Optical biosensors are frontrunners for the rapid and real-time detection of analytes, particularly for low concentrations. Among them, whispering gallery mode (WGM) resonators have recently attracted a growing focus due to their robust optomechanical features and high sensitivity, measuring down to single binding events in small volumes. In this review, we provide a broad overview of WGM sensors along with critical advice and additional “tips and tricks” to make them more accessible to both biochemical and optical communities. Their structures, fabrication methods, materials, and surface functionalization chemistries are discussed. We propose this reflection under a pedagogical approach to describe and explain these biochemical sensors with a particular focus on the most recent achievements in the field. In addition to highlighting the advantages of WGM sensors, we also discuss and suggest strategies to overcome their current limitations, leaving room for further development as practical tools in various applications. We aim to provide new insights and combine different knowledge and perspectives to advance the development of the next generation of WGM biosensors. With their unique advantages and compatibility with different sensing modalities, these biosensors have the potential to become major game changers for biomedical and environmental monitoring, among many other relevant target applications.
A pH sensor can help understand chemical conditions of solutions, such as precise cell culture medium monitoring in real time. High-quality whispering-gallery-mode (WGM) microresonators have been utilized for surface sensing and are mainly based on the tracking of refractive index changes occurring within a wavelength range from their wall surface. This high sensitivity, reaching up to 10-5 RIU (~2.5 nm/RIU and measured at a femtometer resolution) leads to a broad range of applications, especially for biosensing purposes through the monitoring of molecular binding events. Here, we study the deposition of thin layers of poly(vinyl alcohol)/poly(acrylic acid) (PVA/PAA) hydrogels inside a whispering gallery mode (WGM) microbubble resonator (MBR), fabricated inline with a silica capillary. The generation of such layers is achieved by withdrawing a liquid solution of 25% PVA/PAA in pure water into the MBR and locally heating the microbubble region, resulting in hydrogel formation only in the cavity. The capillary is then rinsed and tested with varying pH solutions. The swelling ability of these gels is directly proportional to the pH of samples brought into contact with the cavity, leading to physical modifications of the WGM coupling properties. We show the preliminary results obtained for the polymerization and characterization of these gels in microbubbles and present the related signal shifts observed for several pH values. We also discuss the gel kinetics over time and investigate practical uses such as reversible and tunable detection of small pH changes.
Whispering Gallery Mode (WGM) microresonators are a class of optical sensors with the ability to trap and confine light under optical resonance conditions. Typically, this resonance is excited inside a WGM resonator using expensive and bulky tunable diode lasers, which can be a limiting factor in low-resource settings and in developing economies. In the manuscript, we describe a method of “reverse tuning” to modify the resonance conditions, paving the way for lower cost WGM excitation and ultimately lower cost sensing. We demonstrate three different methods of reverse tuning the WGM using temperature, pressure, and refractive index in a microbubble resonator (MBR), a subclass of WGM sensors that is particularly well-suited for reverse tuning using the three aforementioned methods. By reducing the cost of the MBR platform through reverse tuning, we can make these ultra-sensitive devices more practical and accessible in low-resource settings.
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