Nanoplasmonic optical fiber sensing of SARS-CoV-2 nucleocapsid protein using an aptamer-DNA tetrahedron interface

Abstract Optical fiber sensing carries a number of potential advantages for diagnostics and biomarker detection and monitoring, yet particular challenges persist in linking molecular recognition events to a change in the refractive index. DNA aptamers carry particular advantages as functional surface molecules on optical fibers to tailor detection of specific biomolecules, yet challenges persist around sensitivity and specificity. Diagnosis of COVID-19 through detection of nucleocapsid protein (N protein) of SARS-CoV-2 provides a classic diagnostic challenge where optical fiber-based sensing could complement and improve on typical detection methods such as RT-PCR and rapid antigen testing. In this study, a plasmonic gold-coated tilted fiber Bragg grating (TFBG)-based optical biosensing platform was developed for ultrasensitive detection of SARS-CoV-2 N protein. By functionalizing the optical fiber surface with aptamers for the molecular recognition of N protein, changes in refractive index measured biomolecular binding, thereby achieving real-time, label-free detection. Additionally, integrating DNA nanostructures such as the DNA tetrahedron with aptamers significantly enhanced detection sensitivity, increasing signal intensity ~ 2.5 times compared to aptamers alone. This study provides new insights into the development of high-performance optical fiber sensing platforms which integrate DNA nanostructure interfaces to facilitate biomarker recognition and sensing.