A sub-cellular micro x-ray fluorescence system for elemental imaging at fast acquisition times in biological tissue

成像元素分布和浓度的能力对于各种生物医学成像越来越重要。 领域的几乎所有基本的生物学途径都需要金属结合蛋白和微量元素。 元素，以及越来越多的病理学现在与-或假设与-痕量 元素失调，包括不育和神经退行性疾病，如阿尔茨海默氏症和威尔逊氏症。 此外，包含金属药物和基于纳米颗粒的治疗的新型药物正在增加， 并且改进的此类药物的合理设计方法需要化学成像来确定 这些药物的吸收和清除机制。 目前，元素成像的实验室方法被限制在10微米左右， 允许关键的亚细胞元素的理解，可以加强突破性的见解。的 研究人员对微米级分辨率化学成像的访问仅限于在 同步加速器，这是一个主要的瓶颈。在这个小企业创新和研究补助金，我们建议， 几项重大创新，为生物医学领域开发了第一个实验室亚细胞microXRF 社区，开辟了实现实验室nanoXRF的前进道路。该系统将实现微米级 分辨率高吞吐量，并将通过几个主要的进步，使x射线源和x射线 光学. 拟议的第一阶段6个月的项目是一个证明的原理演示的能力，x射线 聚焦光学元件拟议的第二阶段24个月的项目是开发一个完整的原型子， 细胞microXRF。

The ability to image elemental distribution and concentrations is increasingly critical to a variety of biomedical fields. Nearly all fundamental biological pathways have been found to require metal-binding proteins and trace elements, and an increasing number of pathologies are now linked – or hypothesized to be linked – to trace element dysregulation, including infertility and neurodegenerative diseases such as Alzheimer’s and Wilson’s. Moreover, novel pharmaceuticals comprising metallodrugs and nanoparticle-based treatments are on the rise, and an improved rational design approach to such drugs necessitates chemical imaging to determine the uptake and removal mechanisms of such drugs. Currently, laboratory approaches to elemental imaging are limited to around 10 micrometers, which does not allow for the critical subcellular elemental understanding that could potentiate breakthrough insights. The access of researchers to micron-scale resolution chemical imaging is limited to work performed at the synchrotron, which is a major bottleneck. In this small business innovation and research grant, we propose several major innovations to develop the first laboratory sub-cellular microXRF for the biomedical community, opening the path forward for achieving laboratory nanoXRF. The system will achieve micron-scale resolution at high throughput and will be enabled through several major advances to the x-ray source and x-ray optics. The proposed Phase I 6-month project is a proof-of-principle demonstration of the capabilities of the x-ray focusing optic component. The proposed Phase II 24-month project is to develop a complete prototype sub- cellular microXRF.