Nucleic-Acid-Amplification-Free and Fluorescent-Label-Free RNA Detection with a Dual-Scale Gold Nanoparticle−Enhanced Fiber-Optic SPR Biosensor

in: Analytical Chemistry (2026)
Li, Xuegang; Zhao, Xingyu; Zhang, Jing; Zhang, Yanan; Zhao, Yong; Warren-Smith, Stephen C.; Nguyen, Linh Viet; Zhou, Xue
Highly sensitive RNA detection at ultralow concentrations remains challenging for conventional surface plasmon resonance (SPR) biosensors because low-molecularI biomolecules induce only weak effective refractive-index perturbations within the limited evanescent-field penetration depth. Here, we report a dual-scale gold nanoparticle (AuNP)−enhanced fiber-optic SPR biosensor that overcomes this intrinsic limitation through a mechanism-guided sandwich-type architecture. The sensor employs a multimode fiber−single-mode fiber−multimode fiber (MMF−SMF−MMF) configuration to enhance evanescent-field excitation at the metal−dielectric interface. Plasmonic amplification is achieved by decoupling probe immobilization and signal enhancement into two AuNP populations with distinct roles: large AuNPs functionalized with probe DNA form a stable, high-density recognition layer on the gold-coated fiber surface, while small AuNPs conjugated with target RNA act as mobile amplification units. Upon specific DNA−RNA hybridization, a hierarchical plasmonic sandwich structure is formed within the effective sensing volume, enabling synergistic enhancement through near-field electromagnetic coupling and mass-loading effects. Finite-element simulations and experiments consistently demonstrate substantially stronger localized electromagnetic fields and higher refractive-index sensitivity compared with bare gold films and monolayer AuNP-modified SPR sensors. Importantly, the assay does not rely on nucleic-acid amplification reactions or fluorescent labeling. The sensor exhibits a linear response to RNA concentrations from 0 to 700 fM, achieving a sensitivity of 6.5 pm/fM and a detection limit of 97 fM, corresponding to a 7.5-fold signal enhancement over conventional single-layer AuNP-based SPR sensors. This work demonstrates that a dual-scale AuNP assisted sandwich architecture can effectively amplify weak SPR responses from thiol-modified model RNA targets without requiring nucleic-acid amplification reactions. Further optimization toward direct detection of unmodified RNA in real biological samples will be pursued in future work.

Cookies & Skripte von Drittanbietern

Diese Website verwendet Cookies. Für eine optimale Performance, eine reibungslose Verwendung sozialer Medien und aus Werbezwecken empfiehlt es sich, der Verwendung von Cookies & Skripten durch Drittanbieter zuzustimmen. Dafür werden möglicherweise Informationen zu Ihrer Verwendung der Website von Drittanbietern für soziale Medien, Werbung und Analysen weitergegeben.
Weitere Informationen finden Sie unter Datenschutz und im Impressum.
Welchen Cookies & Skripten und der damit verbundenen Verarbeitung Ihrer persönlichen Daten stimmen Sie zu?

Sie können Ihre Einstellungen jederzeit unter Datenschutz ändern.