Real-time measurement of CO₂ 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 ¹³CO₂, ¹²CO₂, and ¹⁸OC¹⁶O in exhaled breath by direct absorption spectroscopy, and then determining the ¹³CO₂/¹²CO₂ isotope ratio (δ¹³C) and ¹⁸OC¹⁶O/¹²CO₂ isotope ratio (δ¹⁸O). The HWG sensor showed a fast response time of 3 s. Continuous measurement of δ¹³C and δ¹⁸O in the standard CO₂ sample with known isotopic ratios for ∼2 h was performed. Precisions of 2.20‰ and 1.98‰ for δ¹³C and δ¹⁸O respectively at optimal integration time of 734 s were estimated from Allan variance analysis. Accuracy of −0.49‰ and −1.20‰ for δ¹³C and δ¹⁸O, 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 δ¹³C and δ¹⁸O, respectively, were obtained at the integration time of 0.54 s with the application of Kalman filtering. The concentrations of ¹²CO₂, ¹³CO₂ and ¹⁸OC¹⁶O in breath cycles were measured and processed by Kalman filtering in real time. The measured values of δ¹⁸O and δ¹³C 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 δ¹³C and δ¹⁸O values in breath samples and its potential for immediate respiratory monitoring and disease diagnosis.