茨海默氏症和威尔逊氏病。由于它们在生物学上的重要性，已经有许多研究利用光谱学技术，如激光消融电感耦合质谱仪(LA-ICPMS)来了解组织中的绝对浓度。同步加速器X射线荧光(XRF)的最新发展使得能够快速、高分辨率地绘制绝对浓度值，更重要的是，能够同时对多种痕量元素进行定量分布分析。这种系统提供了高达十亿分之几的灵敏度，可以在微米级分辨率上绘制疾病组织中的微量元素图。我们建议为生物医学界开发一种实验室扫描X射线荧光微探测器，这将首次使在细胞水平上进行痕量元素图谱成为可能，目前只有在同步加速器设施中才能实现。这将通过在光源、光学和探测器上的关键创新带来对标准实验室XRF的巨大改进来实现。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射线荧光测绘的关键能力。拟议的第一阶段项目是一个原则证明，证明可以制造所需的新型XRF源并完成光学设计。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.