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个紧凑的，具有成本效益的高频，可调谐的二谐波回旋管，用于600 MHz的动态核极化（DNP）增强固态核磁共振（SSNMR）光谱。利用DNP，核磁共振实验中固有的小信号强度可以提高几个数量级。这种显著提高的总体灵敏度对于蛋白质、多肽或微rna的结构表征具有重要价值，这些蛋白质、多肽或微rna通常存在于复杂的生物相关混合物中，其浓度超出了传统核磁共振的灵敏度。在过去的十年中，这项技术已经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核磁共振信号强度，使模块化、紧凑、经济高效的基于陀螺的DNP系统适合商业部署。该系统的成功开发将使DNP增强核磁共振在结构生物学、制药研究和材料科学领域的快速扩散，这些领域是美国国立卫生研究院资助的许多项目感兴趣的领域。DNP需要连续波（CW），高功率（bbb20 w），高频太赫兹源，如回旋加速器，将电子的高热极化转移到周围的原子核。在第一阶段，我们建议开发一个395 GHz， 20 W的二次谐波回旋管，其调谐范围为1GHz，将受益于标准宽口径（89毫米）超导磁体，这将大大降低回旋管和整个系统的成本。回旋管将工作在395千兆赫，然而，该技术将适用于可用于生物固体的全系列宽口径（89毫米）光谱仪，从300兆赫到800兆赫。该系统将与瓦里安公司目前正在开发的低温魔角旋转ssmr探头相连接，使我们能够在第一阶段结束时演示一个功能性DNP系统。我们预计信号增强250英镑，对应于信号采集时间减少6万英镑。该系统将有几个新颖的功能，将允许客户简单地升级他们现有的核磁共振系统，从而节省他们在现有仪器上的投资。大的可调性（bbb1ghz）将使研究人员能够使用广泛的目前可用的极化剂，以及开发新的极化剂，而无需扫描线圈来改变核磁共振磁体的场。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。基于第一阶段获得的经验，我们将开发一个完全风冷的系统，消除水冷的需要。这将提高回旋管的可靠性，并将进一步降低系统成本。作为这个项目的结果，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，它在生物医学领域有多种用途，而不仅仅是核磁共振光谱，比如体内医学成像，癌症诊断和可能的治疗。

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.