LASER BASED 14C COUNTING FOR BIOMEDICAL STUDIES

用于生物医学研究的基于激光 14C 计数

• 批准号: 8362755
• 负责人: DANIEL E MURNICK
• 金额: $ 23.41万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362755
• 关键词: Algorithms; Amino Acid Sequence; Biomedical Research; C14 isotope; Calibration; Carbon; Carbon Dioxide; Cells; Complex; Detection; Devices; Diagnostic; Dose; Drug Kinetics; Electronics; Event; Funding; Gases; Goals; Grant; Image; Label; Laboratories; Lasers; Longitudinal Studies; Measurement; Measures; Medical; Medical Research; Methods; National Center for Research Resources; Noise; Nuclear Decay; Peptide Sequence Determination; Principal Investigator; Process; Radioactivity; Radioisotopes; Research; Research Infrastructure; Resource Development; Resources; Sample Size; Sampling; Signal Transduction; Source; System; Techniques; Technology Transfer; Tracer; United States National Institutes of Health; Variant; accelerator mass spectrometry; base; biological research; cost; design; digital; dosage; drug development; drug discovery; instrument; instrumentation; mass spectrometer; metabolic abnormality assessment; pressure; prototype; quantum; research facility; research study; seal; stable isotope; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The use of isotopic labeling with carbon 14 is widespread in biological and medical research, medical diagnostics and drug discovery and development. However, methods to detect radioisotopes depend on the detection of a nuclear decay event, an inefficient process as there is only 1 decay event per minute for every 4.35 billion atoms of 14C present in a sample,requiring the use of high levels of radioactivity. The aim of this project is to demonstrate a device, suitable for routine laboratory use, for atom counting of the tracer 14C, treating 14C as a "stable" isotope, decreasing the dosage required for most experiments and making new classes of studies possible. LARA will be extended from analysis of 13CO2 to similar analysis of 14CO2. Instrumentation will have sensitivity orders of magnitude greater than possible with scintillation (decay) detection and will compete with typical tandem accelerator mass spectrometers (AMS) that have demonstrated sensitivity at the picomole to the attomole level. The enhanced sensitivity is important for low dose and small sample tracer studies, long-term metabolic studies, pharmacokinetics studies and is being studied as a possible tool for protein sequencing and micro-imaging studies. A 14CO2 LARA device is projected to be considerably smaller, less complex and much lower in cost than an AMS with comparable capability. It will be shown that a sealed infrared laser operating at a unique infrared transition in 14CO2, can be routinely used to probe a sample cell containing carbon dioxide. The sample will be in a low pressure electrical discharge optimized for low noise detection of the optogalvanic effect. Such a system can be used to quantitatively measure small samples of 14C-enriched carbon dioxide. Results of the measurements with enriched samples will quantify improvements required to achieve ultimate sensitivity. Techniques will be developed to achieve enhanced sensitivity at the picomole to attomole level. Techniques will include electronic and digital algorithms to lower noise, gas mixture variations to enhance signal and quantum electronic (laser) enhancements. It is further aimed to build prototype instruments for routine laboratory use and transfer the technology to biomedical research facilities. Major progress in the last year led to exceeding design goals and achieving sensitivity of order 10-15 14C/12C ratio with sample size of order 5 to 10 micrograms total carbon . Calibration samples obtained from the Research Resource for Biomedical AMS have been used in these studies.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 在生物学和医学研究，医学诊断以及药物发现与开发中，同位素标记与碳14的使用普遍存在。但是，检测放射性同位素的方法取决于检测核衰减事件，这是一种效率低下的过程，因为样品中每分钟只有43.5亿个14C原子每分钟只有1个衰减事件，需要使用高水平的放射性。 该项目的目的是展示适合常规实验室使用的设备，用于原子计数14C的原子计数，将14C视为“稳定”同位素，减少了大多数实验所需的剂量，并使新的研究类别成为可能。 LARA将从13CO2的分析扩展到对14CO2的类似分析。通过闪烁（衰减）检测，仪器的灵敏度阶将比可能的数量级大，并将与典型的串联加速器质谱器（AMS）竞争，这些质谱仪（AMS）在Picomole对attomole水平上表现出灵敏度。增强的敏感性对于低剂量和小样品示踪剂研究，长期代谢研究，药代动力学研究至关重要，并且正在研究作为蛋白质测序和微影像研究的可能工具。 14CO2 LARA设备预计比具有可比能力的AMS小得多，复杂且成本要低得多。可以证明，在14CO2中以唯一的红外过渡运行的密封红外激光器可以通常用于探测含有二氧化碳的样品单元。样品将处于优化的低压电排放中，以低噪声检测光能效应。这样的系统可用于定量测量富含14C二氧化碳的小样品。使用富集样品的测量结果将量化实现最终灵敏度所需的改进。将开发技术以提高脚步对阿托莫尔水平的灵敏度。技术将包括电子和数字算法对较低的噪声，气体混合物的变化，以增强信号和量子电子（激光）增强功能。它进一步旨在建立原型工具，以常规实验室使用，并将技术转移到生物医学研究设施中。 去年的重大进展导致超出设计目标，并达到10-15 14C/12C比率的灵敏度，其样本量为5至10微克总碳。 从生物医学AM的研究资源获得的校准样品已在这些研究中使用。