A microreactor chip platform for quantitative analysis of unsaturated aldehydes in exhaled breath

项目名称： 用于呼气中不饱和醛定量分析的微反芯片平台 7.项目摘要/摘要 肺癌是所有癌症中死亡率最高的。早期发现肺癌是一个关键因素 提高肺癌患者的生存率。对呼气样本的分析具有巨大的潜力 成为肺癌早期检测的强大非侵入性筛查和诊断工具。一批 最近的出版物表明，呼气中的某些挥发性有机化合物(VOC)可能是 肺癌的代谢输出。然而，呼气VOCs的分析存在一些关键挑战， 阻碍了呼气分析技术在临床上的应用。这些挑战包括微量的 呼气中的VOCs远低于目前大多数分析仪器的检测下限； 对大量VOCs进行分选；以及大量和/或结构相似带来的基质干扰 与癌症无关的挥发性有机物。这些挑战使得识别肺的真实代谢标志物变得非常困难。 癌症。 我们已经开发了一种微反应器方法，它使用季胺氧涂层进行化学选择 捕获呼气中的羰基化合物。已确定四种羰基化合物具有 肺癌患者呼气中的浓度显著高于健康对照组 研究对象。然而，季胺氧涂层与不饱和醛的慢反应动力学 这些化合物的不稳定性质使得微反应器技术不足以量化 呼气中的关键不饱和醛。呼气中的许多不饱和醛与 肺癌功能障碍引起的氧化应激。不幸的是，目前还没有一种技术可以 用于充分测量呼气中的不饱和醛。 本项目的目标是开发一种用于定量分析的微反芯片平台技术。 呼气中不饱和醛在早期肺癌与良性肺癌鉴别诊断中的应用 结节。这项技术将克服当前呼气分析技术和 实现对不饱和醛的定量分析。这一目标将通过以下两个具体目标来实现 目的：具体目标1.开发一种新型的微反平台，用于不饱和气体的精确测量 呼气中的醛；特定目标2.建立呼吸诊断肺癌的新算法 分析。 拟议的用于不饱和醛定量分析的微反芯片平台将是 具有变革性，因为它将使测量和鉴定肺癌代谢醛和 建立一种非侵入性鉴别肺癌和肺良性结节的工具。这个 微反芯片实现呼气中不饱和醛的定量分析也可用于低 剂量CT筛查对早期肺癌的诊断及良、恶性肺癌的鉴别诊断 结节。拟议的技术将优于目前的呼气分析方法，因为有四个 关键创新：(1)通过定量测定癌症代谢不饱和来诊断肺癌 呼气中的醛；(2)减少样品排空时间的新型微反应器；(3)优化 用于有效捕获不饱和醛的化学选择涂层；以及(4)分析加合物的分离 并用超高效液相色谱-质谱法进行定量。

Project Title: A microreactor chip platform for quantitative analysis of unsaturated aldehydes in exhaled breath 7. Project Summary/Abstract Lung cancer has the highest mortality of all types of cancer. Early lung cancer detection is a key factor for increasing survival rates of lung cancer patients. The analysis of exhaled breath samples has great potential to become a powerful non-invasive screening and diagnostic tool for early lung cancer detection. A number of recent publications have indicated that certain volatile organic compounds (VOCs) in exhaled breath may be lung cancer metabolic output. However, there are some critical challenges for the analysis of breath VOCs that hinder the use of breath analysis technology for clinical applications. These challenges include trace levels of VOCs in breath much lower than the detection limits of most current analytical instruments; the complexity of sorting a large number of VOCs; and matrix interferences imparted by abundant and/or structurally similar VOCs unrelated to cancers. These challenges make it very difficult to identify true metabolic markers of lung cancers. We have developed a microreactor approach that uses a quaternary aminooxy coating for chemoselective capture of carbonyl compounds in exhaled breath. Four carbonyl compounds have been identified to have significantly higher concentrations in the breath of lung cancer patients than in the breath of healthy control subjects. However, the slow reaction kinetics of the quaternary aminooxy coating with unsaturated aldehydes and unstable nature of these compounds make the microreactor technology inadequate for quantification of key unsaturated aldehydes in exhaled breath. Many unsaturated aldehydes in exhaled breath are related to lung cancer dysfunction-induced oxidative stress. Unfortunately, there is no current technology that can be used to adequately measure unsaturated aldehydes in exhaled breath. The goal of this project is to develop a microreactor chip platform technology for quantitative analysis of unsaturated aldehydes in exhaled breath for differentiation of early lung cancer from benign pulmonary nodules. The technology will overcome all critical challenges of current breath analysis technologies and enable quantitative analysis of unsaturated aldehydes. The goal will be fulfilled by the following two specific aims: Specific Aim 1. Develop a novel microreactor platform for accurate measurement of unsaturated aldehydes in exhaled breath; Specific Aim 2. Establish novel algorithms for diagnosis of lung cancer by breath analysis. The proposed microreactor chip platform for quantitative analysis of unsaturated aldehydes will be transformative because it will enable measurement and identification of lung cancer metabolic aldehydes and establish a non-invasive tool for differentiation of lung cancer from benign pulmonary nodules. The microreactor chip enabled quantitative analysis of unsaturated aldehydes in breath can also be used with low dose CT screening for detection of early lung cancer and differentiation of lung cancer from benign pulmonary nodules. The proposed technology will be superior to current breath analysis approaches because of four critical innovations: (1) diagnosis of lung cancer by quantitative measurement of cancer metabolic unsaturated aldehydes in exhaled breath; (2) a novel microreactor for decreasing sample evacuation time; (3) optimized chemoselective coatings for efficient capture of unsaturated aldehydes; and (4) separation of analyte adducts and quantitation by UHPLC-MS.