Tunable Morphology of Au Nanostars Enhances Dual-Modal Lateral Flow Immunoassay for Sensitive SARS-CoV-2 Antibody Detection

Abstract

While various labels have been developed for dual-modal colorimetric and photothermal detection, gold-based nanostructures remain highly attractive due to their ease of surface functionalization and biocompatibility. Here, we present a class of gold nanostars (Au NSs) with precisely engineered branched morphologies that offer not only straightforward synthesis and efficient modification but also significantly enhanced photothermal performance. Integrated into a lateral flow immunoassay (LFIA) platform for detecting SARS-CoV-2 nucleocapsid (N) protein antibodies, these Au NSs enable both visual qualitative interpretation and quantitative photothermal readout. A human-derived monoclonal antibody (clone CH-14) targeting the N protein was used as the standard for calibration, ensuring structural and functional consistency with natural antibodies in clinical samples. Under optimized conditions, the assay achieves detection limits of 10⁴ pg/mL (colorimetric) and 107 pg/mL (photothermal), and demonstrates high specificity, reproducibility, and successful validation with clinical human serum samples. This work establishes a sensitive, reliable, and industrially scalable LFIA strategy for point-of-care serological testing.