From Whispering Gallery Mode Resonators to Biochemical Sensors

Abstract

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.

Advancements and Perspectives in Optical Biosensors

“…The optical resonance condition , for WGM is denoted as m λ = 2π Rn eff for one round trip, where the integer number is denoted as m , λ is the light wavelength, R is the radius of the resonator, and n eff is the effective refractive index between the resonator and the environment. Hence, any change in the physical size or the refractive index of the resonator induced by a variation of bioassays or chemical composition of the medium would change the resonance condition in a way such as wavelength shifting, mode splitting, and the line width broadening of the initial condition.…”

Microsphere-Enabled Micropillar Array for Whispering Gallery Mode Virus Detection

“…Whispering gallery mode (WGM) resonator-based sensing is one of the most sensitive optical sensing techniques . WGMs are generated by light being confined at the circular interface of the resonator by means of total internal reflection.…”

Optimization of Surface Functionalizations for Ring Resonator-Based Biosensors

“…Regarding recognition elements, several molecules have been proposed, such as peptides [21], aptamers [22,23], or molecular-imprinted polymers (MIPs) [24]. The most exploited class, however, is that of antibodies [22,25] or antibody fragments [19], thanks to their sensitivity and selectivity properties; however, aptamers are also emerging as convenient recognition elements. Aptamers are single-stranded nucleotide chains that specifically bind target molecules with high affinity and selectivity via secondary-structure formation.…”

“…They have several advantages with respect to antibodies, including the fact that they work under more severe conditions, i.e., in environments different from physiological systems, as they are less sensitive to variations in pH, hydration, and temperature, which allows them to survive under harsh regeneration steps. Moreover, aptamers show reduced batch-to-batch variation compared to antibodies and can be modified by adding selective chemical groups and spacers at predetermined positions, allowing for substrate-oriented immobilization and limiting steric hindrance for an optimized binding [22,23]. The covalent binding of aptamers to the silanized surface was selected in this work as the most promising functionalization strategy for MRR biosensors.…”