Advanced Instrumentation for Dynamic Nuclear Polarization NMR Research

拟议的研究集中在动态核极化(DNP)领域的基本进展。 核磁共振将使这项强大的技术更容易获得，并对国内和国际有用 生物医学研究社区。在DNP核磁共振中，高频微波源被用来照射电子。 核跃迁，从而将电子自旋库中的高自旋极化转移到核 通过超精细和偶极相互作用的自旋系统。由此产生的核磁共振信号增强是 被证明超过了400倍，因此DNP核磁共振现在被认为是核磁共振的一大进步 光谱学。激发电子自旋系统所需的微波频率是太赫兹。 系统：400 MHz、600 MHz和800 MHz 1H频率分别为263 GHz、395 GHz和527 GHz。至 DATE，魔角旋转(MAS)核磁共振实验的DNP依赖于回旋振荡器与连续 输出功率为几十瓦。回旋管现在已经商业化，有40多个这样的系统 在过去的十年里已经在世界各地安装了。然而，用于DNP的回旋管非常昂贵，超过60万美元 美国国立卫生研究院共享仪器补助金的成本限制。回旋管也相对较大，这会带来额外的问题 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/核磁共振的功率水平下降到有更小和更便宜的来源可用，包括 太赫兹速调管和固态源。这将通过极大地改善电力与 并通过样机显著提高了传输线的传输效率。我们提出这些建议 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核磁共振探头中发射天线到感兴趣的生化样品的微波功率。 初步结果表明，优化的系统可以将所需的太赫兹功率降低到原来的1/5， 足以用较低的电源替换回旋管。我们会用我们的电磁学 模拟设计、制造和测试具有更高品质因数的EPR谐振器，以便更有效地耦合 太赫兹的能量。2.)为了设计太赫兹功率与样品的优化耦合，我们必须 知道生化样品在低温下的复介电常数(实数和虚数ε)。我们 将使用矢量网络分析仪测量样品的介电常数。3.)输出的有效传输 从太赫兹源到DNP/核磁共振样品的功率是一个先进的微波工程挑战。我们 将进行实验和理论研究，以降低所有传输损耗。4.)我们建议建造和 在527 GHz/800 MHz(16T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/核磁共振更容易获得和更有用 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.