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

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（NMR）应用范围的关键问题是其固有的低信噪比（SNR）。这限制了NMR对相对高浓度（mM范围）样品的研究。已经开发了各种各样的产品来提高NMR实验中可获得的SNR。例子包括冷冻探针、磁化率塞、微线圈和具有更大磁场的磁体。超极化核可以产生10，000或更大的SNR增强因子。这种信号的巨大增强使得研究浓度水平在5 M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，消除了对信号平均的需要。包含具有非零自旋的原子核的样品被置于“蛮力”条件（BF）中，即，非常高的磁场（典型地B > 10特斯拉）和非常低的温度（典型地T < 100 mK）将实现非常高的核极化。因此，使用这种技术制造超极化材料的缺点是，在BF条件下，原子核弛豫到磁平衡所需的时间非常长。我们将采用“量子弛豫开关”（QRS）技术，使原子核在低温环境中快速弛豫，然后升温到室温，而不会失去过多的极化。这种技术的一个吸引人的特点是，它不需要添加自由基或催化剂的样品，以hypermarketing. It是一个可扩展的方法，工作在所有非零自旋核-特别是氯仿和其他液体通常用作溶剂在NMR实验和/或模拟某些在体内的条件，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被分析的溶质来增加NMR实验的价值。这将消除对庞大和昂贵的资本设备的需要，以超浓缩样品。此外，由于超极化溶剂在使用前被加热，因此样品不需要暴露于《双城之战》神秘的物理条件下进行超极化。我们的长期目标是为NMR市场生产和供应HP溶剂。我们的短期目标是证明HP氯仿可用于增强溶质的NMR信号。为实现这些目标，我们将实现以下具体目标：一.生产高表面积冷冻氯仿粉末。二.证明QRS波群可用于在冷冻粉末氯仿中产生至少1%的极化。三.证明超极化可以在冷冻氯仿中维持数小时或更长时间。IV表明HP氯仿可用于增强室温下溶质的核磁共振信号。 公共卫生关系：NMR用于分析药物和蛋白质的分子结构;然而，其速度和灵敏度受到其固有的低信噪比的限制。超极化样品可以将NMR实验中可获得的信号提高多达10，000倍。MKT已经开发了用于超极化各种材料（特别是在NMR实验中通常用作溶剂的氯仿等材料）并将其从一个地点运输到另一个地点的技术，以便将其作为消耗品提供给NMR研究人员;这将增加NMR的灵敏度，并使药物更快，更安全地推向市场。