Graphene-like oxide-supported plasmonic nanostructures combined with initial reaction analysis for label-free detection of tumor biomarkers

Abstract

The advancement of nanoplasmonics and meta-optics has positioned localized surface plasmon resonance (LSPR) biosensing as an attractive technology for point-of-care testing (POCT), overcoming key limitations of traditional propagating surface plasmon resonance (PSPR) in terms of miniaturization and cost. However, the multistep and complex surface chemistry required for conventional nanostructure-based LSPR biosensors remains a major obstacle to their reproducible and efficient fabrication. To address this issue, we developed a more streamlined surface modification strategy based on magnetron sputtering of a uniform graphene-like carbon (GLC) nanofilm onto ultrasmooth gold nanogroove arrays (UGNA), followed by electrochemical oxidation to enable direct biomolecular coupling. This graphene-like oxide-modified UGNA (GO-UGNA) eliminates the need for intermediate linking layers, significantly simplifying the fabrication process while maintaining efficient probe immobilization. Utilizing a miscellaneous-protein strategy combined with initial rate analysis, the biosensor detected tumor markers carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3), and carbohydrate antigen 72-4 (CA72-4), achieving broad linear ranges (1–1000 U/mL) in both wavelength-based and intensity-based detection modes. The limits of detection were 0.410 U/mL, 0.486 U/mL, and 0.690 U/mL for CA19-9, CA15-3, and CA72-4 in wavelength mode, whereas those in intensity mode were 0.119 U/mL, 0.103 U/mL, and 0.458 U/mL, respectively. Clinical sample analysis demonstrated excellent concordance with a commercial electrochemiluminescence system (Roche Cobas 8000 e801). With its rapid modification process (∼10 min) and reproducible fabrication, this work establishes a promising platform for developing practical, low-cost POCT biosensors with clinical-grade accuracy. © 2026 Elsevier B.V.