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

描述(申请人提供)：阻碍核磁共振应用范围的一个关键问题是其固有的低信噪比(SNR)。这将核磁共振研究局限于对相对较高浓度(毫米范围)的样品的研究。已经开发了一系列产品来提高在核磁共振实验中可获得的信噪比。例如，低温探头、磁感头、微线圈和磁场越来越大的磁体。超极化原子核可以产生10,000或以上的信噪比增强因子。这种信号的巨大增强使研究浓度水平在5米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。含有自旋非零的原子核的样品被置于“蛮力”条件(BF)中，即非常高的磁场(通常是B&gt；10特斯拉)和非常低的温度(通常是T&lt；100 MK)--将实现非常高的核极化。到目前为止，使用这种技术制造超极化材料的一个缺点是，在BF条件下，原子核松弛到磁平衡所需的时间很长。我们将采用“量子弛豫开关”(QRS)技术，允许原子核在低温环境中快速松弛，然后升温到室温，而不会损失过多的极化。这项技术的一个吸引人的特点是，它不需要向样品中添加自由基或催化剂来超极化。这是一种可扩展的方法，适用于所有非零自旋核--特别是在核磁共振实验中通常用作溶剂的氯仿和其他液体，和/或模拟体内某些条件，以便更好地研究各种蛋白质和多肽的行为。超极化溶剂将通过将极化传递到被分析的溶质来增加核磁共振实验的价值。这将消除对庞大而昂贵的资本设备的需求，以实现样品的超极化。此外，由于超极化溶剂在使用前被加热，样品不需要暴露在神秘的物理条件下即可超极化。我们的长期目标是为核磁共振市场制造和供应HP溶剂。我们的短期目标是证明HP氯仿可以用来增强来自溶质的核磁共振信号。为了实现这些目标，我们将实现以下具体目标：一、生产高比表面积冷冻氯仿粉末。证明QRS可以用来在冷冻粉状氯仿中产生至少1%的偏振。证明超极化可以在冰冻的氯仿中维持数小时或更长时间。IV表明，在室温下，HP氯仿可以用来增强来自溶质的核磁共振信号。 与公共健康相关：核磁共振用于分析药物和蛋白质的分子结构，但其速度和灵敏度因其固有的低噪声信号而受到限制。超极化样品可以将核磁共振实验中可获得的信号提高多达10,000倍。MKT已经开发了一种技术，可以使各种材料(特别是核磁共振实验中常用的氯仿等材料)超极化，并将它们从一个地点运送到另一个地点，以便作为消耗品提供给核磁共振研究人员；这将提高核磁共振的灵敏度，使药物能够更快、更安全地推向市场。

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.