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.