This paper presents the meticulous design and characterization of a photonic crystal fiber (PCF)-based surface plasmon resonance (SPR) sensor, analyzed using finite element method (FEM) simulations. The sensor’s superior performance is demonstrated by its exceptional sensitivity to minute changes in the refractive index (RI) of various analytes. The optimized structure reveals a peak resonance at 0.78898 µm with a maximum confinement loss of 546.34 dB/cm. Detailed investigations show resonance wavelength red shifts of up to 0.93% with a 5% increase in air hole diameter and blue shifts of up to 0.88% with a 5% decrease. Additionally, variations in the plasmonic gold layer thickness result in resonance shifts of up to 0.76% longer or 0.87% shorter wavelengths. The sensor achieves remarkable wavelength sensitivity (WS) of up to 13,000 nm/RIU and amplitude sensitivity (AS) of up to 1538.90RIU−1, underscoring its high precision in detecting analyte concentration changes. The design’s robustness against fabrication errors, evidenced by minimal variations in resonance characteristics, highlights its practical reliability. Furthermore, the use of a polynomial regression model with an R2 value near unity accurately approximates the relationship between resonance wavelength and analyte RI, ensuring precise sensing capabilities without overfitting. Comparative analysis with existing designs confirms the sensor’s superior performance, rendering it highly suitable for a wide range of applications, including biosensing of glucose, water contaminated by cholera germs, mucosa of the human intestine, important components of human blood, and detection of chemicals like acetone, ethanol, benzene, propanol, glycerol, and expired transformer oil.
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