SUMMARY

Human exhaled breath has gathered significant interest among scientists and researchers as a promising non-invasive method for diagnosing and monitoring patient conditions. Past research studies have demonstrated that human exhaled breath contains thousands of organic compounds originating from human metabolism, viruses, bacteria, and cell activity. Therefore, these compounds hold promise as potential biomarkers for dietary monitoring, cancer detection, and pathogen activity detection of a patient. Nevertheless, direct detection of these compounds from human breath is challenging due to several reasons such as the overwhelming presence of water vapor in the sample and very low (trace-level) concentrations of the target compounds themselves, causing the necessity of the exhaled breath sample preconditioning before measurement. This thesis aims to develop a device and framework encompassing all necessary components and steps for trace-level biomarker detection in human exhaled breath. The thesis comprises three proposed studies: The first study focuses on developing a breath collection device capable of collecting a preconcentrated gas-phase exhaled breath sample while simultaneously separating and collecting the water vapor (exhaled breath condensate) component. The device is designed to ensure patient comfort, portability, disposability, and compliance with standards for respiratory devices. In the second study, a non-targeted (exploratory) analysis is carried to obtain a comprehensive list of organic compounds present in both the preconcentrated gas-phase breath sample (VOC) and the liquid-phase exhaled breath condensate (EBC). State-of-the-art GCxGC-MS and HPLC systems are employed for the measurement and analysis of the VOC and EBC samples, respectively. A framework for the compound identification process is developed to minimize errors and compound misidentification during the process. For the third study, we aim to develop an electrochemical-based MEMS biosensor to target specific biomarkers found in human breath. The objectives are to design a low-cost and robust biosensor that can be seamlessly integrated with the portable breath collection system. The design framework developed in this study is expected to facilitate future sensor design processes for other exhaled breath biomarkers.