Compact System for Dynamic Nuclear Polarization Enhanced 600 MHz Solid-State NMR

描述（由申请人提供）：拟议的研究旨在设计和演示一种紧凑的，具有成本效益的高频，可调二次谐波回旋管，用于600 MHz的动态核极化（DNP）增强固态核磁共振（SSNMR）光谱。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蛋白质，肽，或微RNA的结构表征，通常存在于复杂的生物相关的混合物中的浓度超过传统的NMR的灵敏度。在过去的十年中，该技术已被证明是一种强大的方法，可以在世界各地的实验室中增加NMR的信号强度，使模块化，紧凑，具有成本效益的基于陀螺仪的DNP系统非常适合商业部署。该系统的成功开发将使DNP增强NMR在结构生物学、药物研究和材料科学中的快速扩散成为可能，这些都是美国国立卫生研究院资助的许多项目所感兴趣的。DNP需要连续波（CW）、高功率（> 20 W）、高频太赫兹源（如回旋管）将电子的高热极化传递到周围的原子核。在第一阶段，我们建议开发一个395 GHz，20 W的第二谐波回旋管与1 GHz的调谐范围，将受益于一个标准的宽口径（89毫米）超导磁体，显着降低成本的回旋管，从而整个系统。回旋管将在395 GHz下工作，然而，该技术将适用于生物固体的全系列宽口径（89 mm）光谱仪，从300 MHz到800 MHz。该系统将连接到Varian公司目前正在开发的低温魔角自旋SSNMR探头，使我们能够在第一阶段结束时演示功能性DNP系统。我们预期信号增强> 250，对应于信号采集时间减少> 60，000。该系统将有几个新的功能，将允许客户简单地升级其现有的核磁共振系统，从而节省他们在现有仪器的投资。大的可调谐性（> 1 GHz）将使研究人员能够使用广泛的现有极化剂，以及开发新的极化剂，而不需要扫描线圈来改变NMR磁体的磁场。在项目的第二阶段，我们将进一步评估整个回旋管系统，解决第一阶段发现的问题。根据第一阶段取得的经验，我们将开发一种完全空气冷却的系统，消除对水冷却的需要。这将提高回旋管的可靠性，并将进一步降低系统的成本。作为该项目的结果，我们期望Bridge 12能够提供一种紧凑，高功率，高频和可调谐的回旋管，它在NMR光谱学之外的生物医学领域具有多种用途，例如体内医学成像和癌症诊断以及可能的治疗。 公共卫生相关性：所提出的研究是针对设计和展示一个紧凑的，具有成本效益的高频，可调谐的二次谐波回旋管的动态核极化（DNP）增强固态核磁共振（SSNMR）光谱在600 MHz。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、药物研究和材料科学都有很大的意义;这些领域对美国国立卫生研究院资助的研究有重大意义。拟议的系统可以缩放，以匹配高达800 MHz的SSNMR系统，并且可以在不改变当前NMR设施布局的情况下安装。它是平台非特定的，使现有的SSNMR系统的升级（改造）。这将使固态DNP/NMR以合理的成本向更广泛的受众扩散。该系统的核心将是一个紧凑的、可调谐的太赫兹回旋管源，它也可用于癌症诊断和治疗的体内成像。

DESCRIPTION (provided by applicant): The proposed research is directed at designing and demonstrating a compact, cost-effective high-frequency, tunable 2nd-harmonic gyrotron for Dynamic Nuclear Polarization (DNP) enhanced solid-state Nuclear Magnetic Resonance (SSNMR) spectroscopy at 600 MHz. With DNP, the inherently small signal intensities in a NMR experiment can be enhanced by several orders of magnitude. This significantly increased overall sensitivity will be of great value for the structural characterization of proteins, peptides, or micro RNAs that normally exist in complex biologically-relevant mixtures at concentrations beyond the sensitivity of conventional NMR. In the last decade, this technique has proven to be a robust method to increase signal intensities in NMR in laboratories around the world, making a modular, compact, cost-effective gyrotron-based DNP system well-timed for commercial deployment. The successful development of this system will enable the rapid proliferation of DNP enhanced NMR for structural biology, pharmaceutical research and material science, which are of interest in many projects funded by the U.S. National Institutes of Health. DNP requires a continuous-wave (CW), high-power (> 20W), high-frequency terahertz source such as a gyrotron to transfer the high thermal polarization of the electron to the surrounding nuclei. In phase I we propose to develop a 395 GHz, 20 W 2nd harmonic gyrotron with 1GHz tuning range that will benefit from a standard wide-bore (89 mm) superconducting magnet, a significant cost-reduction for the gyrotron and thus the overall system. The gyrotron will operate at 395 GHz, however, the technology will be applicable for the full range of wide-bore (89 mm) spectrometers available for biosolids, from 300 MHz to 800 MHz. The system will be interfaced to a cryogenic Magic Angle Spinning SSNMR probe curently under development at Varian Incorporated, alowing us to demonstrate a functional DNP system by the end of Phase I. We expect signal enhancement of > 250, corresponding to a time reduction for signal acquisition of > 60,000. The system will have several novel features that will allow customers to simply upgrade their existing NMR systems, thus conserving their investment in existing instruments. The large tunability (> 1 GHz) will enable researchers to use a broad range of currently available polarizing agents, as well as develop new ones without the need for a sweep coil to change the field of the NMR magnet. In phase II of the project we will further evaluate the overall gyrotron system, addressing issues identified during Phase I. Based on the experience gained in phase I, we will develop a completely air cooled system eliminating the need for water-cooling. This will improve the reliability of the gyrotron and will further reduce the cost of the system. As a result of this project, we expect Bridge 12 to make available a compact, high-power, high-frequency, and tunable gyrotron, which has a variety of uses in biomedical areas beyond NMR spectroscopy such as in-vivo medical imaging and for diagnosis of cancer and possibly its treatment. PUBLIC HEALTH RELEVANCE: The proposed research is directed at designing and demonstrating a compact, cost-effective high- frequency, tunable 2nd-harmonic gyrotron for Dynamic Nuclear Polarization (DNP) enhanced solid-state Nuclear Magnetic Resonance (SSNMR) spectroscopy at 600 MHz. 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 high interest for structural biology, pharmaceutical research and material science; areas that are of significant interest to research funded by the U.S. National Institutes of Health. The proposed system can be scaled to match SSNMR systems up to 800 MHz and can be installed without altering the layout of current NMR facilities. It is platform-nonspecific, enabling the upgrade (retro-fit) of existing SSNMR systems. This will enable the proliferation of solid-state DNP/NMR to a wider audience at a reasonable cost. The heart of the system will be a compact, tunable terahertz gyrotron source, which could also be used for in-vivo imaging for diagnosis of cancer and possibly its therapy.