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

基本信息

批准号：
10602643
负责人：
Francis DAVID Doty
金额：
$ 86.07万
依托单位：
DOTY SCIENTIFIC, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10602643
关键词：
2019-nCoV 6G Wi-Fi Alzheimer&apos s Disease Amyloid Fibrils Amyloid beta-42 Amyloid beta-Protein Area Awareness Binding Biological Biomedical Research Budgets Cellular Membrane Communication Confined Spaces Country Cryoelectron Microscopy Data Development Diameter Engineering Equipment Frequencies Funding Future HIV High temperature of physical object Laboratories Magic Malignant Neoplasms Medical Imaging Membrane Proteins Methods Nuclear Nuclear Magnetic Resonance Optics Pharmaceutical Preparations Phase Physiologic pulse Play Price Proteins Publishing Research Research Personnel Resolution Role Satellite Communications Scanning Tunneling Microscopy Shapes Signal Transduction Small Business Innovation Research Grant Solid Source Spectrum Analysis Structure System Techniques Technology Temperature Testing Time Work astrophysics attenuation cold temperature cost design imaging modality imaging system improved invention macromolecule manufacture manufacturing cost meter next generation novel operation photonics restraint solid state solid state nuclear magnetic resonance structural biology tool transmission process waveguide

项目摘要

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 crucial role in Alzheimer’s Disease (AD). Key to that structure determination was a technique denoted as dynamic nu- clear polarization (DNP) with magic angle spinning (MAS). While Cryo EM, scanning tunneling electron micros- copy (STEM) and other methods provided useful information, recent advances in MAS-NMR methods provided essential restraints and additional crucial information. Hence, developing transformational advances for ssNMR is crucial for both structural biology and biomedical research in general, for progress in curing Alzheimer’s Dis- ease 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 largely because known de- signs 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 cost for MAS- DNP, which has put it out of reach to all but a few premiere laboratories. The Phase-I of this effort demonstrated what we believe can fairly be described as the most significant advance in waveguides for the 40-1500 GHz range in half a century – since the invention of corrugated waveguides. Their attenuation is two orders of mag- nitude below that of prior small waveguides at 400 GHz and comparable to that of the very expensive corrugated waveguides where the diameter is tightly constrained. Manufacturing costs are expected to be well over an order of magnitude below those of corrugated waveguides, and they can readily be made at diameters small enough to make MAS-DNP probes practical in existing NB high-field magnets. This proposed Phase II effort continues the development of our revolutionary broad-band Laminate-Lined Wave- Guides (LLWGs) and tapered transitions, for use over the 40-1500 GHz range, as needed for NMR at 1.5-55 T. It is expected that this advance, in combination with several other technological advances being pursued in other projects, will enable DNP to be added to existing ssNMR high-field systems without the requirement of either a specialized magnet or a gyrotron. This Phase-II effort further proposes to demonstrate a 500 MHz NB HXY MAS- DNP probe operating below 50 K utilizing LLWGs. The LLWG developments will also have major applications in ultra-broadband 6G communications equipment, next-gen satellite communications, astrophysics, and THz med-ical imaging methods.

一种新型波导，可在标准孔径高场磁体中实现 MAS-DNP-NMR 抽象的经过近二十年的研究，最近证明了固态核磁共振 (ssNMR) 的至关重要性经过不懈的努力，产生了 A?40 和 A?42 淀粉样原纤维的第一个原子分辨率结构，这些结构发挥着至关重要的作用确定结构的关键是一种称为动态核的技术。透明偏振 (DNP) 和魔角旋转 (MAS)，而冷冻电镜、扫描隧道电子显微镜。复制（STEM）和其他方法提供了有用的信息，提供了 MAS-NMR 方法的最新进展因此，开发 ssNMR 的变革性进展。一般来说，对于结构生物学和生物医学研究以及治疗阿尔茨海默病的进展至关重要缓解和癌症，并提供区域特异性药物结合信息，从而能够详细了解该机制有效药物的作用。迄今为止，MAS-DNP 系统都需要专门的宽孔 (WB) 磁体，主要是因为已知的去波导与太赫兹传输兼容的迹象以及各种相关问题不容小觑足以用于标准孔径（SB，也称为窄孔径，NB）磁体的探头。 WB 磁体和所需的波纹太赫兹波导构成了 MAS- 的高成本的很大一部分。 DNP，除了少数顶级实验室之外，其他所有实验室都无法实现这一目标。这一努力的第一阶段已得到证明。我们认为这可以说是 40-1500 GHz 波导领域最重大的进步自从波纹波导发明以来，它们的衰减是两个数量级。其频率低于 400 GHz 时现有小型波导，与非常昂贵的波纹管相当直径受到严格限制的波导的制造成本预计将远远超过订单。其数量级低于波纹波导，并且可以很容易地制成足够小的直径使 MAS-DNP 探头在现有的 NB 高场磁体中实用。这项拟议的第二阶段工作继续开发我们革命性的宽带层压板波状导轨 (LLWG) 和锥形过渡，适用于 40-1500 GHz 范围，根据 1.5-55 T NMR 的需要。预计这一进步与其他领域正在追求的其他几项技术进步相结合项目，将使 DNP 能够添加到现有的 ssNMR 高场系统中，而不需要该第二阶段工作进一步建议展示 500 MHz NB HXY MAS-。利用 LLWG 运行在 50 K 以下的 DNP 探针 LLWG 的开发也将在以下领域有主要应用。超宽带6G通信设备、下一代卫星通信、天体物理学和太赫兹医学成像方法。