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

描述（由申请人提供）：阻碍核磁共振（NMR）应用范围的一个关键问题是其固有的低信噪比（SNR）。这限制了核磁共振对相对高浓度（mM范围）样品的研究。为了提高核磁共振实验中可获得的信噪比，已经开发了一系列的产品。例子包括低温探针、敏感插头、微线圈和磁场越来越大的磁铁。超极化核可以产生10,000或更多的信噪比增强因子。这种巨大的信号增强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，消除了对信号平均的需要。含有非零自旋原子核的样品置于“蛮力”条件下（BF）。例如，非常高的磁场（通常为B bbb10特斯拉）和非常低的温度（通常为T < 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“量子松弛开关”（QRS）技术，该技术允许原子核在低温环境中快速松弛，然后加热到室温，而不会失去过多的极化。这种技术的一个吸引人的特点是，它不需要向样品中添加自由基或催化剂来使其超极化。这是一种可扩展的方法，适用于所有非零自旋核，特别是氯仿和其他液体，通常用作NMR实验和/或模拟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。超极化溶剂通过将极化转移到被分析的溶质上，将增加核磁共振实验的价值。这将消除对庞大和昂贵的资本设备的需要，以超极化样品。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氯仿可以用来增强溶质的核磁共振信号。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。2。证明QRS可用于在冷冻粉末状氯仿中产生至少1%的极化。3。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氯仿可用于增强室温下溶质的核磁共振信号。

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.