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.

项目标题： 微反应器芯片平台，用于定量分析呼气呼吸中的不饱和醛 7。项目摘要/摘要 肺癌在所有类型的癌症中的死亡率最高。早期肺癌检测是 肺癌患者的存活率提高。呼出呼吸样品的分析具有很大的潜力 成为早期肺癌检测的强大的非侵入性筛查和诊断工具。许多 最近的出版物表明，呼气呼吸中某些挥发性有机化合物（VOC）可能是 肺癌代谢产量。但是，对于分析呼吸VOC的挑战， 阻碍呼吸分析技术用于临床应用。这些挑战包括痕量水平 呼吸中的VOC远低于大多数当前分析仪器的检测极限；复杂性 对大量VOC进行排序；和矩阵干扰，由丰富和/或结构相似 VOC与癌症无关。这些挑战使得很难识别肺的真正代谢标记 癌症。 我们已经开发了一种微反应器方法，该方法使用了第四纪氨基涂层进行化学选择性 捕获呼出的呼吸中的羰基化合物。已经确定了四种羰基化合物 肺癌患者呼吸的浓度明显高于健康对照的呼吸 主题。但是，与不饱和醛的第四纪氨基涂层的缓慢反应动力学 这些化合物的不稳定性使微反应器技术不足以量化 呼气的钥匙不饱和醛。呼气呼吸中的许多不饱和醛都与 肺癌功能障碍诱导的氧化应激。不幸的是，目前没有技术可以 用于在呼出的呼吸中充分测量不饱和醛。 该项目的目的是开发一种微反应器芯片平台技术，以定量分析 呼气的呼吸中的不饱和醛，以分化早期肺癌与良性肺的分化 结节。该技术将克服当前呼吸分析技术和 对不饱和醛的定量分析。以下两个特定的目标将实现目标 目的：特定目的1。开发一个新型的微反应器平台，以准确测量不饱和 呼气的醛;特定目的2。建立新的算法以通过呼吸诊断肺癌 分析。 提议的微反应器芯片平台用于定量分析不饱和醛的芯片平台将是 变革性，因为它将能够测量和鉴定肺癌代谢醛和 建立一种非侵入性工具，用于分化肺癌与良性肺结节。这 微反应器芯片启用了呼吸中不饱和醛的定量分析，也可以使用低 剂量CT筛查以检测早期肺癌和肺癌与良性肺的分化 结节。提议的技术将优于当前的呼气分析方法，因为四个 关键创新：（1）通过定量测量癌症代谢不饱和诊断肺癌 呼气的醛; （2）一种新型的微反应器，用于减少样品疏散时间； （3）优化 化学选择性涂层，可有效捕获不饱和醛； （4）分离物加合物的分离 和UHPLC-MS的定量。