Cascaded Plasmonic Coupling Based on Tilted Fiber Bragg Grating Sensors for Ultrasensitive and Noninvasive microRNA Detection

MicroRNAs (miRNAs) serve as critical biomarkers for cancer diagnosis and disease monitoring due to their dysregulated expression in malignancies. However, their low abundance, short length, and high sequence similarity pose significant detection challenges. Here, we present a plasmonic sensing platform that integrates Au@ZIF-8 core-shell nanostructures with a gold-coated tilted fiber Bragg grating surface plasmon resonance sensor. This hybrid architecture enhances plasmonic coupling by generating a three-dimensional localized electromagnetic field. The spatially extended sensing region improves responsiveness to large-scale biomolecular targets. Target recognition utilizes a sandwich probe design combining immobilized ssDNA capture strands with ssDNA-functionalized gold nanoparticles (AuNPs) as signal amplifiers. AuNPs convert minute refractive index (RI) variations induced after miRNA binding into amplified RI perturbations, with the transduction process precisely confined to the cascaded plasmonic coupling sites between the AuNPs and Au@ZIF-8 nanostructures. This selective signal enhancement mechanism improves sensitivity and suppresses nonspecific background signals. We further demonstrate multiplexed detection of two breast cancer-related miRNAs within 30 min, effectively doubling throughput relative to single-target assays. The platform achieves detection limits as low as 5.94 aM (pure water), 13.6 aM (serum), and 7.78 aM (saliva), with recovery rates exceeding 94% in complex biofluids. This ultrasensitive, high-throughput, and noninvasive sensor holds promise for early cancer screening, disease staging, and therapeutic evaluation.