Breath-by-breath measurement of exhaled ammonia by acetone-modifier positive photoionization ion mobility spectrometry via online dilution and purging sampling

Exhaled ammonia (NH₃) is an essential noninvasive biomarker for disease diagnosis. In this study, an acetone-modifier positive photoionization ion mobility spectrometry (AM-PIMS) method was developed for accurate qualitative and quantitative analysis of exhaled NH₃ with high selectivity and sensitivity. Acetone was introduced into the drift tube along with the drift gas as a modifier, and the characteristic NH₃ product ion peak of (C₃H₆O)₄NH₄⁺ (K₀ = 1.45 cm²/V·s) was obtained through the ion-molecule reaction with acetone reactant ions (C₃H₆O)₂H⁺ (K₀ = 1.87 cm²/V·s), which significantly increased the peak-to-peak resolution and improved the accuracy of exhaled NH₃ qualitative identification. Moreover, the interference of high humidity and the memory effect of NH₃ molecules were significantly reduced via online dilution and purging sampling, thus realizing breath-by-breath measurement. As a result, a wide quantitative range of 5.87-140.92 μmol/L with a response time of 40 ms was achieved, and the exhaled NH₃ profile could be synchronized with the concentration curve of exhaled CO₂. Finally, the analytical capacity of AM-PIMS was demonstrated by measuring the exhaled NH₃ of healthy subjects, demonstrating its great potential for clinical disease diagnosis.