A Novel Waveguide to Enable MAS-DNP-NMR in Standard-bore High-field Magnets

一种新型波导，可在标准孔径高场磁体中实现 MAS-DNP-NMR

• 批准号: 10081009
• 负责人: Francis DAVID Doty
• 金额: $ 29.72万
• 依托单位: DOTY SCIENTIFIC, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2021-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10081009
• 关键词: Alzheimer' s Disease; Amyloid; Amyloid Fibrils; Area; Awareness; Binding; Biological; Biomedical Research; Budgets; Caliber; Cellular Membrane; Communication; Confined Spaces; Country; Cryoelectron Microscopy; Dimensions; Electrons; Frequencies; Funding; Future; HIV; Laboratories; Magic; Malignant Neoplasms; Membrane Proteins; Methods; Nuclear; Nuclear Magnetic Resonance; Pharmaceutical Preparations; Phase; Physiologic pulse; Play; Price; Proteins; Reporting; Research; Research Personnel; Resolution; Role; Scanning; Shapes; Small Business Innovation Research Grant; Solid; Source; Spectrum Analysis; Structure; System; Techniques; Time; Work; attenuation; cost; design; experimental study; imaging system; improved; in silico; macromolecule; meter; novel; protein function; restraint; simulation; solid state; solid state nuclear magnetic resonance; structural biology; tool; transmission process

A Novel Waveguide to Enable MAS-DNP-NMR in Standard-bore High-field Magnets Abstract The critical importance of solid-state NMR (ssNMR) was recently demonstrated by, after nearly two decades of intense efforts, yielding the first atomic-resolution structures of the A40 and A42 amyloid fibrils that play a cru- cial role in Alzheimer’s Disease (AD). Key to that structure determination was a technique denoted as dynamic nuclear polarization (DNP) with magic angle spinning (MAS). While Cryo EM, scanning tunneling electron mi- croscopy (STEM) and other methods provided useful information, recent advances in MAS-NMR methods pro- vided essential restraints and additional crucial information, including sidechain dynamics important in protein functions and in understanding of myriad mechanisms of their action. Hence, developing transformational ad- vances for ssNMR is crucial for both structural biology and biomedical research in general, for progress in cur- ing Alzheimer’s Disease and cancer, and for providing regio-specific drug binding information enabling detailing of the mechanism of action for effective drugs. MAS-DNP systems thus far have all required specialized wide-bore (WB) magnets because known designs of waveguides compatible with THz transmission and the various relevant issues cannot be made small enough to work in probes for use in standard-bore (SB, also called narrow-bore, NB) magnets. The specialized WB magnets and the required corrugated THz waveguides constitute a large portion of the high system cost for MAS-DNP, which has put it out of reach to all but a few premiere laboratories. This proposed Phase I SBIR will show feasibility of a revolutionary broad-band multi-mode waveguide for use in the 85-1000 GHz range (as needed for NMR at 3-35 T) that can easily be manufactured at diameters small enough to make MAS-DNP probes practical in existing NB high-field magnets. Attenuation is predicted to be two orders of magnitude be- low that of fundamental-mode waveguides at 400 GHz and even lower than that of the very expensive corru- gated over-moded waveguides for a wide range of applications. It is expected that this advance, in combination with several other technological advances being pursued in other projects, will eventually enable DNP to be added to existing ssNMR high-field systems without the re- quirement of either a specialized magnet or a gyrotron.

一种新型的波导，可在标准孔高磁场中启用MAS-DNP-NMR 抽象的 近二十年后，最近证明了固态NMR（SSNMR）的关键重要性 激烈的努力，产生了A40和A42淀粉样蛋白纤维的第一个原子分辨率结构 在阿尔茨海默氏病（AD）中的作用。该结构确定的关键是一种表示动态的技术 具有魔法角度旋转（MAS）的核极化（DNP）。在冷冻em时，扫描隧道电子 crscopy（STEM）和其他方法提供了有用的信息，MAS-NMR方法的最新进展 涉及的基本约束和其他关键信息，包括在蛋白质中重要的侧链动力学 功能和理解其行动的无数机制。因此，发展了变革性的广告 SSNMR的Vances对于结构生物学和一般的生物医学研究至关重要 阿尔茨海默氏病和癌症，以及提供区域特异性药物结合信息，以实现细节 有效药物的作用机理。 到目前为止，MAS-DNP系统都需要专业的宽孔（WB）磁铁 波导与THZ传输兼容，各种相关问题不能足够小 用于用于用于标准孔（SB，也称为窄孔，NB）的问题。专业WB 磁铁和所需的瓦楞THZ波导构成了高系统成本的很大一部分 MAS-DNP，除了几个首屈一指的实验室外，它都无法触及。这个提议的阶段我将 显示在85-1000 GHz范围内使用的革命性宽带多模式波导的可行性（AS NMR在3-35 t中需要，可以在直径的小时轻松制造以使MAS-DNP制造 现有的NB高场磁铁中实用的问题。预计衰减为两个数量级。 低于400 GHz的基本模式波导的低，甚至低于非常昂贵的Corru- 用于广泛应用的门控过多的波导。 预计这一进步结合了其他几项技术进步 其他项目最终将使DNP能够添加到现有的SSNMR高场系统中，而无需重新 专用磁铁或陀螺仪的要求。