Dual-Mode Immunoassay with Au@Cu Core–Shell Nanotags: Kinetic-Driven Signal Amplification for Ultrasensitive On-Site Detection of Biomarkers

Metal nanoparticle-labeled immunoassays hold great promise for point-of-care biomarker detection, but there are few integrated platforms that simultaneously achieve ultrahigh sensitivity, true portability, and high reliability, which are essential for credible on-site diagnostics. Herein, we report a self-validated dual-mode immunoassay platform with Au@Cu-labeled nanotags for biomarker detection. The kinetically controlled, self-limiting growth of Cu shells on AuNPs results in a nonlinear copper deposition that greatly amplifies the immunoassay signal. By integrating this amplification strategy with miniaturized capillary liquid electrode glow discharge-optical emission spectrometry (CLEGD-OES), we developed a dual-mode immunoassay platform that combines the rapid, visual screening capability of colorimetry with the high sensitivity of atomic emission spectrometry, effectively realizing field-deployable rapid testing and laboratory-grade quantitative analysis. This portable device was applied for on-site detection of three major biomarkers: carcinoembryonic antigen (CEA), cardiac troponin I (cTnI), and amyloid-β (Aβ), achieving limits of detection of 2.0 × 10 4 fg mL –1, 3.5 fg mL –1, and 10.3 × 10 3 fg mL –1, respectively. The successful integration of kinetic amplification with a dual-mode readout offers a novel, powerful, and reliable tool for early disease screening in resource-limited settings.