Dual Flowcell Detection Probe for Nuclear Magnetic Resonance Detection of Convent

用于Convent核磁共振检测的双流通池检测探针

• 批准号: 7538113
• 负责人: TIMOTHY L PECK
• 金额: $ 10万
• 依托单位: PROTASIS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2009-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7538113
• 关键词: Acetone; Address; Agreement; Aliquot; Animals; Area; Be++ element; Beryllium; Biological; Biological Factors; Biological Markers; Blood capillaries; Businesses; Bypass; Categories; Cell Nucleus; Cells; Chromatography; Class; Complement; Complex; Confidentiality; Coupling; Data; Data Quality; Detection; Development; Dimensions; Elements; Employee Strikes; Evaluation; Family; Funding; Gases; Generations; Goals; Government; Health; Heart; Heating; Human; Industry; Investigation; Laboratories; Lead; Length; Letters; Libraries; Liquid substance; Marketing; Mass Spectrum Analysis; Measurement; Methodology; Noise; Nuclear; Nuclear Magnetic Resonance; Numbers; Optics; Performance; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I Clinical Trials; Plants; Process; Protons; Public Health; Purpose; RF coil; Relative (related person); Reporting; Research; Resolution; Role; Sampling; Scanning; Screening procedure; Signal Transduction; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Software Design; Solutions; Solvents; Standards of Weights and Measures; Structure; Sucrose; Support System; System; Techniques; Technology; Text; Thermodynamics; Time; Tube; United States National Institutes of Health; Vendor; analytical tool; base; capillary; commercialization; concept; design; design and construction; desire; detector; electric impedance; falls; high sensitivity probe; innovation; instrument; instrumentation; light scattering; magnetic field; metabolomics; next generation; pressure; research and development; research study; structural biology; ultraviolet

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.

描述（由申请人提供）：该项目结合了令人兴奋的多流动池NMR微探针设计和NMR样品超极化的最新商业进展。关于前者，提交组织现在商业上提供NMR检测探针，其包含集成到单个探针包中的多个独立检测单元，以允许直接从微瓶和孔板中取出的多个独立样品的NMR检测，并使用单个NMR超导磁体和分光计。考虑到后者，商业偏振仪器现在已经变得可用于将NMR实验的固有灵敏度提高多达4或5个数量级，而不是单独使用标准玻尔兹曼偏振。探头代表NMR仪器的心脏，将最有价值的元素（样品）连接到硬件和软件，旨在从样品中提取信息。这项工作提出了双流通池探针的设计和构造，其中一个检测池专门针对超极化样品定制，另一个检测池专用于常规实验室样品，例如源自色谱的分析级分。预期的应用市场是与人类健康相关的研究领域。这些领域通常由集成的工作流程图表示，其中样品来自色谱法，通过互补平台进行分析，例如质谱法（MS），蒸发光散射检测（ELSD），紫外（UV）检测和许多其他分析检测器，现在可以包括NMR。相关的应用领域包括代谢组学和人类、动物和植物代谢组的研究，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，例如在制药和生物健康行业中常规使用的。虽然以其信息丰富的品质而闻名，但由于相对于所提到的其他平台的灵敏度差（例如实验时间长），NMR在历史上一直落后于其作用。这项商业化努力产生的探针将新一代创新和质量敏感的探针设计与极化增强方面的显着进步结合在一起，大大缩短了核磁共振采集时间，同时通过基于微瓶和孔板的样品格式适应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道的下一代方法学相吻合，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，例如代谢组学。因此，该探测器有很大的潜力对人类健康相关的科学研究领域产生重大影响。 公共卫生关系：检测超极化样品和常规样品的NMR探针的商业可用性为过去十年中采用的科学策略增加了另一个关键维度，以提高NMR的测量灵敏度，NMR是一种以其信息丰富的质量和固有价值而闻名的分析技术结构生物学，药物发现和人类健康。通过使用SBIR提案中描述的检测探针，使用单个磁体的DNP和常规质子（1H{13 C}）检测的集成组合代表了一种分析平台，可以补充分析和制药实验室中的质谱、色谱和其他基于光学的平台。对新一代NMR分析仪的需求及其对人类健康的潜在影响非常高。