The proposed research focuses on the development of a NMR probe for Dynamic Nuclear Polarization (DNP) enhanced solution-state NMR spectroscopy. With DNP, the inherently small signal intensities in an NMR experiment can be enhanced by several orders of magnitude. This significantly increased overall sensitivity will be of great value for analytical applications of NMR spectroscopy as well as the structural characterization of bio-macromolecules. In the last decade, DNP has proven to be a robust method to increase high-field, in solid-state NMR (SSNMR) signal intensities laboratories around the world and recently, substantial progress has been made in adapting DNP for solution-state NMR spectroscopy. The enhancements available through DNP (>50) are in Iarge contrast to the sensitivity gain that can be expected from a cryo-probe. While the investment for both technologies is in a similar price range (~ $300k for a cryo-probe, ~ $400k for a DNP system), cryo-probes typically deliver only a factor of 3-4 in sensitivity gain. Currently, substantial effort in Europe is directed towards designing solution-state DNP probes with one major challenge being the incorporation of a THz resonator. This resonator is required to minimize sample heating due to the large THz absorption of aqueous media. Current designs are using metallic resonators, which are incompatible with state-of-the-art high-resolution solution- state NMR probes and have a poor filling factor. We propose a novel, dielectric resonator that is compatible with current high-resolution, solution-state NMR probe designs. The first prototype will be designed to operate at an NMR spectrometer frequency of 300 MHz but the technology is expected to work at NMR frequencies even above 600 MHz. The proposed probe can be retrofitted to existing NMR spectrometers, therefore preserving the significant investments in existing NMR platforms, making the benefits of DNP-enhanced NMR spectroscopy available to a larger community. With high-power THz sources such as gyrotron commercially available, the development of a solution-state DNP probe is well timed for commercial deployment. The successful development of this probe will enable the rapid proliferation of DNP-enhanced solution-state NMR spectroscopy for structural biology, pharmaceutical research and analytical chemistry, which are of interest in many projects funded by the U.S. National Institutes of Health. Phase I of the proposal is dedicated to the electrical and mechanical design of the probe and the demonstration of a first prototype. As a result of this project, we expect Bridge12 to deliver a high-resolution solution-state DNP probe, which has a variety of uses in analytical chemistry and bio-molecular NMR spectroscopy.

Public Health Relevance

The proposed research focuses on the development of a NMR probe for Dynamic Nuclear Polarization (DNP) enhanced solution-state NMR spectroscopy. DNP has the capability to enhance the inherently small signal intensities observed in an NMR experiment by several orders of magnitude, and therefore dramatically increase the overall sensitivity of the method and reduce the acquisition time. This is of great interest for structural biology, pharmaceutical research and analytical chemistry;areas that are of vital for several research projects funded by the U.S. NIH. The proposed probe technology is applicable to even to the highest frequency spectrometers currently available and can be installed without altering the layout of current NMR facilities, is platform-nonspecific and can be retro-fitted to existing NMR systems. This will enable the proliferation of DNP/NMR to a wider audience at a reasonable cost.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
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Special Emphasis Panel (ZRG1-IMST-N (11))
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Wehrle, Janna P
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Bridge 12 Technologies, Inc.
United States
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