Highly sensitive Love-wave surface acoustic wave immunosensor for point-of-care detection of Cyfra21-1 in saliva

Decentralized biomarker testing is pivotal for cancer screening, risk evaluation, and longitudinal surveillance, yet most established assays remain laboratory-centric that are not suitable for point-of-care testing (POCT). Saliva has attracted extensive attentions owing to its redundant bioinformation, non-invasive collection and easy sampling for disease screening. Herein, we developed a highly sensitive Love-wave surface acoustic wave (Love-SAW) immunosensor for the quantification of Cyfra21-1 in saliva, a clinically established cytokeratin-19 fragment widely used in epithelial cancer management, and advanced it toward a chip-scale sensing platform that can be readily integrated into portable POCT devices. The immunosensor employs a sandwich immunoassay, with signal amplification by gold nanoparticle–labeled antibodies. The sensing interface is engineered via cysteamine self-assembly on gold through Au–S coupling, followed by glutaraldehyde activation to enable covalent immobilization of the Cyfra21-1 coating antibody. Cyfra21-1 was measured in both PBS and artificial saliva samples, with a total assay time of approximately 20 min per sample. The Love-SAW immunosensor provided a dynamic detection range of 7.81–62.5 ng/mL and a limit of detection of 4.9 ng/mL for Cyfra21-1 detection in PBS, and demonstrated matrix-tolerant detection in spiked artificial saliva (15.62–125 ng/mL, LOD: 13.9 ng/mL). Quantification in spiked artificial saliva agreed well with ELISA, yielding good recoveries of 82.36%–106.60%. These results demonstrate that the gold-enhanced Love-SAW immunosensor enables highly sensitive, rapid and portable quantification of salivary biomarkers, providing a promising foundation for the development of compact and non-invasive POCT systems for disease screening.