Optical whispering gallery mode (WGM) biochemical sensors operate by tracking changes in resonant frequency as materials enter the evanescent near-field of the resonator. To achieve the smallest limit of detection, it is desirable for WGM sensors to exhibit as large a frequency shift as possible for a material of a given size and refractive index, as well as the ability to track as small a frequency shift as possible. Previously, plasmonic nanoantennas have been coupled to WGM resonators to increase the magnitude of resonance shifts via plasmonic enhancement of the electric field, however this approach also results in increased scattering from the WGM, which degrades its quality factor, making it less sensitive to extremely small frequency shifts. This degradation is caused by the ohmic and scattering dissipation caused by metallic nanoantennas. Using simulations, we show here that the precise positioning of nanoantennas coupled to a microtoroid WGM resonator can be used to overcome this drawback and achieve ultrahigh-Q plasmonic cavity modes simultaneously with electric field enhancement. It is shown that a nanoantenna composed of two similarly coupled nanorods supports higher Q modes than a single nanorod antenna. Our results have immediate application in the context of optical sensing.
Recently exosomes have attracted interest due to their potential as cancer biomarkers. We report the real time, label‐free sensing of single exosomes in serum using microtoroid optical resonators. We use this approach to assay the progression of tumors implanted in mice by specifically detecting low concentrations of tumor‐derived exosomes. Our approach measures the adsorption of individual exosomes onto a functionalized silica microtoroid by tracking changes in the optical resonant frequency of the microtoroid. When exosomes land on the microtoroid, they perturb its refractive index in the evanescent field and thus shift its resonance frequency. Through digital frequency locking, we are able to rapidly track these shifts with accuracies of better than 10 attometers (one part in 10^11). Samples taken from tumor‐implanted mice from later weeks generated larger frequency shifts than those from earlier weeks. Control samples taken from a mouse with no tumor generated no such increase in signal between subsequent weeks. Analysis of shifts from tumor-implanted mouse samples show a distribution of unitary steps, with the maximum step having a height of ~1.2 fm, corresponding to an exosome size of 44 ± 4.8 nm. This size range corresponds to that found by performing nanoparticle tracking analysis on the same samples. Our results demonstrate development towards a minimally‐invasive tumor "biopsy" that eliminates the need to find and access a tumor.