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）：魔术角旋转（MAS）在诸如大分子结构测定，膜蛋白，催化和Orano-Metallo-complexes等领域中使用了数千个核磁共振（NMR）研究人员。在过去的三十年中，高分辨率（HR）NMR一直是一种领先的分析技术，用于在同质系统中的所有类型的大小分子的结构和功能阐明。最近，HR-MAS已被用来将技术扩展到不均匀的系统，例如人体和动物组织。与非恶性乳腺组织相比，恶性乳腺癌组织的1H HR-MAS光谱显示，如果HR-MAS探测的HR-MAS探测器的信号比（SNR）可以增加足够的增加，则可以鉴定出许多其他明确的标记物的磷胆碱水平急剧增加。 液体的HR NMR探针已通过低温冷却的样品线圈获得，由于其在SNR中提高了四分之二，它们正在彻底改变NMR领域。通过几种常见类型（包括1H/13C/15N和1H/X）的冷冻探针可以实现SNR的更大改善。迄今为止，我们的工作证明了在MAS实验中，在两种类型的MAS实验中，SNR的五倍改进，通过将线圈和电路元件冷却至25 K，而样品保持在室温下。在II期期间进一步进步的组合预计SNR会增加SNR。这些进步将包括（1）新型的线圈技术，在高磁场中25 K处的谐振质量因子Q增加了50％以上，（2）在密封的密封的旋转器设计中进行的改进，可在高度密封的旋转器设计中提高25％的磁性填充因子的25％，（3）在HV Ceramic Cagitors in 4的Q范围内增加了2次，而45 kramik kermik ins in of HV Ceramic Cavandors in 45）and（3）4.45）and（4）4.45）and（4）4.45）and（4）kymhz ins in 45）。还将开发出三谐和冷冻瘤探针中至少11.7 T的脱钩场强度。还将开发出降至30 K的样品温度下旋转的实质改善，并且将添加用于启用动态核极化（DNP）的毫米波照射的规定，以便于添加。在MAS DNP中，将样品温度从90 K降低到40 K，预计在DNP实验中经常通过数量级将S/N降低。基于增强模式假形态高电子迁移式晶体管（E-Phemt），S/N的其他改进将来自降低低温冷却前置放大器的噪声图（NF）的进一步进步。关键词：固体NMR探针，冷冻探针，HR-MA，癌症诊断测试，分子结构，低温前置放大器，动态核极化（DNP）