Frequency Locked Optical Whispering Evanescent Resonator: Fundamentals and Applications

Abstract

Label-free, sensitive and rapid biochemical sensors have been expanding due to the need for a wide range of applications including early diagnostics and early detection of hazardous gases. Whispering gallery mode (WGM) microtoroid resonators are one of the most sensitive sensors at present. When combining WGM microtoroid resonators with frequency locking, balanced detection, and data analysis, they can detect zeptomolar protein concentrations within a few seconds and are able to detect hazardous gases at low part-per-trillion concentration levels. An accurate analysis of the analyte delivery to sensor is important to optimize system performance and data analysis. We visualized analyte transport to a toroidal resonator through the color transition of bromothymol blue and combined this with finite element simulation data to examine the analyte arrival time and study its mechanism. This will enable better system design and data analysis in the future. We found that the collision time for 1 fM solution with a diffusion coefficient of 150 〖μm〗^2/s is in the range of 10-20 s and the analyte is detectable under a minute after injection considering both the analyte delivery and collision time.Light is typically coupled to microtoroid optical resonators through a tapered optical fiber. At the resonance condition, the light in every revolution returns in phase, resulting in constructive interference. In biochemical sensing experiments, the target analytes are immobilized to the cavity’s surface through surface functionalization. The existence of the bound analytes perturbs the evanescent field extending from the cavity, inducing a change in effective refractive index which is then detected through a shift in resonance frequency. Frequency locking techniques are used to track the resonance shift. Here, we used frequency locked optical whispering evanescent resonator (FLOWER) to evaluate the drug candidate performance to prevent spike protein of SARS-CoV-2 to bind with human receptor (hACE2). We found that methotrexate not only inhibits the replication and release of the virus, as previously found, but also blocks the virus from entering cells. Even though tapered fiber coupling can provide high coupling efficiency in excess of 99%, it hinders the translation of devices to field use. Here, we developed a free space coupling system using a single long distance objective lens. Q-factors as high as 1.6×10^8 were achieved. We found that using a higher numerical aperture objective lens provides higher coupling efficiency, but less tolerance to the mechanical vibration. The sensing application was verified by performing temperature sensing experiments. We believe that this work will be a foundation of fully on-chip WGM microtoroid resonator and can expand the application of the system; for example, to be able to multiplex.