The demand for biosensor technology has grown drastically over the last few decades, mainly in disease diagnosis, drug development, and environmental health and safety. Optical resonator-based biosensors have been widely exploited to achieve highly sensitive, rapid, and label-free detection of biological analytes. The advancements in microfluidic and micro/nanofabrication technologies allow them to be miniaturized and simultaneously detect various analytes in a small sample volume. By virtue of these advantages and advancements, the optical resonator-based biosensor is considered a promising platform not only for general medical diagnostics but also for point-of-care applications. This review aims to provide an overview of recent progresses in label-free optical resonator-based biosensors published mostly over the last 5 years. We categorized them into Fabry-Perot interferometer-based and whispering gallery mode-based biosensors. The principles behind each biosensor are concisely introduced, and recent progresses in configurations, materials, test setup, and light confinement methods are described. Finally, the current challenges and future research topics of the optical resonator-based biosensor are discussed.

An optical cavity-based biosensor (OCB) has been developed for point-of-care (POC) applications. This label-free biosensor employs low-cost components and simple fabrication processes to lower the overall cost while achieving high sensitivity using a differential detection method. To experimentally demonstrate its limit of detection (LOD), we conducted biosensing experiments with streptavidin and C-reactive protein (CRP). The optical cavity structure was optimized further for better sensitivity and easier fluid control. We utilized the polymer swelling property to fine-tune the optical cavity width, which significantly improved the success rate to produce measurable samples. Four different concentrations of streptavidin were tested in triplicate, and the LOD of the OCB was determined to be 1.35 nM. The OCB also successfully detected three different concentrations of human CRP using biotinylated CRP antibody. The LOD for CRP detection was 377 pM. All measurements were done using a small sample volume of 15 µL within 30 min. By reducing the sensing area, improving the functionalization and passivation processes, and increasing the sample volume, the LOD of the OCB are estimated to be reduced further to the femto-molar range. Overall, the demonstrated capability of the OCB in the present work shows great potential to be used as a promising POC biosensor.

We have developed a low-cost optical cavity-based biosensor with a differential detection method for point-of-care medical diagnostics. To experimentally demonstrate its label-free real-time biosensing capability, we performed the detection of biotinylated bovine serum albumin (BSA). Streptavidin is introduced into the optical cavity structure and immobilized on 3-aminopropyltriethoxysilane (APTES) coated surface. After rinsing out unbound streptavidin with DI water, biotinylated BSA without any labeling is introduced. A CMOS camera captures the transmitted light of two different wavelengths passing through the optical cavity sensing area in real-time. Then, the differential values are calculated to enhance the responsivity. We successfully demonstrated the label-free real-time detection of biotinylated BSA, and the measurement results matched well with the simulation results. The limit of detection of the optical cavity-based biosensor for the biotinylated BSA detection with the sensing area of 180 μm $\times$ 180 μm is estimated to be 2.82 pM, which could be reduced further for a smaller sensing area with the tradeoff of a longer sensing time.

An optical cavity-based sensor using a differential detection method has been proposed for point-of-care diagnostics. We developed a low-cost and portable optical cavity-based sensor system using a 3D printer and off-the-shelf optical components. In this paper, we demonstrate the sensing capability of the portable system through refractive index measurements. Fabricated optical cavity samples were tested using the portable system and compared to simulation results. A referencing technique and digital low pass filtering were applied to reduce the noise of the portable system. The measurement results match the simulation results well and show the improved linearity and sensitivity by employing the differential detection method. The limit of detection achieved was 1.73 × 10⁻⁵ Refractive Index Unit (RIU), which is comparable to other methods for refractive index sensing.