Electrochemical Label-Free Detection of Biomarkers towards Phenotyping of Airway Inflammation

: The management of airway disease based on phenotypic characteristics is limited by the absence of diagnostic tools capable of concurrently addressing multiple inflammatory pathways. Traditional assessments provide isolated measurements, which fail to capture intricate interactions among early immune activation, systemic dissemination, neutrophil recruitment, and viral immune response. These are four critical mechanisms that influence disease progression and therapeutic outcomes. In this study, we introduce a non-faradaic electrochemical impedance spectroscopy biosensor designed for a label-free parallel measurement of C-reactive protein (CRP), IP-10 (CXCL10), interleukin-6 (IL-6), and interleukin-8 (IL-8). The platform uses frequency-specific impedance analysis to detect binding events in capacitance at the electrode-electrolyte interface, allowing for direct concentration-dependent detection. It offers wide dynamic ranges covering both physiological and pathological concentrations for all four analytes. Analytical validation showed a strong correlation between spiked and recovered concentrations (R 2 > 0.95), with percent recovery within the 80-120% accuracy range and cross-reactivity below 20% under multiplexed conditions, confirming the platform's selectivity and quantitative reliability. Both intra- and inter-assay reproducibility met analytical standards. By incorporating four distinct inflammatory biomarkers into a single impedance framework, this platform moves airway diagnostics beyond isolated measurements to a multi-dimensional phenotype resolution, laying the groundwork for decentralized risk assessment and therapy-guided inflammatory monitoring.