Development of Solid State NMR Methods and Technology

固态核磁共振方法和技术的发展

• 批准号: 8939521
• 负责人: ROBERT TYCKO
• 金额: $ 54.33万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8939521
• 关键词: Address; Area; Biopolymers; Caliber; Cell Nucleus; Cells; Chemicals; Development; Electrons; Equipment; Family; Free Radicals; Frequencies; Goals; Image; Imaging Phantoms; Imaging technology; Magnetic Resonance Imaging; Measurement; Measures; Methods; Noise; Nuclear; Nuclear Magnetic Resonance; Physiologic pulse; Polystyrenes; Proteins; Radio; Resolution; Rotation; Sampling; Sapphire; Signal Transduction; Solubility; Solutions; System; Techniques; Technology; Temperature; Testing; Three-Dimensional Image; Torsion; Water; Work; aqueous; cold temperature; design and construction; improved; irradiation; microwave electromagnetic radiation; radiofrequency; research study; solid state nuclear magnetic resonance; theories

Progress in FY2014 was made in the following areas: (1) MECHANISMS OF DYNAMIC NUCLEAR POLARIZATION IN LOW-TEMPERATURE SOLID STATE NMR. Dynamic nuclear polarization (DNP) is a physical phenomenon in which couplings between electron spins and nuclear spins allows the large spin polarization of electrons to be transferred to nuclei when the electron spins are irradiated by resonant microwaves. The large spin polarization greatly enhances the strength of nuclear magnetic resonance signals, allowing NMR measurements to be carried out on much smaller or more dilute samples. In recent work, we developed a comprehensive theory that explains the principal DNP mechanism in low-temperature solid state NMR experiments. In FY2014, we demonstrated that rapid sample rotation alone, even in the absence of microwave irradiation, leads to a strong perturbation of nuclear spin polarizations. Rapid sample rotation is almost always employed in biomolecular solid state NMR measurements, so these results have important practical consequences. (2) DEVELOPMENT OF TRIRADICAL POLARIZING AGENTS FOR DNP. We have synthesized a family of chemical compounds, each containing three nitroxide free-radical groups, that can be used in DNP measurements. The new compounds have improved solubilities in aqueous solutions near neutral pH, making them compatible with most biomolecular solid state NMR measurements. We find that these triradical compounds produce larger net NMR signal enhancements and more rapid build-up of signals than related compounds that are used by other groups. (3) MRI MICROSCOPY. We have designed and construct a magnetic resonance imaging (MRI) system for studies of single cells and cell clusters. The MRI system contains a radio-frequency microcoil (150 micron diameter) and three-axis field gradient coils, all mounted within a set of stacked sapphire plates within a volume of approximately 1 cubic centimeter. Field gradients on the order of 1 Gauss per micron can be produced with 100 amp current pulses, implying that 3D images with isotropic spatial resolution below 1 micron are feasible, in principle. Test images of "phantom" samples (20-micron polystyrene beads in water) indicate that 3D isotropic resolution of 5 microns can be obtained at room temperature, limited by signal-to-noise considerations. Experiments at low temperatures are planned, where signal-to-noise will be inherently higher and image resolution can consequently also be higher, especially with DNP enhancements of signal strengths.

2014财年在以下几个方面取得了进展： (1) 低温固态核磁共振动态核极化机制。 动态核极化（DNP）是一种物理现象，当电子自旋受到谐振微波照射时，电子自旋与核自旋之间的耦合使得电子的大自旋极化转移到原子核。 大自旋极化极大地增强了核磁共振信号的强度，使得核磁共振测量可以在更小或更稀的样品上进行。 在最近的工作中，我们开发了一种综合理论来解释低温固态 NMR 实验中的主要 DNP 机制。 在 2014 财年，我们证明，即使在没有微波照射的情况下，仅快速样品旋转也会导致核自旋极化的强烈扰动。 生物分子固态 NMR 测量几乎总是采用快速样品旋转，因此这些结果具有重要的实际意义。 (2)DNP三自由基偏光剂的开发。 我们合成了一系列化合物，每种化合物都含有三个硝基氧自由基基团，可用于 DNP 测量。 新化合物提高了在接近中性 pH 值的水溶液中的溶解度，使其与大多数生物分子固态 NMR 测量兼容。 我们发现这些三自由基化合物比其他组使用的相关化合物产生更大的净 NMR 信号增强和更快的信号建立。 (3)核磁共振显微镜。 我们设计并构建了用于研究单细胞和细胞簇的磁共振成像（MRI）系统。 MRI 系统包含射频微线圈（直径 150 微米）和三轴场梯度线圈，全部安装在一组堆叠的蓝宝石板内，体积约为 1 立方厘米。 100 安培的电流脉冲可以产生每微米 1 高斯量级的场梯度，这意味着各向同性空间分辨率低于 1 微米的 3D 图像原则上是可行的。 “模型”样品（水中的 20 微米聚苯乙烯珠）的测试图像表明，受信噪比考虑的限制，在室温下可以获得 5 微米的 3D 各向同性分辨率。 计划在低温下进行实验，其中信噪比本质上会更高，图像分辨率也会因此更高，特别是在 DNP 增强信号强度的情况下。