Advanced Instrumentation for Dynamic Nuclear Polarization NMR Research

拟议的研究重点是动态核极化（DNP）领域的基本进展 NMR将使这种强大的技术更容易获得和有用的国家和国际 生物医学研究社区。在DNP NMR中，使用高频微波源来照射电子， 核跃迁，从而将电子自旋库中的高自旋极化转移到核中， 自旋系统通过超精细和偶极相互作用。由此产生的NMR信号的增强已经被证明是有效的。 证明超过400倍，因此DNP NMR现在被认为是NMR的重大进展 谱激发电子自旋系统所需的微波频率为太赫兹 频率范围：400 MHz、600 MHz和800 MHz 1H频率分别为263 GHz、395 GHz和527 GHz。到 迄今为止，用于魔角旋转（MAS）NMR实验的DNP依赖于具有连续的回旋管振荡器， 功率输出几十瓦。回旋管现在已经可以在市场上买到，并且已经有40多个这样的系统 在过去的十年里，世界各地都在安装。然而，用于DNP的回旋管非常昂贵，超过60万美元， NIH共享工具赠款的费用限制。回旋管也相对较大，从而产生了附加的问题， 对实验室空间和选址的需求。拟议研究的主旨是从根本上减少所需的 DNP/NMR的功率水平下降到更小和更便宜的来源，包括 太赫兹速调管和固态源。这将通过大幅改善电力耦合来实现， 样品，并通过显着提高传输线的传输效率。我们建议这些 具体研究活动：1.）我们将使用最先进的电磁学模拟来优化耦合 从DNP NMR探针中的发射天线到感兴趣的生化样品的微波功率的。 初步结果表明，优化的系统可以将所需的太赫兹功率降低五倍， 足以允许用较低的电源替换回旋管。我们会用电磁学 模拟设计，构建和测试具有更高品质因数的EPR谐振器，以便更有效地耦合 太赫兹能量2.）的情况。为了设计太赫兹功率与样品的最佳耦合，我们必须 知道生物化学样品在低温下的复介电常数（真实的和虚的ε）。我们 将使用矢量网络分析仪测量样品的介电常数。3.）第三章输出的有效传输 从太赫兹源到DNP/NMR样品的功率是先进的微波工程挑战。我们 将进行实验和理论研究，以减少所有传输损耗。4.）我们建议建立和 在527 GHz / 800 MHz（16 T磁场）下测试用于脉冲DNP的强大陀螺放大器，其中高分辨率 目前正在进行DNP实验。陀螺放大器将使用现有的磁铁和电子枪 大大降低了成本。总的来说，这些研究将有助于使DNP/NMR更容易获得和有用。 现代生物化学研究的工具。

The proposed research is focused on fundamental advances in the field of Dynamic Nuclear Polarization (DNP) NMR that will make this powerful technique far more readily available and useful to the national and international biomedical research communities. In DNP NMR, a high frequency microwave source is used to irradiate electron- nuclear transitions, thereby transferring the high spin polarization in the electron spin reservoir to the nuclear spin system through hyperfine and dipolar interactions. The resulting enhancements in NMR signals have been demonstrated to exceed a factor of 400, and thus DNP NMR is now considered a major advance in NMR spectroscopy. The required microwave frequency for the excitation of the electron spin system is in the terahertz regime: 263 GHz, 395 GHz and 527 GHz for 400 MHz, 600 MHz, and 800 MHz 1H frequencies respectively. To date, DNP for magic angle spinning (MAS) NMR experiments has relied on gyrotron oscillators with continuous power output of tens of Watts. Gyrotrons are now commercially available and more than 40 such systems have been installed worldwide in the past decade. However, gyrotrons for DNP are very costly, exceeding the $600k cost limit for NIH Shared Instrument Grants. Gyrotrons are also relatively large, creating additional issues with the demand for lab space and siting. The main thrust of the proposed research is to radically reduce the required power levels for DNP/NMR down to the point where smaller and cheaper sources are available, including terahertz klystrons and solid-state sources. This will be done by dramatically improving the coupling of power to the sample and by significantly improving the transmission efficiency of the transmission lines. We propose these specific research activities: 1.) We will use state-of-the-art electromagnetics simulations to optimize the coupling of the microwave power from the launching antenna in the DNP NMR probe to the biochemical sample of interest. Preliminary results show that an optimized system can reduce the needed terahertz power by a factor of five, sufficient to allow replacement of the gyrotron by a lower power source. We will use our electromagnetics simulations to design, build and test EPR resonators with higher quality factors in order to more efficiently couple the terahertz power. 2.) In order to design optimized coupling of the terahertz power to the sample, we must know the complex permittivity (real and imaginary ε) of the biochemical samples at cryogenic temperatures. We will measure the sample permittivity using a vector network analyzer. 3.) The efficient transmission of the output power from the terahertz source to the DNP/NMR sample is an advanced microwave engineering challenge. We will conduct experimental and theoretical research to reduce all transmission losses. 4.) We propose to build and test a powerful gyroamplifier for pulsed DNP at 527 GHz / 800 MHz (16T magnetic field), where high resolution DNP experiments are currently being performed. The gyroamplifier will use an existing magnet and electron gun to greatly reduce the cost. Collectively, these studies will help make DNP/NMR a far more accessible and useful tool in modern biochemistry research.