Highly Sensitive U-Shaped Fiber-Optic Surface Plasmon Resonance Biosensors Using Bi ₂ O ₂ Se and Au Nanoparticles Composite Nanomaterials for Biomedical Diagnostics

Composite nanomaterials significantly enhance sensor sensitivity in surface plasmon resonance (SPR) applications. This study presents a novel U-shaped multimode fiber–no-core fiber–multimode fiber (MMF–NCF–MMF) SPR sensor integrated with the Au film/Bi2O2Se and Au nanoparticles (AuNPs) composite system. Incorporating Bi2O2Se (an emerging 2-D semiconductor with excellent optoelectronic properties) and AuNPs, the sensor leverages plasmon mode coupling between the Au film and AuNPs, plus the synergistic electron mobility regulation of Bi2O2Se and AuNPs, to boost refractive index (RI) sensitivity. The NCF reduces transmission loss and narrows the full-width at half-maximum (FWHM), enhancing target detection performance. At an MMF–NCF–MMF length ratio of 15:4:7 mm, the composite-modified sensor achieves an RI sensitivity of 7552.31 nm/RIU—112.06% higher than the pure Au film sensor (3561.4 nm/RIU). It also exhibits a 14.3-nm FWHM reduction and a 1.24-fold figure of merit (FOM) increase (from 14.280 to 32.003), along with excellent temperature stability (RSD = 0.603%) and repeatability. For biomolecular validation, C-reactive protein (CRP)—a key clinical biomarker for inflammation and postsurgical infection—was targeted. The sensor exhibits a good concentration-dependent signal response over the range of 0.1– $25~\mu $ g/mL, with a limit of detection (LOD) optimized to 13.08 at $1~\mu $ g/mL (in accordance with the IUPAC-recommended LOD $= 3~\sigma $ /S criterion), which is consistent with the clinical ranges for moderate inflammation. By integrating SPR–localized SPR (LSPR) coupling and Bi2O2Se and AuNPs synergistic sensitization, this sensor holds substantial potential for clinical diagnosis and immunoassays.