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

NIH RePORTER · NIH · R44 · $848,143 · view on reporter.nih.gov ↗

Abstract

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.

Key facts

NIH application ID
10760278
Project number
5R44GM139468-03
Recipient
DOTY SCIENTIFIC, INC.
Principal Investigator
Francis DAVID Doty
Activity code
R44
Funding institute
NIH
Fiscal year
2024
Award amount
$848,143
Award type
5
Project period
2020-08-01 → 2025-12-31