CryoMAS Probes for Order-of-Magnitude Advance in S/N in NMR of Solids

CryoMAS 探针可实现固体 NMR 中信噪比的数量级提升

• 批准号: 8336814
• 负责人: Francis DAVID Doty
• 金额: $ 56.6万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8336814
• 关键词: A-factor (Streptomyces); Beryllium; Biochemistry; Biology; Businesses; Cancer Diagnostics; Catalysis; Cell Membrane Proteins; Ceramics; Characteristics; Chemistry; Complex; Consumption; Coupled; Development; Device or Instrument Development; Diagnostic tests; Electrons; Elements; Enzymes; Equipment; Fingers; Frequencies; Gases; Goals; Heating; Helium; Hospitals; Hour; Liquid substance; Magic; Magnetism; Malignant - descriptor; Mammary Gland Parenchyma; Marketing; Medicine; Membrane Proteins; Minor; Molecular Structure; Names; Noise; Non-Malignant; Nuclear; Nuclear Magnetic Resonance; Pathology; Performance; Phase; Phosphorylcholine; Public Health; Research; Research Personnel; Resolution; Sales; Sampling; Services; Signal Transduction; Solid; Spectrum Analysis; Structure; System; Techniques; Technology; Temperature; Time; Tissue Sample; Tissues; Transistors; Work; analytical tool; animal tissue; base; catalyst; cost; cryogenics; design; drug development; human tissue; improved; interest; irradiation; macromolecule; magnetic field; malignant breast neoplasm; millimeter; novel; prototype; research study; seal; success; voltage

DESCRIPTION (provided by applicant): Magic Angle Spinning (MAS) is utilized by thousands of Nuclear Magnetic Resonance (NMR) researchers in fields such as macromolecule structure determination, membrane proteins, catalysis, and organo-metallo-complexes. For over three decades, High-Resolution (HR) 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, HR-MAS has been used 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 many other unambiguous markers can be identified for other pathologies if the signal to noise ratio (SNR) of the HR-MAS probe can be increased sufficiently. 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. Even greater improvements in SNR can be achieved with CryoMAS probes of several common types, including 1H/13C/15N and 1H/X. Our work thus far demonstrated about a factor-of-five improvement in SNR in MAS experiments in probes of both of the above types by cryogenically cooling the coils and circuit elements to 25 K while the sample was maintained at room temperature. A substantial additional increase in SNR is expected from a combination of further advances during the Phase II. These advances will include (1) novel coil technology enabling more than a 50% increase in resonator quality factor Q at 25 K in high magnetic fields, (2) refinements in a hermetically sealed spinner design enabling a 25% improvement in magnetic filling factor of the cryocoils, (3) a factor of two increase in the Q of HV ceramic capacitors in the 400-1000 MHz range, and (4) ability to achieve over 75 kHz 1H decoupling field strength in a triple-resonance CryoMAS probe to at least 11.7 T. Substantial improvements in spinning at sample temperatures down to 30 K will also be developed, and provisions for millimeter-wave irradiation will be added to enable Dynamic Nuclear Polarization (DNP) to be easily added. Reducing the sample temperature from 90 K to 40 K in MAS DNP is expected to often in- crease S/N in DNP experiments by an order of magnitude. Additional improvements in S/N will come from further progress in reduction of noise figure (NF) of cryogenically cooled preamps based on the Enhancement mode Pseudomorphic High Electron Mobility Transistors (E-PHEMT). Key Words: solids NMR probes, cryoprobes, HR-MAS, cancer diagnostic tests, molecular structures, cryogenic preamps, dynamic nuclear polarization (DNP)

描述（由申请人提供）：魔角旋转（MAS）被数千名核磁共振（NMR）研究人员用于高分子结构测定、膜蛋白、催化和有机金属络合物等领域。三十多年来，高分辨率（HR）NMR一直是均相体系中所有类型分子（无论大小）结构和功能解析的领先分析技术。最近，HR-MAS已被用于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，则似乎可以鉴定出许多其他明确的标记物用于其他病理。 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。使用几种常见类型的CryoMAS探针，包括1H/13 C/15 N和1H/X，可以实现SNR的更大改善。到目前为止，我们的工作表明，在MAS实验中，通过将线圈和电路元件低温冷却至25 K，同时将样品保持在室温下，上述两种类型的探针的SNR提高了约五分之一。预计第二阶段期间的进一步进展将使信噪比大幅增加。这些进展将包括：（1）新型线圈技术，在25 K高磁场条件下，谐振器品质因数Q值提高50%以上;（2）密封旋转器设计的改进，使低温线圈的磁填充因数提高25%;（3）在400-1000 MHz范围内，HV陶瓷电容器的Q值提高两倍;以及（4）在三重共振CryoMAS探针中实现超过75 kHz的1H去偶场强度至至少11.7T的能力。还将开发在样品温度降至30 K的情况下旋转的实质性改进，并将增加毫米波辐照的规定，以使动态核极化（DNP）能够轻松添加。在MAS DNP中将样品温度从90 K降低到40 K，预计通常会使DNP实验中的S/N增加一个数量级。信噪比的进一步提高将来自于基于增强型赝晶高电子迁移率晶体管（E-PHEMT）的低温冷却晶体管的噪声系数（NF）的进一步降低。关键词：固体核磁共振探针，冷冻探针，HR-MAS，癌症诊断测试，分子结构，低温探针，动态核极化（DNP）