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: 8171682
• 负责人: DANIEL E MURNICK
• 金额: $ 0.85万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171682
• 关键词: Algorithms; Amino Acid Sequence; Biological; Biomedical Research; C14 isotope; Calibration; Carbon; Carbon Dioxide; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; Detection; Development; Devices; Diagnostic; Dose; Drug Kinetics; Electronics; Event; Funding; Gases; Goals; Grant; Image; Institution; Label; Laboratories; Lasers; Longitudinal Studies; Measurement; Measures; Medical; Medical Research; Methods; Noise; Nuclear Decay; Peptide Sequence Determination; Process; Radioactivity; Radioisotopes; Research; Research Personnel; Resources; Sample Size; Sampling; Signal Transduction; Source; System; Techniques; Technology Transfer; Tracer; United States National Institutes of Health; Variant; base; cost; design; digital; dosage; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 碳 14 同位素标记广泛应用于生物和医学研究、医学诊断以及药物发现和开发中。然而，检测放射性同位素的方法依赖于检测核衰变事件，这是一个低效的过程，因为样品中每 43.5 亿个 14C 原子每分钟只有 1 个衰变事件，需要使用高水平的放射性。 该项目的目的是展示一种适合常规实验室使用的装置，用于示踪剂 14C 的原子计数，将 14C 视为“稳定”同位素，减少大多数实验所需的剂量，并使新类别的研究成为可能。 LARA 将从 13CO2 的分析扩展到 14CO2 的类似分析。仪器的灵敏度将比闪烁（衰变）检测高出几个数量级，并将与典型的串联加速器质谱仪（AMS）竞争，后者已证明了皮摩尔至阿托摩尔水平的灵敏度。增强的灵敏度对于低剂量和小样本示踪剂研究、长期代谢研究、药代动力学研究非常重要，并且正在研究作为蛋白质测序和显微成像研究的可能工具。与具有同等功能的 AMS 相比，14CO2 LARA 设备预计体积要小得多，复杂性要低得多，成本也要低得多。它将证明，在 14CO2 中以独特的红外跃迁运行的密封红外激光器可常规用于探测含有二氧化碳的样品池。样品将处于低压放电状态，优化用于光电效应的低噪声检测。这样的系统可用于定量测量富含14C的二氧化碳的小样本。富集样品的测量结果将量化实现最终灵敏度所需的改进。将开发技术以实现皮摩尔至阿托摩尔水平的增强灵敏度。技术将包括用于降低噪声的电子和数字算法、用于增强信号的气体混合物变化以及量子电子（激光）增强。它还旨在建造供日常实验室使用的原型仪器，并将技术转移到生物医学研究设施。 去年取得的重大进展超出了设计目标，并实现了 10-15 14C/12C 比率的灵敏度，样本量为 5 至 10 微克总碳。 这些研究中使用了从生物医学 AMS 研究资源获得的校准样本。