Real-time measurement of CO isotopologue ratios in exhaled breath by a hollow waveguide based mid-infrared gas sensor.

A hollow waveguide (HWG) based mid-infrared gas sensor using a 2.73 µm distributed feedback (DFB) laser was developed for simultaneously measuring the concentration changes of the three isotopologues CO, CO, and OCO in exhaled breath by direct absorption spectroscopy, and then determining the CO/CO isotope ratio (δC) and OCO/CO isotope ratio (δO). The HWG sensor showed a fast response time of 3 s. Continuous measurement of δC and δO in the standard CO sample with known isotopic ratios for ∼2 h was performed. Precisions of 2.20‰ and 1.98‰ for δC and δO respectively at optimal integration time of 734 s were estimated from Allan variance analysis. Accuracy of -0.49‰ and -1.20‰ for δC and δO, respectively, were obtained with comparison to the values of the reference standard. The Kalman filtering method was employed to improve the precision and accuracy of the HWG sensor while maintaining high time resolution. Precision of 5.45‰ and 4.88‰ and the accuracy of 0.21‰ and -1.13‰ for δC and δO, respectively, were obtained at the integration time of 0.54 s with the application of Kalman filtering. The concentrations of CO, CO and OCO in breath cycles were measured and processed by Kalman filtering in real time. The measured values of δO and δC in exhaled breath were estimated to be -21.35‰ and -33.64‰, respectively, with the integration time of 1 s. This study demonstrates the ability of the HWG sensor to obtain δC and δO values in breath samples and its potential for immediate respiratory monitoring and disease diagnosis.