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用于600 MHz动态核极化(DNP)增强型固态核磁共振(SS核磁共振)谱的紧凑、成本效益高的高频可调二次谐波回旋管。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。这种显著提高的总体灵敏度将对蛋白质、多肽或微小RNA的结构表征具有重要价值，这些蛋白质、多肽或微小RNA通常存在于复杂的生物相关混合物中，其浓度高于常规核磁共振的灵敏度。在过去的十年中，这项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提高核磁共振的信号强度，使模块化、紧凑、成本效益高的基于回旋管的DNP系统非常适合商业部署。该系统的成功开发将使DNP增强型核磁共振在结构生物学、制药研究和材料科学中迅速普及，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。DNP需要一个连续波(CW)、高功率(&gt；20W)、高频太赫兹源(如回旋加速器)来将电子的高热极化传输到周围的原子核。在第一阶段，我们建议开发一台395 GHz、20W、调谐范围为1 GHz的二次谐波回旋管，该回旋管将受益于标准的大口径(89 Mm)超导磁体，从而显著降低回旋管的成本，从而降低整个系统的成本。回旋管将工作在395 GHz，然而，该技术将适用于可用于生物固体的全范围大口径(毫米)光谱仪，从300 MHz到800 MHz。该系统将与瓦里安公司目前正在开发的低温魔角旋转SS核磁共振探头对接，使我们能够在第一阶段结束前演示功能强大的DNP系统。我们预计&gt；250的信号增强，对应于&gt；60,000的信号采集时间的缩短。该系统将具有几个新的功能，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(&gt；1 GHz)将使研究人员能够使用目前可用的各种偏振剂，以及开发新的偏振剂，而不需要扫描线圈来改变核磁共振磁铁的磁场。在项目第二阶段，我们将进一步评估整个回旋加速器系统，解决第一阶段发现的问题。根据第一阶段获得的经验，我们将开发一种完全风冷的系统，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成本。作为该项目的结果，我们预计Bridge 12将提供一种紧凑、高功率、高频和可调谐的回旋管，该回旋管在核磁共振光谱以外的生物医学领域具有多种用途，例如体内医学成像，以及用于癌症诊断和可能的治疗。 与公众健康相关：拟议的研究旨在设计和演示一种紧凑、经济高效的高频可调二次谐波回旋加速器，用于600 MHz的动态核极化(DNP)增强型固态核磁共振(SS核磁共振)谱。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、制药研究和材料科学都很有兴趣，这些领域都是由美国国立卫生研究院资助的研究领域。建议的系统可以扩展到与高达800 MHz的SS核磁共振系统相匹配，并且可以在不改变现有核磁共振设施布局的情况下安装。它是不特定于平台的，支持现有SS核磁共振系统的升级(升级)。这将使固态DNP/核磁共振能够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、可调的太赫兹回旋源，它也可以用于体内成像，以诊断癌症，并可能用于癌症的治疗。

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.