This project combines exciting recent commercial advances in both multiflowcell NMR microprobe design and hyperpolarization of NMR samples. Concerning the former, the submitting organization now commercially offers NMR detection probes that contain multiple independent detection cells integrated into a single probe package to permit NMR detection of multiple independent samples taken directly from microvials and wellplates and using a single NMR superconducting magnet and spectrometer. Considering the latter, commercial polarization instrumentation has now become available to boost the inherent sensitivity of the NMR experiment by as much as 4 or 5 orders-of-magnitude over what is possible using standard Boltzmann polarization alone. The probe represents the heart of the NMR instrument, coupling the element of greatest value (the sample) to the hardware and software designed to extract information from the sample. This effort proposes the design and construction of a dual flowcell probe, where one detection cell is specifically tailored to hyperpolarized samples, and the other detection cell is dedicated to conventional laboratory samples, e.g. analytical fractions that originate from chromatography. The intended application market is human-health-related areas of research. Such areas typically are represented by an integrated workflow diagram where samples originate from chromatography, are analyzed by complementary platforms such as mass spectrometry (MS), evaporative light scattering detection (ELSD), ultraviolet (UV) detection, and a host of other analytical detectors that can now includes NMR. Relevant application areas include metabolomics and the study of human, animal, and plant metabolomes, natural products analysis and other forms of early drug lead discovery, and structure verification and library screening such as is employed routinely in the pharmaceutical and biological health industries. Although well-known for its information-rich qualities, NMR has lagged historically in its role due to poor sensitivity (e.g. long experimental times) relative to the other platforms mentioned. The probe resulting from this commercialization effort marries new generations of innovative and mass-sensitive probe design with striking advances in polarization enhancement to greatly reduce NMR acquisition times while fitting into modern analytical laboratory workflow via microvial- and wellplate-based sample formats. The timing of this new analytical tool dovetails with next-generation methodologies that have recently been reported, and that carry significantly increased need for comprehensive and multi-dimensional data to address complex biological problems, e.g. as represented by metabolomics. As such, this probe has high potential to significantly impact human health-related areas of scientific research.
Public Health Relevance: The commercial availability of a NMR probe that detects hyperpolarized samples and conventional samples adds another critical dimension to the scientific strategies employed over the past decade to enhance the measurement sensitivity of NMR, an analytical technique well-known for its information-rich qualities and inherent value to structural biology, pharmaceutical discovery, and to human health. Through the use of the detection probe described for development in this SBIR proposal, the integrated combination of DNP and conventional proton (1H{13C}) detection using a single magnet represents an analytical platform that can complement mass spectrometry, chromatography, and other optical-based platforms in the analytical and pharmaceutical laboratory. The need for, and the potential impact on human health resulting from new generations of NMR-based analyzers is extremely high.
Public Health Relevance: This Public Health Relevance is not available.
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