Executive Summary : | Chronic obstructive pulmonary disease (COPD) is a significant life¬ threatening lung disease that has caused morbidity and mortality across the globe. COPD is projected to be ranked the 7th major cause of chronic morbidity worldwide in 2030. The primary cause of COPD is exposure to tobacco smoke, and other risk factors include exposure to indoor and outdoor air pollution and fumes. A spirometry test confirms a COPD diagnosis but provides limited and indirect information about the actual degree of inflammation in the lower airways. Assessing airway inflammation in children younger than eight years of age calls for a more sophisticated diagnostic tool. Alternatively, human breath has always been a matrix of interest for disease diagnostics and monitoring due to its inherently non-invasive access. Nitric oxide in exhaled breath (eNO) has been identified as a biomarker of airway inflammation in COPD. The exhaled breath (EB) matrix predominantly comprises CO2, H2O, O2, and N2 next to much lower concentrated VOCs, which may mask the presence of biomarkers such as eNO for specific detection techniques. Hence, there is a requirement for analysis techniques with increased sensitivity and selectivity for identifying disease-related biomarkers against the breath matrix background. Moreover, the need for point-of-care (POC) medical instrumentation has drawn increasing attention to laser spectroscopic-based non-invasive human exhale analysis during the last decades since the development of new mid-infrared (MIR) laser sources. POC instruments can be developed to monitor exhaled breath with high accuracy, sensitivity, detection limits, and reasonable prices. A wide variety of biomarkers in EB have fundamental transitions in the MIR spectral regime. Recent advances in Hollow-Core Waveguide (HCW) technology in this region (3-20 µm) can facilitate the development of highly compact and sensitive trace gas sensing devices with potential usage in POC scenarios. However, for higher sensitivities, the length of the HCW may be increased, and bending the fiber for maintaining a compact footprint will cause optical losses. Alternatively, applying photoacoustic interferometry (PTI) may limit the length of the waveguide while simultaneously increasing the system's sensitivity. Moreover, combining PTI with substrate-integrated hollow waveguides based on a layered structure with the light-guiding channels integrated into a rigid solid-state substrate material bending losses seen in conventional HCW are avoided. Furthermore, these structures essentially act as gas cells, so faster data acquisition speeds can be expected. Hence this proposal will develop a 3D printed substrate integrated HCW based photoacoustic interferometry for NO measurements in exhaled breath matrix. |