基于呼出气微生物三维指纹图的呼吸系统感染快速检测方法的研究

项目名称： 基于呼出气微生物三维指纹图的呼吸系统感染快速检测方法的研究

项目编号： No.21477003

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 化学工业

项目作者： 要茂盛

作者单位： 北京大学

项目金额： 90万元

中文摘要： 呼吸系统感染每年造成几百万人的死亡，但其感染原因不明朗、且临床上缺乏快速诊断技术，无法保证患者得到及时正确的治疗。本项目主要通过利用荧光检测、高通量测序等方法研究空气及呼吸系统感染患者的呼出气等样品的微生物种群结构包括细菌、病毒与真菌；获得关键病原体清单，揭示呼吸暴露风险，实现感染的快速诊断分型。通过高通量测序研究是否存在细菌、病毒并发感染，以及细菌感染、病毒感染或真菌感染对呼吸系统固有种群结构的影响；研究利用荧光检测方法获得患者及健康人呼出气中活性微生物三维指纹图包括粒径、浓度与代谢活性来快速诊断呼吸系统感染，并研究其影响因素如呼气模式等；对比测序及血常规检测结果来验证该方法的有效性。研究结果将揭示引发呼吸系统感染的根本原因，为评价大气污染构成的呼吸系统感染风险提供科学依据，并为其临床诊断创建快速、廉价、无创的技术手段，从而更好地防范与治疗呼吸系统疾病，减少生命财产损失。

中文关键词： 生物气溶胶；呼出气；微生物3维指纹图；荧光检测；呼吸系统感染

英文摘要： Respiratory infections caused millions of deaths each year. However its infection reasons remain unkown and methods for their rapid and accurate clinical diagnosis are significantly lacking, thus the flu patients often fail to receive timely and proper treatment. This project is designed to study the microbial population structures of exhaled breath and other biological samples, to identify a list of key respiratory infection causing pathogens, to study respiratory exposure risks, and finally to achieve rapid detection of respiratory detection using next generation sequence and fluorescence detection method. Using high throughput gene sequence, this study is aimed to study if there exists co-infections of bacteria and viruses, and how the microbial population structure of the respiratory system is affected when an infection occurs. More importantly, fluorescence based bioaerosol sensor is also to be used to produce 3D microbial fingerprint including microbial size, concentration and metabolic activity for exhaled breath from both ill and healthy subjects, and the produced graphs tested under different expiratory modes are then used to discern among bacterial, viral and fungal infections. Finally,the developed technology is further verified using the data obtained through the high throuhput gene sequence and information from routine blood tests such as white blood cell count, neutrophil and hemoglobin. The results from this study are expected to reveal the fundamental reasons and mechanisms for respiratory infection,to provide important guidelines for evaluating the respiratory exposure risks from air pollution, and to provide rapid,cheap and non-invasive method for clinical diagnosis of respiratory infection.The information and technology developed from this proposed project are expected to better prevent and treat respiratory infections, thus reducing the loss of human life.

英文关键词： Bioaerosol;Exhaled breath;Microbial 3D Fingerprints;Fluorescence detection;Respiratory infection