High Sensitivity Solution DNP-NMR Probe with a Photonic Band Gap Resonator

描述（由申请人提供）：拟议的研究重点是开发用于动态核极化（DNP）增强溶液状态NMR光谱的NMR探针。使用DNP，NMR实验中固有的小信号强度可以增强几个数量级。这种显着增加的整体灵敏度将是非常有价值的分析应用核磁共振光谱以及生物大分子的结构表征。在过去的十年中，DNP已被证明是一种强大的方法，以增加高场，在世界各地的固态NMR（SSNMR）信号强度的实验室，最近，在适应DNP溶液状态NMR光谱已经取得了实质性进展。通过DNP（> 50）可获得的增强与可以从冷冻探针预期的灵敏度增益形成较大对比。虽然这两种技术的投资在类似的价格范围内（冷冻探针约30万美元，DNP系统约40万美元），但冷冻探针通常只能提供3-4倍的灵敏度增益。目前，在欧洲的大量努力是针对设计解决方案状态DNP探针的一个主要挑战是太赫兹谐振器的结合。这种谐振器是必要的，以尽量减少样品加热由于大太赫兹吸收的水介质。目前的设计使用金属谐振器，其与现有技术的高分辨率溶液状态NMR探针不兼容并且具有差的填充因子。我们提出了一种新的，介电谐振器，是兼容当前的高分辨率，溶液状态NMR探针设计。第一个原型将被设计为在300 MHz的NMR光谱仪频率下工作，但该技术预计将在600 MHz以上的NMR频率下工作。所提出的探针可以改装到现有的NMR光谱仪上，因此保留了对现有NMR平台的重大投资，使DNP增强的NMR光谱学的好处可以为更大的社区所用。随着诸如回旋管的高功率THz源的商业化，溶液状态DNP探针的开发对于商业部署来说是适时的。这种探针的成功开发将使DNP增强的溶液状态NMR光谱学在结构生物学，药物研究和分析化学中迅速扩散，这些都是美国国立卫生研究院资助的许多项目的兴趣。该提案的第一阶段致力于探头的电气和机械设计以及第一个原型的演示。作为该项目的结果，我们期望Bridge 12能够提供高分辨率的溶液状态DNP探针，该探针在分析化学和生物分子NMR光谱学中具有多种用途。 公共卫生相关性：拟议的研究重点是开发动态核极化（DNP）增强的溶液状态NMR光谱的NMR探针。DNP能够将NMR实验中观察到的固有小信号强度提高几个数量级，因此显著提高了该方法的整体灵敏度并缩短了采集时间。这对结构生物学、药物研究和分析化学非常感兴趣;这些领域对美国NIH资助的几个研究项目至关重要。所提出的探针技术甚至适用于当前可用的最高频率的光谱仪，并且可以在不改变当前NMR设施的布局的情况下安装，是平台非特异性的，并且可以被 对现有NMR系统进行改造。这将使DNP/NMR以合理的成本向更广泛的受众扩散。

DESCRIPTION (provided by applicant): 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.