Whispering Gallery Mode Resonators for Rapid Label-Free Biosensing in Small Volume Droplets

Abstract

Rapid biosensing requires fast mass transport of the analyte to the surface of the sensing element. To optimize analysis times, both mass transport in solution and the geometry and size of the sensing element need to be considered. Small dielectric spheres, tens of microns in diameter, can act as label-free biosensors using whispering gallery mode (WGM) resonances. WGM resonances are sensitive to the effective refractive index, which changes upon analyte binding to recognition sites on functionalized resonators. The spherical geometry and tens of microns diameter of these resonators provides an efficient target for sensing while their compact size enables detection in limited volumes. Here, we explore conditions leading to rapid analyte detection using WGM resonators as label-free sensors in 10 μL sample droplets. Droplet evaporation leads to potentially useful convective mixing, but also limits the time over which analysis can be completed. We show that active droplet mixing combined with initial binding rate measurements is required for accurate nanomolar protein quantification within the first minute following injection.

Applications of Optical Microcavity Resonators in Analytical Chemistry

“…For example, microspheres resting on a surface can be interrogated via a prims (32, 64, 65). Additionally, the use of fluorescent microparticles as the microcavity itself eliminates the need for optical waveguides or fiber-optics altogether, as the fluorescence generated by a focused laser spot can be confined within the microcavity (66–68).…”

Label-Free Biological and Chemical Sensing Using Whispering Gallery Mode Optical Resonators: Past, Present, and Future

“…These resonators behave as both the resonator and the sample. In these resonators, evaporation can speed up reactions, enabling lower limits of detection, but limiting experiment times [65]. Diamond resonators are also potentially attractive biosensors.…”

Recent advances in microscale western blotting

“…77–80 These approaches are generally rapid, quantitative, require minimal antibody, and are easily multiplexed; thus offering intriguing metrics worth exploring. 81,82 …”

“…WGM sensing is compatible with both capillary and microchip based separations, each resonator (assay) requires trace amounts of antibody, and quantitative assays can be completed in minutes, significantly improving analysis times. 81,91,92 However, much work is needed to explore the practical limits of such an approach. Biosensing performance is strongly dependent on analyte transport to the sensing surface, which depends on a number of factors.…”

“…In such applications, the potential for real-time, multiplexed detection of proteins following a separation step offers exciting opportunities. 81,88,97 …”