A label-free detection and characterization system includes an optical source; an optical path arranged to be optically coupled to the optical source; an optical resonator disposed proximate the optical path along a side of the optical path, the optical resonator having an optical whispering-gallery mode and being optically coupled to the optical path through an evanescent field to excite the optical whispering-gallery mode; an optical receiver arranged to be optically coupled to the optical path. The optical source is frequency locked to a resonance frequency of the optical resonator and provides light sufficiently intense to provide four-wave mixing while being coupled with the optical resonator resulting in a comb spectrum received by the optical receiver. The comb spectrum provides characteristic changes in the presence of a substance in contact with the optical resonator to provide detection and characterization of the substance.