High-Q whispering-gallery mode sensor in liquids

Optical sensing of biomolecules on microfabricated glass surfaces requires surface coatings that minimize nonspecific binding while preserving the optical properties of the sensor. Microspheres with whispering-gallery (WG) modes can achieve quality factor (Q) levels many orders of magnitude greater than those of other WG-based microsensors: greater than 10(10) in air, and greater than 10(9) in a variety of solvents, including methanol, H2O and phosphate buffered saline (PBS). The presence of dyes that absorb in the wavelength of the WG excitation in the evanescent zone can cause this Q value to drop by almost 3 orders of magnitude. Silanization of the surface with mercapto-terminal silanes is compatible with high Q (>10(9)), but chemical cross-linking of streptavidin reduces the Q to 10(5)-10(6) due to build-up of a thick, irregular layer of protein. However, linkage of biotin to the silane terminus preserves the Q at a similar to2x10(7) and yields a reactive surface sensitive to avidin-containing ligands in a concentration-dependent manner. Improvements in the reliability of the surface chemistry show promise for construction of an ultrasensitive biosensor.