Dual Flowcell Detection Probe for Nuclear Magnetic Resonance Detection of Convent

描述（由申请人提供）：该项目结合了最近在多流池核磁共振微探针设计和核磁共振样品超极化方面令人兴奋的商业进展。关于前者，提交组织现在提供商业核磁共振检测探针，该探针包含多个独立的检测单元集成到一个探针包中，允许使用单个核磁共振超导磁体和光谱仪直接从微瓶和井板中提取多个独立样品进行核磁共振检测。考虑到后者，商业极化仪器现在已经可用来提高核磁共振实验的固有灵敏度，比单独使用标准玻尔兹曼偏振可能提高的灵敏度高达4或5个数量级。探针代表了核磁共振仪器的心脏，将最有价值的元素（样品）与设计用于从样品中提取信息的硬件和软件耦合在一起。这项工作提出了双流池探针的设计和构建，其中一个检测池专门用于超极化样品，另一个检测池专门用于常规实验室样品，例如来自色谱的分析分数。预期的应用市场是与人类健康有关的研究领域。这些区域通常由一个集成的工作流图表示，其中样品来自色谱，通过互补平台进行分析，如质谱（MS），蒸发光散射检测（ELSD），紫外线（UV）检测，以及许多其他分析检测器，现在可以包括核磁共振。相关的应用领域包括代谢组学和人类、动物和植物代谢组学的研究，天然产物分析和其他形式的早期药物先导物发现，以及结构验证和文库筛选，如在制药和生物健康行业中常规使用的。尽管NMR以其信息丰富的特性而闻名，但相对于上述的其他平台，由于灵敏度差（例如实验时间长），它在历史上一直落后于它的作用。这种商业化的探针结合了新一代的创新和质量敏感的探针设计，在极化增强方面取得了惊人的进步，大大减少了核磁共振采集时间，同时通过微瓶和井板样品格式适应现代分析实验室工作流程。这种新的分析工具的时机与最近报道的下一代方法相吻合，并且对全面和多维数据的需求显着增加，以解决复杂的生物学问题，例如以代谢组学为代表。因此，该探针具有很大的潜力，可以显著影响与人类健康相关的科学研究领域。

DESCRIPTION (provided by applicant): 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.