Multi-species breath biomarker profiling with an ultra-broadband (2.9-11.5 μm) spectroscopic platform

Abstract

Online, comprehensive molecular profiling of exhaled breath provides a non-invasive window into human metabolism, yet current optical platforms are restricted by narrow instantaneous spectral coverage. Here, we present a novel ultra-broadband mid-infrared spectroscopic platform that enables simultaneous, high-sensitivity detection of a comprehensive profile of breath biomarkers. By integrating an intrapulse difference-frequency generation (IDFG) supercontinuum source spanning 2.9-11.5 $μ$m (2580 cm$^{-1}$) with a custom-built Fourier transform spectrometer, we achieve a spectral resolution of 0.1 cm$^{-1}$ - surpassing current laser-based approaches. Combined with a standardized online sampling system, the platform achieves sensitivities in the tens of parts per billion over three minutes, resolving dynamic metabolic changes of ammonia, methane, isoprene, acetone, carbon monoxide, and nitrous oxide. We demonstrate the system's utility through proof-of-concept case studies tracking responses to fasting, protein intake, and smoking. This calibration-free platform establishes a powerful and versatile tool for online breath analysis, with broad potential in clinical diagnostics and exposure monitoring.