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

 描述(申请人提供)：核磁共振可以说是所有类型的分子中结构确定和功能阐明的最强大的分析技术，但 是生物大分子面临的复杂挑战。魔角自旋动态核极化技术最近在许多固体中展示了在~100K(使用N_2-MAS技术的较低温度范围)下的S/N增益高达两个数量级。尽管有这种巨大的好处，但DNP的适配率将受到其非常高的价格标签(200-400万美元)的严重限制，主要是因为DNP在场强大于3.5T、工作在90-110K范围内的实验需要昂贵的回旋管来进行高功率毫米波(MMW)照射，而这反过来又需要带有超导扫描线圈的特殊磁体。在~30K(以高达250K的L/天的速度消耗液氦)的初步实验表明，如果能够开发出合适的MAS-DNP探针，则有可能使用低功率固态毫米波源和数量级高出数量级的S/N。然而，30K-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。这个SBIR项目将通过开发：(A)所需的高稳定性30K氦旋转技术，(B)所需的高效闭路低温氦循环系统，(C)完全四共振和五共振多核(1H-19F/X/Y/e-和1H-19F/X/Y/Z/e-)DNP探测器，具有自动样品交换和变温(VT)操作，从30K到400K，从而实现30K-MAS-DNP。和16.4T，使用DSI、国家强磁场实验室和客户的设施组合。与目前最先进的(100K)MAS-DNP仪器相比，提出的30K下完全优化的MAS-DNP探头通常会将样品吞吐量提高一到两个数量级。然后，确定详细分子结构所需的信息可以在几个小时内获得许多复杂的生物分子、催化剂和其他固体的信息，而不是几天或几周。正如在第一阶段中所展示的：增加的Boltzmann因数、显著降低的RF电路噪声温度和显著增加的电路Q相结合，产生了这些吞吐量增益中的大部分。其他显著的收益将来自结合用于相干选择的梯度线圈。系统成本的降低将源于T1e在50K以下的急剧增加，从而能够使用低成本的固态毫米波源和标准的大口径磁铁。该项目将开发的氦提纯和回收系统能够实现30K-DNP，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少。因此，该项目不仅将Solis核磁共振的产量提高一个数量级以上，还将使更大的核磁共振设施能够经济高效地回收氦。

 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.