Dual-Format Plasmonic Biosensors for the Detection of SARS-CoV-2 and the Oxidative Stress Biomarker sNOX2-dp

Abstract The integrated surveillance, combining wastewater-based epidemiology (WBE) with clinical biomarker detection, is a game-changer approach to give a big-picture view of human health in large areas. In the present study, we introduce and evaluate 2 plasmonic biosensing architectures specifically designed for detecting two analytical targets relevant for integrated surveillance: the SARS-CoV-2 Spike protein and the sNOX2-derived peptide (sNOX2-dp). The former is an analytical target for SARS-CoV-2 virus in different matrices; the latter is a biomarker of oxidative stress. It is one of the physiological responses to SARS-CoV-2 infection, crucial for SARS-CoV-2-positive individuals with severe symptoms or thrombotic complications. The two distinct biosensing architectures are plasmonic optical transducers based on gold nanorods (AuNRs), functionalized with monoclonal antibodies. They are designed to recognize and quantify SARS-CoV-2 Spike protein or sNOX2-dp from the shift of AuNR longitudinal plasmon band wavelength. For both the analytical targets, we realize and characterize AuNR-based optical probes in two distinct configurations: on a solid support (AuNR arrays) and as colloidal dispersion (AuNR bioconjugates). After screening AuNR array and bioconjugate-based sensors as a function of morphology and preparation conditions, we assess their quantitative detection performance for the respective targets. Array-based sensors exhibited lower limits of blank compared to their colloidal counterparts, both toward the SARS-CoV-2 Spike protein (0.39 ng mL−1) and toward sNOX2-dp (0.96 μg mL−1), however bioconjugates exhibited specificity and fast response time. A head-to-head comparison highlights AuNR arrays as optimal for high sensitivity and cost-efficient environmental and clinical monitoring, whereas AuNR bioconjugates enable faster and specific analytical response suitable for point-of-care applications. Overall, this adaptable plasmonic platform bridges WBE and clinical diagnostics, enabling scalable infectious disease surveillance and prevention across a wide concentration range.