DOTY SCIENTIFIC, INC. — Department of Health and Human Services SBIR Phase I: NIA

Description

A Novel Millimeter wave mmw DNP EPR Front end Compatible with Versatile High field NMR Probes Abstract There has been explosive growth in interest in Dynamic Nuclear Polarization DNP with Magic Angle Spinning MAS over the past five years because it has demonstrated S N gains exceeding two orders of magnitude at K compared to conventional MAS NMR and non spinning NMR of biological macromolecules in their supramolecular assemblies under ambient conditions The reduction in signal acquisition time up to four orders is promising for a wide range of applications and in particular structure determination and function elucidation of biological macromolecules Despite this enormous potential benefit the adaptation rate of DNP will be severely limited by its very high price tag currently $ M largely because of the expensive gyrotron that has been required and because of the need for a special NMR magnet with superconducting sweep coils as the bandwidth of the gyrotron is very narrow Our preliminary simulations of a novel millimeter wave mmw DNP cavity that is compatible with a new MAS spinner design have shown the potential for achieving the needed electron spin saturation with up to two orders of magnitude lower microwave power than with existing MAS DNP probes for samples of similar volume L and other conditions With such an advance in mmw cavity design along with the order of magnitude progress in broad band solid state InP mmw power amplifiers seen over the past five years amplifiers now up to GHz it can become possible to eliminate both the gyrotron and need for a special NMR magnet with superconducting sweep coils even at NMR frequencies to MHz GHz EPR These transformational advances can permit an enormous reduction in the cost of bringing MAS DNP into an ssNMR laboratory thereby making it possible for virtually all current NMR groups to begin developing and applying powerful new methods to structure determination and function elucidation of insoluble rigid proteins and other macromolecules that are key to progress in developing cures for Alzheimer s Disease and cancer However in addition to the need for efficient MAS DNP mmw spinner cavities a novel low cost EPR mmw front end bridge is critically needed so that EPR experiments can first be carried out within the high field NMR magnet on the prepared sample to facilitate essential calibration and optimization for the subsequent MAS DNP experiments Unfortunately the needed mmw front end hardware is not available and a radically new approach appears necessary if DNP is to become widely implemented This Phase I would design develop and characterize a unique microelectronics mmw circuit for initial demonstration during the Phase II at GHz MHz that will be the basis for an add on DNP EPR front end accessory eventually up to GHz for existing high field ssNMR spectrometers Simulations analysis and hardware tests will establish the potential for an order of magnitude reduction in system cost and two orders of magnitude increase in EPR sensitivity compared to previously published approaches to high field EPR Moreover the novel approach will be compatible with H X Y MAS DNP probes of commercially viable designs A Novel Millimeter wave mmw DNP EPR Front end Compatible with Versatile High field NMR Probes 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 will allow almost every NMR laboratory to begin applying Dynamic Nuclear Polarization DNP to both solids and liquids on a budget they will be able to afford equipping biomedical researchers with superb new tools for the structure function studies of membrane proteins gaining information that is essential in developing cures for Alzheimer s Disease and cancer