Optimized SARS-CoV-2 spike protein detection via coupling coefficient-driven fast fourier transform analysis in a peptide-functionalized fiber optic biosensor

In this work, we present a novel fiber optic-based biosensor designed for the detection of the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein. The sensor leverages the precise control of light within a Fabry-Pérot cavity, where the external wall is chemically functionalized with two peptides derived from the ACE2 protein that exhibit a high affinity for the spike protein. Our approach is centered on monitoring variations in the coupling coefficient, which directly affects the power of the reflected light beam coupled back into the fiber core. These variations are detected by analyzing the interference patterns of the reflected light using Fourier Transform techniques. The sensitivity of the sensor is demonstrated through its ability to detect minute changes in the coupling coefficient as the concentration of the spike protein increases, with detection limits as low as 0.018 ng/mL when all peptides are used together. The sensor exhibits exceptional sensitivity, selectivity, and repeatability, with a strong linear correlation (R² = 0.99) between the FFT intensity and the protein concentration. This innovative biosensor design offers significant advantages, including real-time analysis, high sensitivity, and the potential for miniaturization, making it a promising tool for the rapid and accurate detection of SARS-CoV-2 and other viral pathogens containing the RBD region. Moreover, although our approach has been experimentally evaluated for the spike protein, the biosensor could be readily adapted for the detection of other pathogens by redesigning the functionalized peptides to target new biomarkers, thereby providing a versatile platform for addressing current and future challenges in viral detection.