Label-Free, Single-Molecule Detection with Optical Microcavities
Andrea M. Armani,1
Rajan P. Kulkarni,2
Scott E. Fraser,1,2*
Richard C. Flagan,3*
Kerry J. Vahala1
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 > 108) 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 1012 in concentration, establishing the microcavity as a sensitive and versatile detector.
1 Department of Applied Physics, MC 128-95, California Institute of Technology, Pasadena, CA 91125, USA.
2 Division of Biology, MC 139-74, California Institute of Technology, Pasadena, CA 91125, USA.
3 Division of Chemistry and Chemical Engineering, MC 210-41, California Institute of Technology, Pasadena, CA 91125, USA.
* To whom correspondence should be addressed. E-mail: sefraser{at}caltech.edu (S.E.F.); flagan{at}caltech.edu (R.C.F.)
