Hybrid Vernier Sensor Based on Fabry−Perot-Assisted Tapered Microfiber for Ultrasensitive Detection of Nucleic Acid Biomarkers

Ultrasensitive detection of nucleic acid biomarkers is vital for early disease screening and clinical diagnosis. However, conventional tapered microfiber (TMF) interferometers are constrained by limited sensitivity and detection resolution. Here, we present a Fabry-Perot-assisted tapered microfiber (FP-TMF) biosensor that implements a hybrid Vernier architecture exploiting asynchronous phase evolution. In this design, an air-cavity Fabry-Perot interferometer (FPI) serves as a static and dispersion-stable reference, with its frequency intentionally detuned from that of the highly dispersive TMF. This controlled phase mismatch generates progressively amplified Vernier envelopes, converting nanoscale refractive index (RI) perturbations into resolvable spectral shifts within a stable observation window. Using hepatitis C virus (HCV) nucleic acid biomarkers as a model, the TMF surface was functionalized with specific probes via click chemistry to enable highly selective DNA hybridization. The biosensor demonstrated about a 4-fold improvement in both RI sensitivity and detection resolution compared with a single TMF, achieving an attomolar detection limit of 0.62 aM. It further exhibited a wide dynamic range from 10^-18 to 10^-6 M, reproducible performance across independent devices, and reliable detection in serum samples. Moreover, the air-cavity reference ensures thermal robustness, allowing effective temperature compensation and reliable discrimination of binding signals from environmental variations. By integrating dispersion engineering with a stable reference, this FP-TMF Vernier biosensor provides a simple and effective approach to enhance optical biosensing resolution, offering a robust platform for ultrasensitive nucleic acid detection.