Dual Flowcell Detection Probe for Nuclear Magnetic Resonance Detection of Convent

描述(由申请人提供)：该项目结合了在多流细胞核磁共振微探针设计和核磁共振样品超极化方面令人振奋的最新商业进展。关于前者，提交组织现在商业化地提供包含多个独立检测单元的核磁共振检测探头，该探头被集成到单个探针组件中，以允许使用单个核磁共振超导磁体和光谱仪对直接从微瓶和井板获取的多个独立样品进行核磁共振检测。考虑到后者，商业偏振仪器现在已经可以将核磁共振实验的固有灵敏度提高多达4到5个数量级，而不是仅使用标准玻尔兹曼偏振。探头代表了核磁共振仪器的核心，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动池探头的设计和构造，其中一个检测池专门针对超极化样品量身定做，而另一个检测池专用于常规实验室样品，例如来自层析的分析馏分。预期的应用市场是与人类健康相关的研究领域。这些区域通常由一个集成的工作流程图表示，其中样品来自层析，由补充平台进行分析，例如质谱仪(MS)、蒸发光散射检测(ELSD)、紫外线(UV)检测以及现在可以包括核磁共振的许多其他分析检测器。相关的应用领域包括代谢组学和人类、动物和植物代谢物的研究，天然产物分析和其他形式的早期药物先导发现，以及结构验证和文库筛选，如制药和生物健康行业中常规使用的结构验证和文库筛选。尽管核磁共振以其信息丰富的特性而闻名，但由于与所提到的其他平台相比，其灵敏度较差(例如，较长的实验时间)，其作用在历史上一直落后。这一商业化努力产生的探头将新一代创新和质量敏感探头设计与极化增强方面的显著进步结合在一起，大大减少了核磁共振采集时间，同时通过基于微瓶和井板的样品格式适合现代分析实验室工作流程。这一新的分析工具的时机与最近报告的下一代方法相吻合，这些方法显著增加了对全面和多维数据的需求，以解决复杂的生物学问题，例如代谢组学所代表的问题。因此，这一探测极有可能对与人类健康相关的科学研究领域产生重大影响。 与公共健康相关：检测超极化样品和常规样品的核磁共振探头的商用为过去十年为提高核磁共振测量灵敏度而采用的科学战略增加了另一个关键维度，核磁共振是一种分析技术，以其信息丰富的性质和对结构生物学、药物发现和人类健康的内在价值而闻名。通过使用本SBIR提案中描述的检测探针，使用单个磁体的DNP和传统质子(1H{13C})检测的集成组合代表了一个分析平台，可以补充分析和药物实验室中的质谱学、层析和其他基于光学的平台。对基于核磁共振的新一代分析仪的需求及其对人类健康的潜在影响是非常高的。

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.