  The ability to detect and identify molecules at high sensitivity without the
use of labels or capture agents is important for medical diagnostics, threat
identification, environmental monitoring, and basic science. Microtoroid
optical resonators, when combined with noise reduction techniques, have been
shown capable of label-free single molecule detection, however, they still
require a capture agent and prior knowledge of the target molecule. Optical
frequency combs can potentially provide high precision spectroscopic
information on molecules within the evanescent field of the microresonator;
however, this has not yet been demonstrated in air or aqueous biological
sensing. For aqueous solutions in particular, impediments include coupling and
thermal instabilities, reduced Q factor, and changes to the mode spectrum. Here
we overcome a key challenge toward single-molecule spectroscopy using optical
microresonators: the generation of a frequency comb at visible to near-IR
wavelengths when immersed in either air or aqueous solution. The required
dispersion is achieved via intermodal coupling, which we show is attainable
using larger microtoroids, but with the same shape and material that has
previously been shown ideal for ultra-high sensitivity biosensing. We believe
that the continuous evolution of this platform will allow us in the future to
simultaneously detect and identify single molecules in both gas and liquid at
any wavelength without the use of labels.
