Optical Frequency Comb in a Biological Environment

Abstract

The ability to detect individual molecules without the need for labels or capture probes is a topic of great interest in medical applications and scientific research. Frequency-locked microtoroid optical resonators have shown promise in label-free single molecule detection, but currently require prior knowledge of the molecule to be detected and surface functionalization of the cavity. Meanwhile, microresonator-based optical frequency combs have the potential to provide spectral information on molecules, but generating them in aqueous biological sensing environments has been challenging due to altered dispersion, coupling instability, and reduced quality factor of the resonator. In this study, we propose a novel approach to achieve bio-sensing compatible spectroscopy by demonstrating the generation of frequency combs in both water and air at near-visible wavelengths, using a microtoroid optical resonator. Microtoroid resonators are well-suited for biosensing due to their high quality (Q) factors and small mode volumes. We achieve local anomalous dispersion by leveraging the interaction between different transverse mode families within an overall normal dispersion region, while preserving the advantageous structure and material of the microtoroid resonator for biosensing. Our approach can eliminate the need for labels or capture probes and has the potential to enable simultaneous detection and identification of single molecules in both air and liquid at any wavelength. By utilizing microresonator-based frequency combs to measure absorption spectra, we can detect binding events and identify molecular species on the same device, without the need for additional structures or surface functionalization. This has the potential to significantly reduce experimental costs and save time. Despite the advantages of this application, there have been no previous demonstrations of frequency comb generation in a biodetection setting where the resonator is covered with liquid. Conventional dispersion engineering techniques have not been effective in addressing the significant alteration of resonator dispersion caused by an aqueous solution. In this study, we generated an optical frequency comb based on a toroid resonator immersed in high-purity water, using an avoided mode crossing (AMX) approach. We also discuss technical challenges associated with this demonstration and present numerical solutions to overcome them. Overall, our findings can pave the way for label-free single-molecule spectroscopy in aqueous environments using microtoroid resonators. We believe that this approach has promising potential for various biomedical and scientific applications. Further studies are warranted to explore the full potential of this approach in diverse sensing environments and applications.