Closed-Loop MAS-DNP-NMR at 30 K for Affordable Dramatic Gains in S/N

30 K 下的闭环 MAS-DNP-NMR 可实现信噪比的大幅提升

• 批准号: 9336946
• 负责人: Francis DAVID Doty
• 金额: $ 70.02万
• 依托单位: DOTY SCIENTIFIC, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9336946
• 关键词: Biological; Budgets; Complex; Consumption; Databases; Deposition; Development; Helium; Hour; Laboratories; Liquid substance; Magic; Membrane Proteins; Methods; Minor; Molecular Structure; Noise; Nuclear; Nuclear Magnetic Resonance; Phase; Platelet Factor 4; Price; Proteins; Publishing; Recycling; Research Personnel; Running; Sampling; Side; Small Business Innovation Research Grant; Solid; Source; Structure; System; Techniques; Technology; Temperature; Testing; Time; Vent; Vertebral column; catalyst; cold temperature; cost; cost effective; cryogenics; design; experimental study; improved; instrumentation; irradiation; macromolecule; magnetic field; microwave electromagnetic radiation; millimeter; operation; protein structure; public health relevance; solid state; solid state nuclear magnetic resonance; stem; tool

 DESCRIPTION (provided by applicant): NMR is arguably the most powerful analytical technique for structure determination and function elucidation in molecules of all types, but there are complex challenges for biological macromolecules. Dynamic Nuclear Polarization (DNP) with Magic Angle Spinning (MAS) has recently demonstrated S/N gains of up to two orders of magnitude at ~100 K (the lower-temperature bound using N2-MAS technology) compared to conventional NMR-MAS in many solids. Despite this enormous benefit, the adaptation rate of DNP will be severely limited by its very high price tag ($2-4M), mostly because DNP experiments at field strengths greater 3.5 T and operating in the 90-110 K range require an expensive gyrotron for the high-power millimeter-wave (mmw) irradiation, and that in turn requires a special magnet with superconducting sweep coils. Preliminary experiments at ~30 K (that consumed liquid helium at the rate of up to 250 L/day) have shown the potential for the use of low-power solid-state mmw sources and order-of-magnitude higher S/N for DNP - if suitable MAS-DNP probes could be developed. However, 30K-MAS-DNP will necessitate helium recycling, improved sample spinner designs, and a number of additional technical advances. This SBIR project will enable 30K-MAS-DNP by developing: (A) the needed high-stability 30-K helium-spinner technology, (B) the needed high-efficiency closed-loop cryogenic helium recycling system, (C) complete quad-resonance and quint-resonance multi-nuclear (1H-19F/X/Y/e- and 1H-19F /X/Y/Z/e-) DNP probes with auto sample exchange and variable temperature (VT) operation from 30 K to 400 K. The probes will be demonstrated at 7 T, 11.7 T, 14 T, and 16.4 T using a combination of facilities at DSI, the National High Magnetic Field Laboratory, and customers. Compared to current state-of-the-art (100 K) MAS-DNP instrumentation, the proposed fully optimized MAS-DNP probes at 30 K will often improve sample throughput by one to two orders of magnitude. The information needed for determining detailed molecular structures could then be obtained on many complex biomolecules, catalysts, and other solids in a few hours rather than days or weeks. As demonstrated during the Phase I: the combination of increased Boltzmann factor, dramatically reduced rf circuit noise temperature, and substantially increased circuit Q, combine to yield most of these throughput gains. Additional significant gains will come from incorporation of a gradient coil for coherence selection. Reduction in system cost will stem from the dramatic increase in T1e below 50 K, enabling the use of low- cost solid-state millimeter-wave sources and standard wide-bore magnets. The helium purification and recycling system this project will develop to enable 30K-DNP will also make it straightforward and cost-effective for the facility to implement recycling fo all the helium it requires for its cryo-magnets. The additional hardware required for helium liquefaction will be relatively minor. Hence, not only will this project advance throughput of solis NMR by more than an order of magnitude, it will also enable cost-effective recycling of helium at the larger NMR facilities.

 描述（由申请人提供）：NMR可以说是用于所有类型的分子中的结构测定和功能阐明的最强大的分析技术，但是存在以下缺点： 是生物大分子面临的复杂挑战。动态核极化（DNP）与魔角旋转（MAS）最近已经证明了S/N增益高达两个数量级在~100 K（使用N2-MAS技术的较低温度范围）相比，在许多固体中的常规NMR-MAS。尽管有这个巨大的好处，DNP的适应率将受到其非常高的价格标签（2 - 4 M美元）的严重限制，主要是因为在场强大于3.5 T和在90-110 K范围内工作的DNP实验需要一个昂贵的回旋管用于高功率毫米波（mmw）辐射，这反过来又需要一个特殊的磁体与超导扫描线圈。 在~30 K（消耗液氦的速率高达250 L/天）的初步实验表明，如果可以开发出合适的MAS-DNP探针，则有可能使用低功率固态毫米波源和更高数量级的S/N。然而，30 K-MAS-DNP将需要氦回收、改进的样品旋转器设计和一些额外的技术进步。 该SBIR项目将通过开发以下内容实现30 K-MAS-DNP：（A）所需的高稳定性30 K氦旋转器技术，（B）所需的高效闭环低温氦再循环系统，（C）完全四共振和五共振多核（1H-19 F/X/Y/e-和1H-19 F/X/Y/Z/e-）DNP探针，带自动样品交换和30 K至400 K的变温（VT）操作。探头将在7 T、11.7 T、14 T和16.4 T下使用DSI、国家高磁场实验室和客户的设施组合进行演示。 与目前最先进的（100 K）MAS-DNP仪器相比，所提出的完全优化的MAS-DNP探针在30 K下通常会将样品通量提高一到两个数量级。确定分子结构所需的信息可以在几个小时而不是几天或几周内获得许多复杂的生物分子，催化剂和其他固体。如第一阶段所示：玻尔兹曼因子增加、射频电路噪声温度显著降低、电路Q值显著增加，这些因素的组合联合收割机产生了大部分吞吐量增益。额外的显著增益将来自于用于相干性选择的梯度线圈的结合。系统成本的降低将源于T1 e在50 K以下的急剧增加，从而能够使用低成本固态毫米波源和标准宽孔磁体。 该项目将开发的氦净化和回收系统将使30 K-DNP成为可能，这也将使该设施能够直接和具有成本效益地回收其低温磁体所需的所有氦。氦液化所需的额外硬件将相对较小。因此，该项目不仅将solis NMR的吞吐量提高一个数量级以上，还将使大型NMR设施的氦气回收具有成本效益。