A Ppb-level MIR-PAS for ¹²CO₂/¹³CO₂ isotope analysis toward on-line breath-based H. pylori sensing

Helicobacter pylori infection is closely associated with chronic gastritis, peptic ulcers, and gastric cancer, rendering rapid and noninvasive diagnostic technologies clinically essential. Current breath tests, such as the ¹³C-urea breath test (¹³C-UBT), typically rely on breath collection bags followed by offline analysis, which limits real-time monitoring capabilities. To overcome this constraint, we presented a mid-infrared photoacoustic spectroscopy (MIR-PAS) system for real-time detection of CO₂ isotopes and evaluation of ¹³C-UBT responses. A dual-channel differential resonant photoacoustic cell (DPAC) with a minimal sample volume of 10.3 mL was designed to enhance acoustic signal collection, achieving a resonance frequency of 3775.7 Hz and a Q-factor of 27. Target absorption lines of ¹²CO₂ (2299.64 cm^-¹) and ¹³CO₂ (2299.80 cm^-¹) were selected within the strong ν₃ band to ensure high-resolution isotopic discrimination using a 4.35 μm quantum cascade laser. The sensor demonstrated excellent linear response (R² > 0.994) across 500-2500 ppm and achieved detection limits of 8.98 ppb for ¹²CO₂ and 2.81 ppb for ¹³CO₂ with the optimal averaging. δ¹³C measurements exhibited a precision of 0.066 ‰ at 76 s averaging time. Breath-sampling tests further revealed distinct temporal release patterns of CO₂ isotopes during exhalation. These results confirmed that the developed MIR-PAS system provides a compact, sensitive, and robust platform for isotopic CO₂ analysis and demonstrates strong potential for point-of-care H. pylori diagnostics.