Label-Free, Single-Molecule Detection with Optical Microcavities

TLDR

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 > 10⁸) whispering‑gallery microcavity. The sensor uses a silica‑functionalized whispering‑gallery microcavity whose binding events produce thermo‑optic resonant wavelength shifts. The device achieves label‑free single‑molecule detection, demonstrated with interleukin‑2 in serum and a 10¹²‑fold dynamic range.

Abstract

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.