A Cryo-coil MAS 1H/13C/2H/15N Probe for Highest S/N in NMR of Solids

描述（由申请人提供）：三十多年来，高分辨率（HR）核磁共振（NMR）一直是均相系统中所有类型（大小）分子结构和功能解析的领先分析技术。最近，魔角旋转（MAS）已与高场HR-NMR相结合，将该技术扩展到非均匀系统，如人类和动物组织。恶性乳腺癌组织的1H HR-MAS光谱显示与非恶性乳腺组织相比磷酸胆碱水平显著增加，并且如果HR-MAS探针的信噪比（SNR）可以充分增加，则似乎可以为许多其他病理鉴定其他明确的标记物。MAS也被成千上万的NMR研究人员用于大分子结构测定、有机金属络合物和膜蛋白等领域。用于液体的HR NMR探头已经可以与低温冷却样品线圈一起使用，由于其SNR的四分之一改善，这些线圈正在彻底改变NMR领域。在HR-MAS中，SNR可能会有更大的改善。到目前为止，我们的工作表明，在室温MAS实验中，通过低温冷却样品线圈和调谐元件到25 K，同时使用噪声系数（NF）为1.0的标准前置放大器，SNR提高了三分之一。通过开发噪声系数低于0.3的低温冷却低噪声前置放大器和其他改进，预期SNR的另一个2倍增加。在样品中产生的磁场强度（B1）受到电路中使用的电容器的不良高压击穿特性的严重限制。我们在此介绍了通过开发超高Q陶瓷圆盘电容器将所有通道的B1场强从30 kHz提高到70 kHz以上的基础，该电容器可处理超过3.5 kV的峰值电压。还将开发在低于90 K的温度下纺丝的实质性改进，这在许多系统中提供了S/N的进一步增益和分子动力学的改进信息。公共卫生相关性：核磁共振（NMR）是生物学、化学和医学中确定复杂分子结构的最有效的分析工具之一，但对于不溶于适当液体的非常大的分子，NMR技术的成功有限。本文提出的称为CryoMAS NMR探针的仪器开发如果成功，将使非常昂贵的NMR光谱仪所需的时间减少30至100倍（从数月到数天或数小时），从而使其能够实际确定数十万生物和化学重要的大分子的结构，这些大分子的结构目前尚不清楚。这对药物开发、催化剂和酶等都很重要。

DESCRIPTION (provided by applicant): For over three decades, High-Resolution (HR) Nuclear Magnetic Resonance (NMR) has been a leading analytical technique for structure and function elucidation of molecules of all types, large and small, in homogeneous systems. More recently, Magic Angle Spinning (MAS) has been combined with high-field HR-NMR to extend the technique to inhomogeneous systems, such as human and animal tissues. The 1H HR-MAS spectrum of malignant breast cancer tissue shows dramatically increased levels of phosphocholine compared to nonmalignant breast tissue, and it appears likely that other unambiguous markers can be identified for many other pathologies if the signal to noise ratio (SNR) of the HR-MAS probe can be increased sufficiently. MAS is also utilized by thousands of NMR researchers in fields such as macromolecule structure determination, organo-metallo-complexes, and membrane proteins. HR NMR probes for liquids have become available with cryogenically cooled sample coils that are revolutionizing the field of NMR owing to their factor-of-four improvement in SNR. Greater improvements in SNR appear likely in HR-MAS. Our work thus far demonstrated a factor-of-three improvement in SNR in room temperature MAS experiments by cryogenically cooling the sample coil and tuning elements to 25 K while using a standard preamp with noise figure (NF) of 1.0. Another factor-of-two increase in SNR is expected by developing a cryogenically cooled low noise preamp with noise figure below 0.3 and other improvements. The rotating-frame field strength (B1) produced in the sample was severely limited by the poor high-voltage breakdown characteristics of capacitors used in the circuit. We present here, the basis for increasing the B1 field strength from 30 kHz to over 70 kHz on all channels by developing ultra-high Q ceramic disc capacitors that will handle peak voltages in excess of 3.5 kV. Substantial improvements in spinning at temperatures below 90 K will also be developed, which gives further gains in S/N in many systems and improved information on molecular dynamics. PUBLIC HEALTH RELEVANCE: Nuclear magnetic resonance (NMR) has been one of the most effective analytical tools for determining the structure of complex molecules in biology, chemistry, and medicine, but the NMR technique has had limited success for the very large molecules that are not soluble in suitable liquids. The instrument development proposed herein, called a CryoMAS NMR probe, if successful, will reduce the amount of time needed on very expensive NMR spectrometers by a factor of 30 to 100 (from months to days or hours) and thus make it practical to determine the structures of hundreds of thousands of biologically and chemically important macro-molecules for which structures are currently unknown. This is important to drug developments, catalysts, and enzymes, to name but a few.