Development of a novel label-free all-fiber optofluidic biosensor based on Fresnel reflection and its applications

A novel, compact, cost-effective, and robust label-free all-fiber optofluidic biosensor (LF-AOB) based on Fresnel reflection mechanism was built through integrating single-multi mode fiber coupler and highly sensitive micro-photodetector. The Fresnel reflection light intensity detected by the LF-AOB greatly depended on the RI change on the end-surface of the fiber probe according to experimental and simulation results. The capability of the LF-AOB for real-time in situ detection in optofluidic system were verified by measuring salt and protein solution, and the lowest limit of detection was 1.0 × 10^-6 RIU. Our proposed theory can effectively eliminate the influence of light intensity fluctuation, and one-point calibration method of sensor performance is conducive for rapid and convenient detection of targets. Label-free sensitive detection of SARS-Cov-2 Spike protein receptor-binding domain (S-RBD) and the binding kinetics assay between S-RBD and anti-S-RBD antibody were achieved using the LF-AOB. These contributed to the elegant design of all-fiber optical system with high efficiency, high resolution and sensitivity of micro-photodetector, and enhanced interaction between the light and the samples at the liquid-sensor interface because of the large surface area of the multi-mode fiber probe. The LF-AOB can be extended as a universal sensing platform to measure other factors associated with refractive index because its high sensitivity, low sample consumption (∼160 nL), and capability of real-time in situ detection.