Distributed Fiber-Optic Biosensor with BRI Self-Compensation Based on a Step-Tapered Fiber and OFDR for ESCC Dual-Biomarker Detection

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies of the digestive tract, making early detection critically important for improving patient survival and treatment outcomes. Biomarker detection is routinely employed as one of the primary modalities for the identification of ESCC. Despite advantages of high sensitivity and fast response, current optical fiber biosensors still face the main challenges of multi-biomarker detection to reduce false-positive results and compensation of the interference from bulk refractive index (BRI) variations for reliable measurement. Here, we report a distributed fiber-optic biosensor capable of simultaneously detecting ESCC dual biomarkers with BRI self-compensation. A step-tapered fiber (STF) sensor is designed with two distinct tapered regions for biomarker detection with BRI compensation. Optical frequency domain reflectometry is employed to simultaneously interrogate the two regions, enabling accurate and rapid detection of ESCC dual biomarkers in a single-shot distributed measurement. Simultaneous detection of both Cyfra21-1 and squamous cell carcinoma antigen (SCCA) biomarkers has been demonstrated within a short assay time of less than 30 min and with an average relative error of 13.8 and 15%, respectively, showing 4.5 times and 11.5 times accuracy improvement when compared to those without BRI compensation. Limits of detection of 0.07 and 0.1 ng/mL have been achieved for Cyfra21-1 and SCCA detection, respectively. The capability of multi-biomarker detection with BRI self-compensation would greatly reduce false-positive rates in ESCC diagnosis.