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)增强的溶液状态核磁共振光谱学的核磁共振探针。有了DNP，核磁共振实验中固有的小信号强度可以增强几个数量级。这一显著提高的总体灵敏度将对核磁共振波谱的分析应用以及生物大分子的结构表征具有重要价值。在过去的十年中，DNP已被证明是在世界各地的固态核磁共振(SSNMR)实验室中增强高场信号强度的一种强有力的方法，最近，在将DNP应用于溶液状态核磁共振光谱方面取得了实质性进展。通过DNP(&gt；50)可获得的增强与低温探头可预期的灵敏度提高形成鲜明对比。虽然这两种技术的投资在类似的价格范围内(低温探头约30万美元，DNP系统约40万美元)，但低温探头通常只能提供3-4倍的灵敏度收益。目前，欧洲正致力于设计溶液状态的DNP探测器，其中一个主要挑战是引入THz谐振器。由于水介质具有很大的太赫兹吸收，因此需要这种谐振器来最大限度地减少样品加热。目前的设计使用的是金属谐振器，这与最先进的高分辨率溶液状态核磁共振探头不兼容，而且填充系数很低。我们提出了一种新颖的介质谐振器，它与目前的高分辨率溶液状态核磁共振探头设计兼容。第一个原型将被设计为在300 MHz的核磁共振光谱仪频率下工作，但这项技术预计将在600 MHz以上的核磁共振频率下工作。建议的探头可以改装到现有的核磁共振光谱仪上，因此保留了对现有核磁共振平台的重大投资，使更大的社区能够享受到DNP增强的核磁共振光谱的好处。随着回旋管等高功率太赫兹光源的商用，溶液状态DNP探测器的开发正处于商业部署的有利时机。该探头的成功开发将使DNP增强型溶液状态核磁共振波谱在结构生物学、药物研究和分析化学中的快速普及，这些都是美国国立卫生研究院资助的许多项目中感兴趣的。该提案的第一阶段专门用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，我们预计Bridge12将提供一种高分辨率的溶液状态DNP探测器，该探测器在分析化学和生物分子核磁共振光谱中有多种用途。 公共卫生相关性：拟议的研究重点是开发用于动态核极化(DNP)增强的溶液状态核磁共振波谱的核磁共振探针。DNP能够将在核磁共振实验中观察到的固有的小信号强度提高几个数量级，从而显著提高方法的总体灵敏度并缩短采集时间。这对结构生物学、药物研究和分析化学非常感兴趣，这些领域对美国国立卫生研究院资助的几个研究项目至关重要。建议的探测技术甚至适用于目前可用的最高频率光谱仪，可以在不改变现有核磁共振设施布局的情况下安装，是不特定于平台的，可以 改装到现有的核磁共振系统。这将使DNP/核磁共振能够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.