Tuesday, May 20, 2025
5/20/2025
MANUFACTURE AND SUPPLY OF HYPERPOLARIZED CHLOROFORM FOR USE AS AN NMR SOLVENT - 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.
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