Nanoplasmonic core–shell nanoraspberry chip for ultrasensitive surface-enhanced Raman scattering detection of SARS-CoV-2: a modular nanobiosensor for respiratory virus diagnostics

Abstract

The development of robust and ultrasensitive point-of-care diagnostics for viral pathogens, particularly for seasonal respiratory viruses, remains a critical challenge, as traditional biosensing platforms often suffer from signal instability and poor performance in complex biological matrices. Here, we report a dual-component surface-enhanced Raman scattering (SERS) immunosensor designed to mitigate some of these limitations through a new hotspot engineering strategy. Our platform is centred on a core–shell Au@Ag nanotag fabricated from branched gold nanoraspberries (AuNRBs), which provides a high density of plasmonic hotspots. A conformal Ag shell confines the 4-aminothiophenol (4-ATP) reporter within these nanogaps, establishing a unique “gap-confined” Raman reporter architecture that enhances signal stability and reproducibility. This nanotag is complemented by a second SERS-active component: a capture sensor chip of fluorine-doped tin oxide (FTO) modified with a dense layer of Au nanoparticles (AuNPs). When implemented in a sandwich immunoassay for the SARS-CoV-2 S2 spike protein, this dual-enhancement platform achieved a sensitive detection range of 1–500 ng mL⁻¹ with an ultralow limit of detection of 1.07 pg mL⁻¹ (15.3 fM) in PBS and 1.30 pg mL⁻¹ (18.6 fM) in human serum albumin (HSA). Although these results demonstrate strong analytical sensitivity and rapid assay performance within 30 min, further studies are required to assess clinical robustness, scalability and long-term stability. Overall, this work demonstrates the potential of the proposed SERS system as a versatile platform for rapid, on-site pathogen diagnostics.