This supplementary material provides detailed information on the label-free, single-molecule detection technique using optical microcavities. The ultra-high-Q whispering gallery mode resonators are characterized by long photon lifetimes, which enhance sensitivity in biodetection. The detection mechanism involves the interaction of molecules with the evanescent tail of the whispering gallery mode, leading to a thermo-optic response. The setup includes a single-mode, tunable external cavity laser coupled to a tapered optical fiber waveguide, which is used to probe the resonant cavity. The microtoroids are placed in a water-filled microaquarium, and the resonant wavelength and Q factor are monitored to detect molecular binding events. The sensitivity of the detection is demonstrated through experiments with Interleukin-2 (IL-2) and other biological molecules, including Cy5-labeled antibodies. The material also discusses the thermal stabilization of the microcavities, statistical analysis of binding events, and the photo-bleaching of fluorescent labels. The findings highlight the potential of this technique for label-free, single-molecule detection in complex environments.This supplementary material provides detailed information on the label-free, single-molecule detection technique using optical microcavities. The ultra-high-Q whispering gallery mode resonators are characterized by long photon lifetimes, which enhance sensitivity in biodetection. The detection mechanism involves the interaction of molecules with the evanescent tail of the whispering gallery mode, leading to a thermo-optic response. The setup includes a single-mode, tunable external cavity laser coupled to a tapered optical fiber waveguide, which is used to probe the resonant cavity. The microtoroids are placed in a water-filled microaquarium, and the resonant wavelength and Q factor are monitored to detect molecular binding events. The sensitivity of the detection is demonstrated through experiments with Interleukin-2 (IL-2) and other biological molecules, including Cy5-labeled antibodies. The material also discusses the thermal stabilization of the microcavities, statistical analysis of binding events, and the photo-bleaching of fluorescent labels. The findings highlight the potential of this technique for label-free, single-molecule detection in complex environments.