Biomimetic Tri-Phase Hierarchical Interface Enables Ultra-Efficient Enrichment and Sensing of Respiratory Viruses in Exhaled Breath.

Publication date: Aug 22, 2026

The analysis of exhaled breath condensate (EBC) for respiratory pathogen detection is fundamentally limited by the extreme dilution of target analytes, leading to insufficient sensitivity in point-of-care platforms. Here, we present a paradigm-shifting solution inspired by the efficient multi-stage capture mechanism of the human respiratory system. We engineered a tri-phasic hierarchical interface that orchestrates a synergistic cascade for viral enrichment and detection: (1) microscale pillar arrays that mimic bronchial bifurcations to direct airflow and enhance particle-surface collisions via inertial impaction; (2) a TiO2 nanowire forest that emulates the mucin network, providing a high-surface-area scaffold for analyte retention; and (3) a functionalized polymer coating for specific antibody-antigen recognition. This bio-inspired architecture, optimized through computational fluid dynamics and fabricated via wafer-level MEMS processes, achieved a 3. 6-fold increase in condensate collection and a 500% enhancement in capture-site density. When integrated into a portable fluorescence detection system, the platform demonstrated high specificity (>95%) and detected SARS-CoV-2 pseudovirus down to 3 TU/mL under the tested simulated-breath workflow. Critically, the binding kinetics, analyzed using the Hill model, further supports a saturation-like, heterogeneous capture behavior of the hierarchical interface. This work not only delivers a powerful tool for non-invasive diagnostics but also establishes a generalizable biomimetic design paradigm for next-generation biosensors targeting ultra-dilute biomarkers.