Magnetic core–satellite SERS biosensor for ultrasensitive quantification of squamous cell carcinoma antigen in human serum

Squamous cell carcinoma antigen (SCCA) a magnetic enrichment–assisted core–satellite surface-enhanced Raman scattering (SERS) biosensor for ultrasensitive squamous cell carcinoma antigen (SCCA) detection is reported. Magnetic nanoparticles functionalized with SCCA capture antibodies act as enrichment cores, while 4-mercaptobenzoic acid (MBA)–encoded Au@Ag core–shell nanoparticles conjugated with SCCA detection antibodies serve as SERS satellites. Target-mediated sandwich immunorecognition induces a dynamically assembled core–satellite structure, bringing plasmonic nanogaps into close proximity and generating reproducible electromagnetic hot spots for signal amplification. Magnetic pre-enrichment and controlled assembly help reduce nonspecific protein interference in serum and contribute to stable signal generation. The biosensor exhibited a monotonic concentration-dependent Raman response over the range of 1 fg/mL to 10¹¹ fg/mL and achieved a limit of detection (LOD) of 60.0 fg/mL. Quantitative determination of serum samples was performed using an independently established matrix-matched calibration curve. The platform was further validated using real human serum samples from early-stage lung SqCC patients ( n  = 8) and healthy controls ( n  = 8), showing higher SCCA concentrations in patient samples than in healthy controls and clear discrimination between the two groups. Overall, the proposed magnetic enrichment–assisted core–satellite SERS immunoassay provides a robust analytical strategy for sensitive SCCA quantification in complex serum matrices. Graphical abstract