Modification-free optofluidic Fabry-Pérot capillary microcavities for ultra-sensitivity biosensing

Ultrasensitive optical sensors have become an indispensable device in various fields, such as disease early intervention and personalized treatment, environmental pollution source detection, physical parameters measurement, and analysis of cellular metabolites and derivatives. In this study, we have developed an optofluidic Fabry-Pérot capillary microcavity (FPCM) sensor employing a square-capillary quartz tube for the ultra-sensitivity detection. Benefit from the highly parallel of square capillary side wall and lateral light field confinement, the deposited distributed Bragg reflector have good tolerance to the light walk of loos and diffraction, showing a fascinating quality (Q) factor of 1.0 × 10⁶. Moreover, the high overlap between the optical field and analyte molecules always indicates a high refractive index (RI) sensitivity of 201.1 nm/RIU. As a result, an ultra-high figure of merit (FOM) of 2.2 × 10⁵ RIU⁻¹ and an ultra-low detection limit of 7.11 × 10⁻⁸ RIU can be achieved with the FPCM sensors. The experimental results also demonstrated the FPCM sensor with high repeatability, exceptional long-term stability and remarkably low system noise for multiple in-situ tests with high accuracy. In biosensing applications, we initially assessed the effect of polyethylene glycol (PEG) on protein aggregation by leveraging its non-specific binding effect on goat anti-human immunoglobulin G (Anti-IgG). Both the intensity and wavelength changes can be simultaneously captured with the protein concentration changes, indicating multiparameter sensing is possible on the FPCM. Finally, a typical breast cancer monitoring protein of Human Epidermal Growth Factor Receptor 2 (HER2) was detected, showing a detection limit for HER2 protein-specific binding as low as 100 ag/mL and an extensive detection range spanning seven orders of magnitude with the PEG-enhanced approach. Notably, the FPCM biosensor exhibits cost-effectiveness, rapid response time, and the capability for ultra-sensitivity detection without labeling or modification, making it as a crucial tool for early cancer screening and disease monitoring, environmental pollution sources detection, and physical parameters measurement.