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.

元素分布和浓度成像的能力对于各种生物医学越来越重要 几乎所有基本的生物途径都被发现需要金属结合蛋白和痕量。 元素和越来越多的病理学现在被联系起来——或者率先联系起来——追踪 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，包括金属药物和纳米颗粒治疗在内的新型药物正在兴起， 此类药物的改进合理设计方法需要化学成像来确定 此类药物的吸收和清除机制。 目前，实验室的元素成像方法仅限于 10 微米左右，这并不能解决问题。 允许对关键的亚细胞元素进行理解，从而增强突破性的见解。 研究人员对微米级分辨率化学成像的访问仅限于在 同步加速器是一个主要瓶颈，在这项小型企业创新和研究资助中，我们提出了这一建议。 开发第一个用于生物医学的实验室亚细胞 microXRF 的多项重大创新 社区，为实现实验室纳米XRF开辟了道路，该系统将实现微米级。 高通量分辨率，并将通过 X 射线源和 X 射线的几项重大进步来实现 光学。 拟议的为期 6 个月的第一阶段项目是 X 射线功能的原理验证演示 拟议的第二阶段24个月的项目是开发一个完整的原型子。 细胞微XRF。