Rapid photoacoustic trace gas sensor for online end-tidal CO monitoring in exhaled breath

Online detection of exhaled breath biomarkers has attracted increasing attention because of its noninvasive, real-time, and point-of-care diagnostic potential. End-tidal carbon monoxide (ETCO) is an important breath biomarker associated with smoking behavior, neonatal hemolysis, and cardiovascular diseases. Here, we report a differential photoacoustic spectroscopy (PAS) sensor for rapid and highly sensitive online ETCO monitoring. A compact 3D-printed dual-channel differential resonant photoacoustic cell (DPAC), with an effective sample volume of only 2.5 mL, was developed to enhance acoustic signal collection while suppressing common-mode noise. The optimized DPAC exhibited an acoustic resonance frequency of 3726.94 Hz, corresponding to a laser current modulation frequency of 1863.47 Hz for second-harmonic detection, with a quality factor of 26. A quantum cascade laser targeting the CO absorption line at 2176.1 cm -1 was used as the excitation source. The sensor exhibited excellent linearity over the concentration range of 0 - 1000 ppm, with an R 2 value exceeding 0.9979, enabling both ambient-level and highly elevated CO measurements on a single platform. A detection limit of 30.6 ppb was achieved at a lock-in time constant of 1 s. Breath measurements from five smokers and five non-smokers showed clear discrimination between the two groups. The smokers exhibited an average ETCO concentration of 21.4 ppm, with all measured values higher than 13.2 ppm, whereas the non-smokers showed an average ETCO concentration of 3.3 ppm, with a maximum value below 3.8 ppm. The proposed PAS sensor combines ppb-level sensitivity and a wide dynamic range, providing a promising platform for real-time breath analysis and preliminary ETCO monitoring.