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来说越来越重要 菲尔兹。几乎所有的基本生物途径都被发现需要金属结合蛋白和示踪 元素，越来越多的病理现在被关联-或假设被关联-与痕迹 元素失调，包括不孕症和神经退行性疾病，如阿尔茨海默氏症和威尔逊氏症。 此外，包括金属药物和基于纳米颗粒的治疗的新型药物正在增加， 而一种改进的合理设计这种药物的方法需要化学成像来确定 这类药物的摄取和清除机制。 目前，实验室的元素成像方法被限制在10微米左右，这不是 考虑到关键的亚细胞元素理解，这可能会增强突破性的见解。这个 研究人员获得微米级分辨率化学成像的机会仅限于在 同步加速器，这是一个主要的瓶颈。在这项小型企业创新和研究基金中，我们建议 开发首个用于生物医学的实验室亚细胞微X射线荧光的几项重大创新 社区，为实现实验室纳米XRF开辟了道路。该系统将达到微米级 在高通量下的分辨率，并将通过对x射线源和x射线的几项重大改进来实现 光学。 拟议的第一阶段为期6个月的项目是对x射线能力的原则证明演示。 聚焦光学组件。拟议的第二阶段为期24个月的项目是开发一个完整的原型分部 细胞微X射线荧光光谱仪。

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.