A THz/SERS Dual-Mode Immunoassay Based on Gold Nanoparticle-Coupled Metasurfaces for Sensitive Detection of Tumor Markers

In this study, a dual-mode immunoassay that combines terahertz (THz) and surface-enhanced Raman scattering (SERS) techniques was proposed for the detection of tumor markers (TMs). The biosensor employs a polarization-independent metamaterial (MM) composed of a planar array of cross-shaped four-split resonant rings as the THz resonator and SERS substrate. The capture antibody (Ab2) immobilized on the metasurface enables the specific recognition of the target TM. Simultaneously, gold nanoparticles (AuNPs) are conjugated with a label antibody (Ab1) and attached to the Raman reporter molecule 6-carboxy-X-rhodamine (6-ROX) to fabricate a double-signal nanoprobe (AuNPs-Ab1@ROX). In the presence of the target, the nanoprobe binds to form sandwich-type immune complexes on the metasurface via antigen–antibody interactions. THz detection was performed via transmission THz time-domain spectroscopy (THz-TDS), and SERS signals were collected with a 633 nm excitation laser. The constructed dual-mode method exhibited excellent selectivity and sensitivity for the detection of the three TMs, and the limits of detection (LODs) in the THz and SERS modes were as follows: CA199 ( 0.28, and 0.26 U/mL), CA242 (0.49 and 0.13 U/mL), and POSTN (0.25 and 0.48 ng/mL). Additionally, the dual-mode immunoassay demonstrated effectiveness in quantifying CA199, CA242, and POSTN in spiked serum samples with favorable recovery. These results confirm that the dual-mode immunoassay we propose can detect multiple TMs with high sensitivity and thus holds promising application prospects in the combined analysis of TMs and early cancer diagnosis.