High-Q whispering-gallery mode sensor in liquids Jay L. Nadeau *a , Vladimir S. Iltchenko **a , Dmitri Kossakovski b , Gregory H. Bearman a , Lute Maleki a a Jet Propulsion Laboratory; b Oewaves, Inc. ABSTRACT 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, H 2 O 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 ~2×10 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. Keywords: whispering-gallery mode; microresonator; streptavidin-biotin; Q factor; evanescent wave; biosensor 1. INTRODUCTION 1.1 Background Optical biosensors are typically transducers that detect the presence of molecules at a surface. They have several desirable features, particularly for the detection of biological molecules: (1) They can be extremely sensitive (nanomoles or less); (2) they are non-destructive to the sample; (3) the transduction processes in optical biosensors generally take place on a surface and can be tailored to sense almost any kind of molecule, chemical and pre-biotic as well as biological. Among the most sensitive class of biosensors are the evanescent wave sensors 1 2 , in which an evanescent wave produced by the total reflection of light within the waveguide interacts with analytes on the waveguide surface. The evanescent wave protrudes above the waveguide surface by ~100 nm (the actual distance depends on the relative index of refraction of the waveguide and the sample medium) and samples only analyte on the surface. Surface treatments such as antibodies or oligonucleotide strands can provide specificity for the analyte; the sensor then detects only that bound to the surface. Transduction mechanisms for bound analyte include fluorescence, mass change in the evanescent region 3 , and change in index of refraction 4 . Typical sensitivity of evanescent wave biosensors based on fiber optic sensors or planar waveguide sensors is in the range of nM to pM. 1.2 Very high Q microspheres Whispering gallery modes of microspherical and other micro-resonators are known to have extremely high quality factors (Q) in the optical domain 5 . Microspherical (50-500 μm diameter) glass resonators with Q’s in excess of 10 10 have been demonstrated, and Q’s as high as 10 11 are, in principle, possible 6 . The very high quality factors Q of microspheres may be attributed to several factors. One is that the dielectric materials for microspheres, fiber grade fused silica, have ultra-low optical loss at the frequencies of the supported whispering gallery modes. Another is that the surface of the sphere is specially fabricated to minimize the size of any surface inhomogeneities, e.g., on the order of a few Å by processes such as fire polishing; these can scatter photons out of the WG mode and decrease the Q 6 . Perhaps mostly important, microspheres have curved circumferential edges above and below their equators to provide a two- dimensional confinement to the optical energy in a WGM for grazing reflection of all wave vector components. This *Jay.L.Nadeau@jpl.nasa.gov; phone 1 818 354-0522; fax 1 818 393-4445; Jet Propulsion Laboratory M/S 183-301, 4800 Oak Grove Dr., Pasadena, CA, USA 91109; **Vladimir.S.Iltchenko@jpl.nasa.gov; phone 1 818 354-8485; fax 1 818 393-6890; Jet Propulsion Laboratory M/S 298, 4800 Oak Grove Dr., Pasadena, CA, USA 91109.