SBIR-STTR Award

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 curing 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 requirement of either a specialized magnet or a gyrotron.

Public Health Relevance Statement:
A Novel Waveguide to Enable MAS-DNP-NMR in Standard-bore High-field Magnets Narrative Thousands of researchers are regularly using Nuclear Magnetic Resonance (NMR) techniques, with a majority of the applications driven by the need for structure and function determination in biological macromolecules. The advances developed under this project, in combination with several other advances under separate projects, will allow NMR laboratories to dramatically improve their sensitivity on solids, on a budget they will be able to afford, equipping biomedical researchers with superb new tools for the structure-function studies of membrane proteins and cellular membrane systems.

Project Terms:
Alzheimer's Disease; Amyloid; Amyloid Fibrils; Area; attenuation; Awareness; Binding; Biological; Biomedical Research; Budgets; Caliber; Cellular Membrane; Communication; Confined Spaces; cost; Country; Cryoelectron Microscopy; design; Dimensions; Electrons; experimental study; Frequencies; Funding; Future; HIV; imaging system; improved; in silico; Laboratories; macromolecule; Magic; Malignant Neoplasms; Membrane Proteins; meter; Methods; novel; Nuclear; Nuclear Magnetic Resonance; Pharmaceutical Preparations; Phase; Physiologic pulse; Play; Price; protein function; Proteins; Reporting; Research; Research Personnel; Resolution; restraint; Role; Scanning; Shapes; simulation; Small Business Innovation Research Grant; Solid; solid state; solid state nuclear magnetic resonance; Source; Spectrum Analysis; structural biology; Structure; System; Techniques; Time; tool; transmission process; Work

A Novel Waveguide to Enable MAS-DNP-NMR in Standard-bore High-field Magnets 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 ssNMRis crucial for both structural biology and biomedical research in general, for progress in curing 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 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 medical imaging methods.

Public Health Relevance Statement:
A Novel Waveguide to Enable MAS-DNP-NMR in Standard-bore High-field Magnets. Narrative: Thousands of researchers are regularly using Nuclear Magnetic Resonance (NMR) techniques, with a majority of the applications driven by the need for structure and function determination in biological macromolecules. The advances developed under this project, in combination with several other advances under separate projects, will allow NMR laboratories to dramatically improve their sensitivity on solids, on a budget they will be able to afford, equipping biomedical researchers with superb new tools for structure-function studies of membrane proteins and cellular membrane systems. The components developed under this project will also have major applications in ultra-broadband 6G communications equipment and THz medical imaging methods.

Project Terms:
<2019 novel corona virus><2019 novel coronavirus><2019-nCoV><6G Wi-Fi><6G Wireless Fidelity><6G communications>