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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：
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
项目类别：
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&apos 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

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 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.

在标准口径高场磁体中实现MAS-DNP-NMR的新型波导