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

用于固体 NMR 中最高信噪比的低温线圈 MAS 1H/13C/2H/15N 探头

• 批准号: 7670986
• 负责人: Francis DAVID Doty
• 金额: $ 21.85万
• 依托单位: DOTY SCIENTIFIC, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-15 至 2010-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7670986
• 关键词: Achievement; Age; Biology; Breast Cancer Detection; Ceramics; Characteristics; Chemicals; Chemistry; Clinical; Complex; Custom; Device or Instrument Development; Diagnostic; Elements; Enzymes; Equipment; Frequencies; Gases; Generations; Goals; Helium; Hour; Human; Liquid substance; Magic; Magnetism; Malignant - descriptor; Mammary Gland Parenchyma; Medicine; Membrane Proteins; Methods; NMR Spectroscopy; Names; Nitrogen; Noise; Non-Malignant; Nuclear; Nuclear Magnetic Resonance; Pathology; Performance; Phase; Phosphorylcholine; Polymers; Predisposition; Radio; Research Personnel; Resolution; Sampling; Signal Transduction; Small Business Innovation Research Grant; Solid; Structure; System; Techniques; Technology; Temperature; Testing; Time; Tissue Sample; Tissues; Vacuum; Work; analytical tool; animal tissue; base; catalyst; cost; cryogenics; design; drug development; improved; layered ceramics; macromolecule; malignant breast neoplasm; molecular dynamics; public health relevance; research study; simulation; success; voltage

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.

描述（由申请人提供）：三十多年来，高分辨率（HR）核磁共振（NMR）一直是用于阐明均质系统中所有类型（无论大小）分子的结构和功能的领先分析技术。最近，魔角旋转 (MAS) 与高场 HR-NMR 相结合，将该技术扩展到非均匀系统，例如人类和动物组织。与非恶性乳腺组织相比，恶性乳腺癌组织的 1H HR-MAS 谱显示磷酸胆碱水平显着增加，并且如果 HR-MAS 探针的信噪比 (SNR) 能够充分增加，则似乎可以为许多其他病理学鉴定其他明确的标记物。 MAS 还被大分子结构测定、有机金属复合物和膜蛋白等领域的数千名 NMR 研究人员使用。用于液体的 HR NMR 探头已配备低温冷却样品线圈，由于其 SNR 提高了四倍，正在彻底改变 NMR 领域。 HR-MAS 中的 SNR 可能会出现更大的改善。迄今为止，我们的工作证明，通过将样本线圈和调谐元件低温冷却至 25 K，同时使用噪声系数 (NF) 为 1.0 的标准前置放大器，室温 MAS 实验中的 SNR 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，预计信噪比将再提高两倍。样品中产生的旋转框架场强（B1）受到电路中使用的电容器较差的高压击穿特性的严重限制。我们在此介绍通过开发可处理超过 3.5 kV 峰值电压的超高 Q 陶瓷盘电容器，将所有通道上的 B1 场强从 30 kHz 提高到 70 kHz 以上的基础。还将对低于 90 K 温度下的纺丝进行重大改进，从而进一步提高许多系统的信噪比并改进分子动力学信息。公共健康相关性：核磁共振 (NMR) 一直是确定生物学、化学和医学中复杂分子结构的最有效的分析工具之一，但 NMR 技术对于不溶于合适液体的非常大的分子的成功有限。本文提出的仪器开发称为 CryoMAS NMR 探针，如果成功，将把非常昂贵的 NMR 波谱仪所需的时间减少 30 到 100 倍（从几个月到几天或几小时），从而使确定数十万个目前未知的生物和化学重要大分子的结构变得可行。这对于药物开发、催化剂和酶等非常重要。