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

一种亚细胞微 X 射线荧光系统，用于在生物组织中快速采集元素成像

• 批准号: 10019577
• 负责人: Wenbing Yun
• 金额: $ 63.22万
• 依托单位: SIGRAY, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10019577
• 关键词: Alzheimer' s Disease; Arthritis; Automobile Driving; Binding Proteins; Biological; Biological Process; Brain; Cells; Characteristics; Chemicals; Communities; Detection; Development; Disease; Electrons; Elements; Excision; Fluorescence; Follow-Up Studies; Freeze Drying; Goals; Gold; HIV; Human; Huntington Disease; Image; Imaging Techniques; Infertility; Laboratories; Link; Measures; Metals; Neurodegenerative Disorders; Optics; Organ; Parkinson Disease; Pathology; Pathway interactions; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Play; Population; Process; Research; Research Personnel; Resolution; Roentgen Rays; Role; Schizophrenia; Serum; Signal Transduction; Small Business Innovation Research Grant; Solid; Source; Specimen; Spectrum Analysis; Speed; Spottings; Synchrotrons; System; Techniques; Therapeutic; Time; Tissues; Trace Elements; Work; absorption; anti-cancer; base; biological systems; commercialization; design; improved; in vivo; innovation; insight; interest; nanoparticle; nanoparticle drug; novel; penis; prototype; tumor; uptake

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.

图像元素分布和浓度的能力对多种生物医学越来越重要 字段。几乎所有基本的生物学途径都需要金属结合蛋白和痕迹 元素和越来越多的病理已链接（或假设是链接的），以追踪 元素失调，包括不育和神经退行性疾病，例如阿尔茨海默氏症和威尔逊。 此外，新型药物完成金属果和基于纳米颗粒的疗法正在上升， 并改进了此类药物必要的化学成像的理性设计方法，以确定 此类药物的摄取和去除机制。 当前，实验室的元素成像方法仅限于10微米，而不是 允许具有可能突破性见解的关键亚细胞元素理解。这 研究人员进入微米级分辨率化学成像仅限于在 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赠款中，我们建议 为生物医学开发第一个实验室亚细胞微XRF的几项主要创新 社区，为实现实验室NanoxRF的前进开辟了道路。该系统将实现微米级 高吞吐量的分辨率将通过X射线源和X射线的几个重大进步启用 光学。 拟议的I阶段6个月项目是X射线功能的原则证明 聚焦视觉组件。拟议的II期24个月项目是开发一个完整的原型子 - 细胞Microxrf。