Wavefront-modulated Fabry–Perot fiber biosensor for label-free lysozyme detection via coupling efficiency analysis

We report an antibody-mediated biorecognition strategy for the label-free detection of lysozyme using a fiber-based Fabry–Perot biosensor that leverages wavefront perturbation as its core transduction mechanism. Unlike conventional refractometric sensors, our approach detects wavefront-induced variations in the modal coupling efficiency ( η ), which are highly sensitive to subtle geometric deformations of the reflected beam at the sensing interface. The biosensor integrates a microcavity at the tip of a single-mode fiber, covalently functionalized with anti-lysozyme antibodies. Upon antigen binding, the reflected wavefront is distorted, decreasing the overlap with the guided mode and thereby reducing η , which leads to measurable changes in the reflected spectrum. Fast Fourier Transform (FFT) analysis of the interference pattern enables highly sensitive, real-time quantification of lysozyme, achieving a limit of detection (LOD) of 0.782 ng/mL and a linear response from 50 to 1000 ppb, to the best of our knowledge the lowest LOD reported for fiber-based Fabry–Perot lysozyme biosensors. The modular design allows for antibody substitution without compromising optical performance, making the sensor adaptable to other targets. This work demonstrates a scalable, miniaturizable platform for selective biosensing based on wavefront modulation rather than bulk refractive index shifts, opening new possibilities in clinical, environmental, and industrial diagnostics. • Antibody-functionalized Fabry–Perot fiber-optic biosensor for lysozyme detection. • Coupling coefficient modulation used as the sensing principle. • Perturbation-induced wavefront deformation analyzed via FFT spectral processing. • Detection limit of 0.782 ppb in complex biological media and 0.789 ppb in buffer. • Label-free, rapid, and highly reproducible sensing platform for real-world applications.