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

呼出气中不饱和醛定量分析的微反应器芯片平台

• 批准号: 9768418
• 负责人: Xiao-An Fu
• 金额: $ 18.22万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-22 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9768418
• 关键词: 2-butenal; 4 hydroxynonenal; Acrolein; Adult; Affect; Aldehydes; Algorithms; Ammonium; Benign; Breath Tests; Cancer Patient; Centers for Disease Control and Prevention (U.S.); Charge; Cigarette; Detection; Diagnosis; Diagnostic; Diagnostic Sensitivity; Early Diagnosis; Exhalation; Functional disorder; Goals; Hexenal; High Pressure Liquid Chromatography; Human; Ketones; Kinetics; Lung nodule; Malignant Neoplasms; Malignant neoplasm of lung; Mass Spectrum Analysis; Measurement; Measures; Metabolic; Metabolic Marker; Modality; Nature; Non-Malignant; Output; Oxidative Stress; Patients; Phase; Process; Publications; Reaction; Sampling; Scanning; Sensitivity and Specificity; Silicon; Smoker; Smoking; Sodium Chloride; Sorting - Cell Movement; Specificity; Statistical Data Interpretation; Structure; Survival Rate; Technology; Time; X-Ray Computed Tomography; adduct; base; cancer type; carbonyl compound; clinical application; computed tomography screening; cost effective; diagnostic accuracy; innovation; innovative technologies; instrument; low-dose spiral CT; lung cancer screening; lung imaging; mortality; non-smoking; noninvasive diagnosis; novel; novel diagnostics; screening; success; tool; volatile organic compound

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.

项目名称： 呼出气中不饱和醛定量分析的微反应器芯片平台 7. 项目总结/摘要 肺癌是所有类型癌症中死亡率最高的。早期发现肺癌是关键因素 提高肺癌患者的生存率。呼出气样本的分析具有巨大的潜力 成为早期肺癌检测的强大无创筛查和诊断工具。一些 最近的出版物表明，呼出气中的某些挥发性有机化合物（VOC）可能是 肺癌代谢输出。然而，呼吸 VOC 分析存在一些关键挑战： 阻碍了呼吸分析技术的临床应用。这些挑战包括痕量水平 呼吸中的VOCs远低于大多数当前分析仪器的检测限；的复杂性 对大量VOC进行分选；以及由丰富和/或结构相似造成的基质干扰 与癌症无关的挥发性有机化合物。这些挑战使得识别肺部真正的代谢标志物变得非常困难 癌症。 我们开发了一种微反应器方法，使用季氨氧基涂层进行化学选择性 捕获呼出气中的羰基化合物。四种羰基化合物已被鉴定为 肺癌患者呼吸中的浓度显着高于健康对照者的呼吸中 科目。然而，季氨氧基涂层与不饱和醛的反应动力学缓慢 这些化合物的不稳定性质使得微反应器技术不足以量化 呼出气中的关键不饱和醛。呼出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，目前还没有技术可以 用于充分测量呼出气中的不饱和醛。 该项目的目标是开发一种微反应器芯片平台技术，用于定量分析 呼出气中的不饱和醛用于区分早期肺癌和良性肺癌 结节。该技术将克服当前呼吸分析技术的所有关键挑战 能够定量分析不饱和醛。具体目标将通过以下两个方面来实现 目标： 具体目标 1. 开发一种新型微反应器平台，用于精确测量不饱和脂肪酸 呼出气中的醛类；具体目标 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应器芯片平台将是 具有变革性，因为它将能够测量和识别肺癌代谢醛和 建立一种非侵入性工具来区分肺癌和良性肺结节。这 微反应器芯片能够定量分析呼吸中的不饱和醛，也可用于低浓度 剂量CT筛查用于检测早期肺癌并区分肺癌与良性肺癌 结节。所提出的技术将优于当前的呼吸分析方法，因为有四个 关键创新点：（1）通过定量测量癌症代谢不饱和状态诊断肺癌 呼出气中的醛类； (2)一种减少样品抽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性涂层； (4) 分析物加合物的分离 并通过 UHPLC-MS 进行定量。