Manufacture and Supply of Hyperpolarized Chloroform for Use as an NMR Solvent

NMR溶剂用超极化氯仿的制造和供应

• 批准号: 7745858
• 负责人: Neal F Kalechofsky
• 金额: $ 17.33万
• 依托单位: MILLIKELVIN TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7745858
• 关键词: Area; Behavior; Capital; Cell Nucleus; Chloroform; Devices; Environment; Equilibrium; Equipment; Free Radicals; Freezing; Goals; Hour; Liquid substance; Magnetism; Manufactured Supplies; Marketing; Molecular Structure; Noise; Nuclear; Nuclear Magnetic Resonance; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Population; Powder dose form; Predisposition; Proteins; Relaxation; Research Personnel; Sales; Sampling; Sampling Studies; Signal Transduction; Site; Solutions; Solvents; Speed; Surface; Techniques; Technology; Temperature; Time; Work; catalyst; cold temperature; improved; in vivo; magnetic field; physical conditioning; public health relevance; quantum; research study; solute; Area; Behavior; Capital; Cell Nucleus; Chloroform; Devices; Environment; Equilibrium; Equipment; Free Radicals; Freezing; Goals; Hour; Liquid substance; Magnetism; Manufactured Supplies; Marketing; Molecular Structure; Noise; Nuclear; Nuclear Magnetic Resonance; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Population; Powder dose form; Predisposition; Proteins; Relaxation; Research Personnel; Sales; Sampling; Sampling Studies; Signal Transduction; Site; Solutions; Solvents; Speed; Surface; Techniques; Technology; Temperature; Time; Work; catalyst; cold temperature; improved; in vivo; magnetic field; physical conditioning; public health relevance; quantum; research study; solute

DESCRIPTION (provided by applicant): A critical problem that has hampered the range of applications for nuclear magnetic resonance (NMR) is its intrinsically low signal to noise ratio (SNR). This has limited NMR to studies of samples with relatively high concentrations (mM range). A wide array of products has been developed to improve the obtainable SNR in an NMR experiment. Examples include cryoprobes, susceptibility plugs, microcoils, and magnets with ever larger fields. Hyperpolarizing nuclei can produce SNR enhancement factors of 10,000 or more. This tremendous boost in signal makes it possible to study samples with concentration levels in the 5M range. It also greatly reduces the time required to obtain a spectra, eliminating the need for signal averaging. Samples containing nuclei with non zero spin placed in "brute force" conditions (BF)-i.e., very high magnetic fields (typically B > 10 Tesla) and very low temperatures (typically T < 100 mK)--will achieve very high nuclear polarizations. Heretofore, a drawback to using this technique to manufacture hyperpolarized materials has been that the time required for the nuclei to relax to magnetic equilibrium in BF conditions is very long. We will employ a "quantum relaxation switch" (QRS) technique that allows nuclei to quickly relax in a low temperature environment and then be warmed to room temperature without losing undue amounts of polarization. An attractive feature of this technique is that it does not require the addition of free radicals or catalysts to the sample in order to hyperpolarize it. It is a scalable approach that works on all non zero spin nuclei--in particular, chloroform and other liquids commonly used as solvents in NMR experiments and/or to mimic certain in vivo conditions so as to better study the behavior of a variety of proteins and peptides. Hyperpolarized solvents will add value to NMR experiments by transferring polarization to the solute that is being analyzed. This will eliminate the need for bulky and expensive capital equipment to hyperpolarize samples. In addition, because the hyperpolarized solvent is warmed prior to use, samples need not be exposed to arcane physical conditions to be hyperpolarized. Our long term goal is to manufacture and supply HP solvents to the NMR marketplace. Our short term goal is to demonstrate that HP chloroform can be used to enhance the NMR signal from a solute. To achieve these goals, we will carry out the following specific aims: I. Produce high surface area frozen chloroform powders. II. Demonstrate that QRS may be used to produce polarizations of at least 1% in frozen powderized chloroform. III. Demonstrate that hyperpolarization may be maintained in frozen chloroform for hours or longer. IV demonstrates that HP chloroform may be used to enhance NMR signals from a solute at room temperature. PUBLIC HEALTH RELEVANCE: NMR is used to analyze the molecular structure of pharmaceuticals and proteins; however, its' speed and sensitivity has been limited by its intrinsically low signal to noise. Hyperpolarizing a sample can boost the obtainable signal in an NMR experiment by as much as a factor of 10,000. MKT has developed techniques for hyperpolarizing a wide range of materials (in particular, materials such as chloroform that are commonly used as solvents in NMR experiments) and transporting them from site to site so that they may be provided to the NMR researcher as a consumable; this will increase the sensitivity of NMR and allow drugs to be brought to market more quickly and more safely.

描述（由申请人提供）：阻碍核磁共振范围（NMR）范围的一个关键问题是其本质上低信号与噪声比（SNR）。 NMR限制在浓度相对较高（MM范围）的样品的研究中。在NMR实验中，已经开发了各种各样的产品来改善可获得的SNR。示例包括冷冻探针，易感性塞，微型机油和具有较大磁场的磁铁。超极化核可以产生10,000或更多的SNR增强因子。这种信号的巨大提升使得研究浓度水平在5m范围内的样品成为可能。它还大大减少了获得光谱所需的时间，从而消除了对平均信号的需求。含有非零自旋的核的样品将放置在“蛮力”条件下（BF）-I.E。，非常高的磁场（通常为B> 10 Tesla）和非常低的温度（通常为T <100 mk） - 将实现很高的核极性。迄今为止，使用该技术来制造超极化材料的缺点是，在BF条件下核放松身心至磁平衡所需的时间很长。我们将采用“量子松弛开关”（QRS）技术，该技术使核可以在低温环境中快速放松，然后将其温暖到室温，而不会失去不高度的极化。该技术的一个有吸引力的特征是，它不需要在样品中添加自由基或催化剂即可使其超极化。这是一种可扩展的方法，可用于所有非零自旋核（尤其是氯仿和其他用作NMR实验中溶剂和/或模仿某些体内条件的溶剂），以便更好地研究各种蛋白质和肽的行为。超极化溶剂将通过将极化转移到正在分析的溶质中为NMR实验增加值。这将消除对笨重且昂贵的资本设备超极化样品的需求。另外，由于使用前溶剂在使用前会加热，因此样品不必暴露于奥术物理条件中才能被过极化。我们的长期目标是为NMR市场生产和提供HP溶剂。我们的短期目标是证明HP氯仿可用于增强溶质中的NMR信号。为了实现这些目标，我们将执行以下特定目标：I。产生较高的表面积冷冻氯仿粉末。 ii。证明QRS可用于在冷冻粉末化氯仿中产生至少1％的极化。 iii。证明超极化可以在冷冻氯仿中维持数小时或更长时间。 IV证明HP氯仿可用于在室温下从溶质中增强NMR信号。 公共卫生相关性：NMR用于分析药物和蛋白质的分子结构；但是，其速度和灵敏度受到其本质上低信号对噪声的限制。超极化样品可以在NMR实验中提高可获得的信号高达10,000倍。 MKT开发了用于超极化的多种材料（尤其是诸如NMR实验中通常用作溶剂的材料），并将它们从站点运输到现场，以便将其作为可消耗提供给NMR研究人员；这将提高NMR的敏感性，并使药物更快，更安全地推向市场。