A Au/Cu-COF Membrane-Based SERS Sensor for Noninvasive Detection of Helicobacter pylori via Exhaled Breath Ammonia

A surface-enhanced Raman scattering (SERS) sensor built on a free-standing Au/Cu-covalent organic framework (COF) membrane was developed for the noninvasive Helicobacter pylori detection by quantifying trace ammonia in exhaled breath. The porphyrin-based Cu-COF acts as a multifunctional sensing interface, using its porous structure and accessible porphyrin-Cu coordination sites to efficiently capture and preconcentrate ammonia vapor. The change of intensity of the characteristic SERS peak at the 391 cm–1 Raman peak (ΔI391) shows a good linear relationship with ammonia concentration in the range of 0.5 to 3 ppm, with a limit of detection (LOD) down to 0.5 ppm. The sensor shows good stability and anti-interference ability toward common volatile organic compounds (VOCs) and inorganic gases in breath, allowing rapid detection without complex sample pretreatment. Notably, the introduction of Cu2+ significantly enhanced the crystallinity and structure ordering of the COF membrane, offering a new strategy for metal-ion-mediated structural regulation of 2D COF films. Preliminary clinical blind testing on exhaled breath samples yields a 70% diagnostic accuracy for H. pylori infection, validating the practical potential of this sensor. This work establishes a robust SERS platform for breath biomarker analysis and provides a promising route for noninvasive, real-time, and point-of-care diagnosis of H. pylori infection.