Frequency Locked Microtoroid Optical Resonators as a Non-Invasive Tumor Biopsy Alternative

Abstract

Whispering gallery mode optical resonators offer an unusual coupling of rapid response time and ultra-sensitive biological and chemical detection. We have improved the signal to noise ratio of microtoroid optical resonators ∼1000-fold over standard techniques by using laser frequency locking and have applied this to assay tumor progression in mice by sensing the low concentrations of exosomes, shed by tumor cells, in serum samples collected from the animals. Serum samples from normal or experimental mice cause no shift in the resonance wavelength of the microtoroids; however, after using antibodies toward specific tumor markers to sensitize the toroid surface, we detected changes in the resonance frequency of the microtoroid when exposed to the serum of tumor-implanted mice. Serum from control (tumor-free) mice caused no shift. The wavelength shifts observed were 600 times the noise and drift of the sensor, even for a million fold dilution of the serum sample. Analysis of the shifts showed unitary steps of ∼ 0.5 fm, suggesting that the assay may be sensitive enough to detect individual binding events, offering a means to analyze the size of the biomolecules that are binding to the resonator. If validated, this approach offers a non-invasive tumor “biopsy,” exploiting the circulation of blood to collect a sample of tumor surfaces without the need to find or access the tumors.