Doty Scientific Inc

High-order Cavities for Enabling High-field Mas-dnp-nmr With Low-cost THZ Sources - High-order Cavities for Enabling High-field Mas-dnp-nmr With Low-cost THZ Sources Abstract Recently the First Atomic-resolution Structures of the ASS40 and ASS42 Amyloid Fibrils That Play an Important Role in Alzheimer’s Disease (AD) Were Solved by a Combination of Methods That Relied Critically on Solid-state NMR (ssnmr). 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 Microscopy (STEM) and Other Methods Provided Much Useful Information and Low-resolution Structures, Recent Advances in Mas-nmr Methods Provided 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 Advances for Ssnmr Is Crucial for Both Structural Biology and Biomedical Research in General, for Progress in Addressing Alzheimer’s Disease, Novel Viruses, Cancer, Arthritis, and Other Inflammasome-related Diseases, Particularly for Providing Regio-specific Drug Binding Information Enabling Detailing of the Mechanism of Action for Effective Drugs. High-field (>11 T) Mas-dnp Systems Thus Far Have All Required the High Microwave Power Only Available From Gyrotrons. Because of Their Narrow Bandwidth, They Then Require an NMR Magnet With Superconducting Sweep Coils and Thus Directly and Indirectly Add $1.5-3M to the System Cost. Moreover, the DNP Methods Are Limited by the Poor Frequency Agility of Gyrotrons, and Many Crowded NMR Laboratories Simply Do Not Have Space to Accommodate a Gyrotron or the Funds to Acquire One. While a Recent Advance in a Commercially Available 1.3-MM Mas-dnp Probe Showed Improved Microwave Efficiency at 9.4 T (400 MHZ/263 GHZ), Our Detailed Simulations Show That Still Only 2-9% of the Incident Micro- Wave Power Is Dissipated Within the Lossy Sample. This Suggests There Is Room for Another Order of Magnitude Improvement in Microwave Efficiency, and Our Preliminary Simulations of a Novel High-order Microwave Cavity Compatible With a Novel Mas Spinner Design Further Support This Goal. This Proposed Phase I Sbir Will Carry Out in Silico Evaluations of Novel Fast-mas Spinner Designs With Integral High-order Microwave Cavities That Promise Order-of-magnitude Increases in Microwave Efficiency at Frequencies in the 195-528 GHZ Range (as Needed for NMR at 7-18.8 T). Experimental Evaluations of Novel Cavity- Mas-dnp Modules Will Be Carried Out Using a Solid-state Source on the Bench and in a Triple-resonance 500MHZ/328GHZ 1.3-MM Mas-dnp Probe at 11.7 T. 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.