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

描述(申请人提供)：三十多年来，高分辨率(HR)核磁共振(核磁共振)一直是均相体系中所有类型的大小分子结构和功能阐明的领先分析技术。最近，魔角旋转(MAS)与高场高分辨核磁共振相结合，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谱显示，与非恶性乳腺组织相比，磷胆碱水平显著增加，如果HR-MAS探针的信噪比(SNR)能够充分提高，似乎有可能在许多其他病理组织中识别其他明确的标志物。MAS还被成千上万的核磁共振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核磁共振探头已经可以与低温冷却的样品线圈一起使用，由于其信噪比提高了四倍，这将给核磁共振领域带来革命性的变化。在HR-MAS中，信噪比似乎有更大的改善。到目前为止，我们的工作证明了在室温MAS实验中，通过将样品线圈和调谐元件低温冷却到25K，同时使用噪声系数(Nf)为1.0的标准前置放大器，信噪比提高了三倍。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以及其他改进，预计信噪比将有另一倍的提高。由于电路中使用的电容器的高压击穿特性较差，样品中产生的旋转框架场强(B1)受到严重限制。我们在这里介绍了通过开发可处理超过3.5千伏峰值电压的超高Q陶瓷圆盘电容器，将所有通道上的B1场强从30 kHz提高到70 kHz以上的基础。在低于90K的温度下旋转也将得到实质性的改进，这将使S/N在许多系统中获得进一步的进展，并改善分子动力学的信息。与公众健康相关：核磁共振(核磁共振)一直是确定生物、化学和医学中复杂分子结构的最有效的分析工具之一，但对于不能溶于合适液体的非常大的分子，核磁共振技术的成功有限。本文提出的被称为CryoMAS核磁共振探针的仪器开发如果成功，将使非常昂贵的核磁共振光谱仪所需的时间减少30到100倍(从几个月减少到几天或几个小时)，从而使确定数十万个目前结构未知的生物和化学重要大分子的结构成为现实。这对药物开发、催化剂和酶很重要，仅举几例。

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.