Redox-mediated optochemical plasmonic sensing of H2O2-equivalent reducing capacity in exhaled breath condensate.

Oxidative-stress-related diseases generate elevated levels of hydrogen peroxide (H2O2) and other redox-active species in exhaled breath condensate (EBC), offering a promising avenue for non-invasive disease assessment. Despite its diagnostic potential, clinical translation of EBC redox species detection has been constrained by bulky analyzers, labor-intensive operation, and limited sensitivity. By harnessing the redox potential, we present a Redox-mediated Optochemical Plasmonic Sensing (ROPS) system, an ultrasensitive platform that enables real-time, easy-to-use, point-of-care quantitative analysis of H2O2-equivalent reducing capacity in EBC. By coupling H2O2-triggered gold nanoparticle growth on a phase-modulated plasmonic sensor, the ROPS system based on the phase-modulated interferometry achieved a detection limit of 1.19 pM and a wide dynamic range across 4 orders of magnitude. Moreover, the ROPS system demonstrated excellent reusability, maintaining stable H2O2 sensing performance over 40 reuse cycles. To enable point-of-care applications, we further developed a handheld high-efficiency EBC sampler, which harvested exhaled condensate at 2.49 μL/s and enabled an EBC-ROPS sampling-to-biosensing workflow down to 15 min. Clinical evaluation using EBC samples from lung and esophageal cancer patients and matched controls confirmed reliable quantification of trace H2O2-equivalent Au(III)-reducing capacity in complex EBC matrices, highlighting the potential of the integrated ROPS platform as a practical tool for point-of-care and non-invasive oxidative stress-related disease assessment.