Tritum AMS Analysis of Cancer Biomarkers

癌症生物标志物的 Tritum AMS 分析

• 批准号: 6783857
• 负责人: Paul L Skipper
• 金额: $ 32.47万
• 依托单位: NEWTON SCIENTIFIC, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-27 至 2007-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6783857
• 关键词: animal tissue; bioengineering /biomedical engineering; biomarker; biomedical equipment development; carcinogenesis; clinical biomedical equipment; electrospray ionization mass spectrometry; fluid flow; high performance liquid chromatography; high throughput technology; mass spectrometry; molecular oncology; particle accelerators; tritium

DESCRIPTION (provided by applicant): The goal of this Phase II STTR program is to develop a high-throughput, ultra-sensitive accelerator mass spectrometer for the detection and quantification of tritium in labeled biological molecules. Accelerator mass spectrometry (AMS) is a highly selective means for detecting tritium that can achieve a measurement sensitivity over 1000 times greater than decay counting. Existing AMS instruments capable of measuring tritium are designed to also measure 14C and other higher mass isotopes. However, significant advantages accrue to an AMS system dedicated to the measurement of tritium. One advantage is greatly reduced instrument size and cost. A second, and perhaps even more important advantage, is high sample throughput. The low natural abundance of 3H, which is more than 1000 times lower than that of 14C, means that smaller absolute quantities and concentrations of tritium can be detected in labeled samples with equal measurement accuracy. Consequently, tritium AMS can be used in conjunction with very small volume, high-throughput microfluidic sample processing systems. A unique feature of the proposed system is integration of the AMS with interfaces that permit rapid, direct introduction of discrete samples as well as continuous-flow monitoring of chromatography. The resulting design lends itself to high-throughput applications that are inaccessible to conventional AMS approaches. In Phase I we demonstrated detection of 3H-labeled solution samples at very low energy using an existing dual-isotope biomedical AMS instrument. This work has allowed us to design an AMS instrument that is truly comparable in size and cost to other major laboratory analytical instruments, but that provides the unique capabilities of AMS for detection of extremely small quantities and concentrations of 3H-labeled compounds. In Phase II, we will design, fabricate and test a dedicated 3H-AMS instrument with sample introduction interfaces for both continuous sample injection via HPLC, as well as rapid introduction of discrete samples via microfluidic technologies. The resulting integrated systems will provide dramatic improvements in sample throughput, speed of analysis, and measurement sensitivity compared with presently available analytical instruments. This program is a collaboration between Newton Scientific, Inc., and the Biological Engineering Division at the Massachusetts Institute of Technology.

描述（由申请人提供）：此II期STTR计划的目标是开发高通量，超敏感的加速器质谱仪，用于检测和定量标记的生物分子中的tri曲。加速器质谱法（AMS）是一种高度选择性的手段，用于检测可以达到测量敏感性超过1000倍以上的tri剂量，而不是衰减计数。现有的AMS仪器旨在测量trium，还可以测量14C和其他较高的质量同位素。但是，专门用于测量tritium的AMS系统具有显着优势。一个优点是仪器的尺寸和成本大大降低。一秒钟，甚至更重要的优势是高样本吞吐量。 3H的低自然丰度比14C低1000倍，这意味着在具有相等的测量精度的标记样品中可以检测到较小的绝对量和浓度。因此，tritium ams可以与非常小的高通量微流体样品处理系统结合使用。该系统的一个独特功能是将AM与接口集成在一起，该接口可以快速直接引入离散样品以及色谱的连续流量监测。由此产生的设计将自己适用于常规AMS方法无法访问的高通量应用程序。 在第一阶段，我们证明了使用现有的双相同位素生物医学AMS仪器在非常低的能量下检测到3H标记的溶液样品。这项工作使我们能够设计一种与其他主要实验室分析仪器的尺寸和成本相当的AMS仪器，但它为检测到极少量和浓度的3H标记化合物提供了AMS的独特功能。在第二阶段，我们将设计，制造和测试专用的3H-AMS仪器，并带有样品引入界面，用于通过HPLC进行连续样品注射，并通过微流体技术快速引入离散样品。与目前可用的分析仪器相比，所得的集成系统将在样品吞吐量，分析速度和测量敏感性方面具有显着改善。该计划是牛顿科学公司与马萨诸塞州理工学院的生物工程部门之间的合作。