Lateral flow immunoassay (LFIA) has emerged as an effective technique in the field of food safety and environmental monitoring. However, sensitive and quantitative detection is still challenging for LFIAs in complex environments. In this work, a dual-model colorimetric/SERS lateral flow immunoassay for ultrasensitive determination of clenbuterol was constructed based on a metallic core–shell Au/Au nanostar acting as a multifunction tag. Raman reporter molecules are located between the core (AuNP) and shell (Au nanostar) to form a sandwich structure, which contributes to eliminate the environmental interference and improve the detection stability. In addition, the Au/Au nanostar provides a much higher Raman enhancement due to the presence of sharp tips and larger surface roughness in comparison with gold nanoparticles (AuNPs). Thus, on the basis of the antibody–antigen interaction, the dual-model immunoassay can produce strong colorimetric and surface-enhanced Raman spectroscopy (SERS) signals for highly sensitive detection of the target analyte, clenbuterol. Under optimal conditions, clenbuterol could be detected by the colorimetric model with a visual detection limit of 5 ng/mL. Meanwhile, the SERS signal of the Au/Au nanostar was accumulated on the test line for the SERS model detection with a quantitative detection limit as low as 0.05 ng/mL, which is at least 200-fold lower than that of the traditional AuNPs-based immunoassay. Furthermore, recovery rates of the proposed method in food samples were 86–110%. This dual-model immunoassay provides an effective tool for antibiotic residues analysis and demonstrates a broad potential for future applications in food safety monitoring.

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