A Millimeter-wave Tunable Cavity for Ultra-sensitive Solids and Liquids DNP-NMR at Low Budget

用于低预算超灵敏固体和液体 DNP-NMR 的毫米波可调谐腔

• 批准号: 8834031
• 负责人: Francis DAVID Doty
• 金额: $ 19.73万
• 依托单位: DOTY SCIENTIFIC, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8834031
• 关键词: Aluminum Oxide; Biological; Biomedical Research; Budgets; Cellular Membrane; Characteristics; Chemicals; Complex; Data; Databases; Deposition; Development; EKG P Wave; Electrons; Heating; Imaging Techniques; Laboratories; Lipids; Liquid substance; Magic; Magnetic Resonance Imaging; Magnetism; Membrane Proteins; Methods; North Carolina; Nuclear; Nuclear Magnetic Resonance; Optics; Phase; Physiologic pulse; Price; Production; Proteins; Publishing; Pump; Relative (related person); Research Personnel; Resolution; Sample Size; Sampling; Signal Transduction; Simulate; Small Business Technology Transfer Research; Solid; Source; Structure; System; Techniques; Temperature; Testing; Time; Tube; Universities; base; cost; design; design and construction; improved; liquid dynamics; macromolecule; microwave electromagnetic radiation; millimeter; nanostructured; novel; protein structure; public health relevance; research study; simulation; solid state nuclear magnetic resonance; structural biology; technology development; tool; transmission process

 DESCRIPTION (provided by applicant): NMR is probably the most powerful and widely used analytical technique for structure determination and function elucidation of molecules of all types, but it suffers from low sensitivity, particularly for insoluble biological macromolecules. Dynamic Nuclear Polarization (DNP) with Magic Angle Spinning (MAS) has recently demonstrated S/N gains exceeding two orders of magnitude at ~100 K compared to conventional MAS-NMR in many biological solids. Despite this enormous benefit to biomedical research, the adaptation rate of DNP will be severely limited by its very high price tag (currently $1.8-4M), mostly because of the special magnet (with sweep coils) and expensive gyrotron required, owing to the very poor microwave efficiency of current DNP probes. Our detailed simulations of a novel millimeter wave (mmw) DNP cavity have shown the potential for achieving the needed electron spin saturation with two orders of magnitude lower microwave power than the existing MAS-DNP designs for samples of similar volume (1-25 L) at the same B0 and temperature. The proposed novel DNP cavity is initially compatible only with static (non-spinning) methods, and the linewidths from static solids NMR techniques are always much greater than in MAS. However, static high-power methods, such as PISEMA, have been as fruitful as MAS methods in yielding structures of large, complex, helical membrane proteins because of the unique capability to provide correlated dipolar and anisotropic chemical shift data needed to resolve sign degeneracies. A novel stacked-plate cavity arrangement of nanostructured substrate containing macroscopically aligned and hydrated membrane proteins developed by collaborating NCSU team dramatically reduces sample heating enabling substantial DNP S/N enhancements even for lossy liquid samples at or near RT with substantially improved spectral resolution. Related cavity designs compatible with MAS-DNP, inspired by the static-DNP cavity, will also be simulated. The static DNP cavity and probe that will be initially developed for 7 T is expected to yield two orders of magnitude gain in S/N for a wide range of solids NMR experiments, and it will do so with two orders of magnitude lower mmw power than competing MAS-DNP designs. This will make it possible for virtually all current NMR groups to bring static H/X/Y/e- DNP capabilities into their labs - for both solids and liquids - for a total entry budget of under $150K, including the 0.05-0.3 W mmw source, DNP probe, waveguides, and transitions - all scalable to very high fields. Development of the Doty static-DNP cavity could allow the number of groups doing DNP-NMR worldwide to increase from a handful to hundreds over the next four to eight years. Overall, the proposed technology development is expected to provide biomedical researchers with tremendous new opportunities for the structure-function studies of membrane proteins and cellular membrane systems.

 描述（由申请人提供）：NMR 可能是用于所有类型分子的结构测定和功能阐明的最强大和最广泛使用的分析技术，但它的灵敏度较低，特别是对于具有动态核极化（DNP）的不溶性生物大分子。最近，在许多生物固体中，魔角旋转 (MAS) 的信噪比比传统的 MAS-NMR 提高了两个数量级，尽管这对生物医学有巨大的好处。研究表明，DNP 的适应率将因其非常高的价格而受到严重限制（目前 1.8-4M 美元），主要是因为当前 DNP 探头的微波效率非常差，需要特殊磁铁（带有扫描线圈）和昂贵的回旋管，我们对新型毫米波 (mmw) DNP 腔的详细模拟显示了其潜力。在相同的 B0 和温度下，对于相似体积（1-25 µL）的样品，以比现有 MAS-DNP 设计低两个数量级的微波功率实现所需的电子自旋饱和。 DNP 腔最初仅与静态（非旋转）方法兼容，并且静态固体 NMR 技术的线宽始终比 MAS 中的线宽大得多。但是，PISEMA 等静态高功率方法与 MAS 方法一样富有成效。由于具有提供解决符号简并所需的相关偶极和各向异性化学位移数据的独特能力，因此可以产生大型、复杂、螺旋膜蛋白的结构。 NCSU 团队合作开发的宏观排列和水合膜蛋白可显着降低样品加热，即使对于处于或接近室温的有损液体样品，也能显着提高 DNP 信噪比，并且受静态影响，与 MAS-DNP 兼容的相关腔体设计也得到了显着提高。 -DNP 腔，最初为 7 T 开发的静态 DNP 腔和探头预计将为各种固体 NMR 实验产生两个数量级的信噪比增益。与竞争的 MAS-DNP 设计相比，毫米波功率低两个数量级，这将使所有当前 NMR 团队能够将静态 H/X/Y/e-DNP 功能引入其实验室 - 对于几乎固体和液体。 - 总入门预算低于 15 万美元，包括 0.05-0.3 W 毫米波源、DNP 探头、波导和转换 - 所有这些都可扩展到非常高的领域 Doty 静态 DNP 的开发。空腔可以使世界范围内进行 DNP-NMR 的研究小组数量在未来四到八年内从少数增加到数百个。总体而言，拟议的技术开发预计将为生物医学研究人员的结构功能研究提供巨大的新机会。膜蛋白和细胞膜系统。