Synthesis of raspberry-like nanogapped Fe₃O₄@Au nanocomposites for SERS-based lateral flow detection of multiple tumor biomarkers

Accurate detection of multiple tumor biomarkers in clinical samples is critical for the early detection and treatment of cancers. Herein, we proposed a novel surface-enhanced Raman scattering (SERS)-based lateral flow immunoassay (LFIA) for the ultra-sensitive and simultaneous quantification of multiple tumor biomarkers by using raspberry-like Fe3O4@Au magnetic nanoparticles (RAuMNPs) as multifunctional SERS tags. Nanogapped RAuMNPs with abundant interior hot spots, superior magnetic properties, and good dispersity were first synthesized via an improved seed growth method. After being modified with Raman report molecules and specific antibodies, the RAuMNPs were used as separation tools for the magnetic enrichment of target tumor biomarkers in serum and as nanogapped SERS tags for the quantitative detection of targets on LFIA strips. Using this strategy, multiplexed analysis of three common tumor biomarkers was conducted in one LFIA strip, resulting in limits of detection of 1.43 pg mL-1 for prostate specific antigen, 1.92 pg mL-1 for alpha-fetoprotein, and 3.84 pg mL-1 for carcinoembryonic antigen. The clinical feasibility of the proposed assay was also evaluated by measuring the three biomarker levels in clinical serum samples of deidentified cancer patients. The proposed assay is a promising multiplex diagnostic platform for the accurate detection of tumor biomarkers.