Label-Free, Single-Molecule Detection with Optical Microcavities
Current single-molecule detection techniques require labeling the target molecule. We report a highly specific and sensitive optical sensor based on an ultrahigh quality (Q) factor (Q > 10^8) whispering-gallery microcavity. The silica surface is functionalized to bind the target molecule; binding is detected by a resonant wavelength shift. Single-molecule detection is confirmed by observation of single-molecule binding events that shift the resonant frequency, as well as by the statistics for these shifts over many binding events. These shifts result from a thermo-optic mechanism. Additionally, label-free, single-molecule detection of interleukin-2 was demonstrated in serum. These experiments demonstrate a dynamic range of 10^(12) in concentration, establishing the microcavity as a sensitive and versatile detector.
Additional Information© 2007 American Association for the Advancement of Science. Received 11 May 2007; accepted 14 June 2007; Published online 5 July 2007. We thank O. Painter for useful discussions, B. Min for FEMLAB simulations, N. Pierce for spectrophotometer measurements, and D. Armani for microtoroid fabrication. A.M.A. is supported by the Clare Boothe Luce Postdoctoral Fellowship. This work was supported by the Defense Advanced Research Projects Agency's Center for OptoFluidic Integration and the Biological Imaging Center of the Beckman Institute at the California Institute of Technology.
Errata"Label-free, single-molecule detection with optical microcavities" by A. M. Armani et al. (10 August 2007, p. 783). The authors reported the use of optical microresonators immersed in aqueous solutions and functionalized with antibodies to detect small concentrations of the analytes recognized by the antibodies. The Report presented discontinuities in the resonant response, which the authors took to represent the responses from binding individual analyte molecules. The amplitude of these discontinuities was too large to be caused by the direct effect of the analyte binding; to explain their large size, the authors proposed a thermo-optic effect, in which local heating of the resonator surface from light-analyte interaction amplified the effects of analyte binding. However, as noted by Arnold et al. [Optics Express 18, 281 (2010)], the thermo-optic effect cannot account for the size of the discontinuities. The origin of the large wavelength discontinuities is being investigated by several independent efforts.
Supplemental Material - Armani_SOM.pdf