Optical Biosensor based on Whispering Galery Mode Technology

Optical biosensors capable of detecting unlabelled molecules have become valuable tools in life sciences as well as in drug discovery over the last 10 years. Vollmer et al., (2002) provided proof-of-principle for a biosensor, claimed to have unprecedented sensitivity for molecular detection that exploited shifts in optical resonances in a single transparent dielectric microparticle (specifically a 300 mm diameter spherical glass bead) to detect adsorption of bovine serum albumin protein deposition. The potential of the system for immunosensor type applications was demonstrated by detection of streptavidin binding to the biotin-coated surface of a microsphere. The group went on to show theoretically that microspheres as small as 7.2 mm diameter could be effectively exploited for protein detection and that the system was particularly sensitive to protein adsorbing at particular locations on the microsphere surface (Arnold et al., 2003). The theoretical understanding of the sensitivity of the whispering-mode system is also progressing (Teraoka et al., 2003). Double microsphere systems were shown to allow for multiplexed DNA quantification (Vollmer, Arnold et al, 2003) Also micro-disc resonators using the same detection principle were predicted to be sensitive (Boyd et al., 2001) , and polystyrene micro-ring resonators were shown to have a high sensitivity as chemical (glucose) adsorption sensors (Chao et al., 2003). The sensitivity of adsorption bioassays can be improved by ultrasonic surface wave excitation (Wang et al., 1999). The effect is attributed to streaming induced at the transducer fluid interface. The streaming patterns at a sensing surface in a quarter wavelength bulk acoustic wave resonator have recently been characterised by particle image velocimetry techniques. Induction of small Rayleigh type vortices was observed at many points (Kuznetsova and Coakley, 2004). Three-fold enhancement of the immuno-capture of 200nm fluorescent latex particles (a size so small that acoustic streaming rather than radiation pressure would be solely responsible for increased adsorption) provides promising data (Kuznetsova et al., in preparation) on how molecular adsorption might also be enhanced by streaming. Aims Detect and characterise whispering modes from individual antibody-coated dielectric microspheres. Measure the change in resonance frequency of the mode as antigen is adsorbed to the dielectric microspheres. Devise a system for holding and sensing an array of dielectric microspheres for parallel optical interrogation of many antigens. Devise a system to incorporate acoustic streaming currents in the assay chamber to improve the detection speed and sensitivity.

From Arnold et al. Optics Letters 28,272 (2003), Fig.1: Nanoscopic protein molecule at position ri on the surface of a sphere near an eroded optical fiber core. The sphere and fiber are surrounded by an aqueous solution.

References:

• Vollmer F, Braun D, Libchaber A, Khoshima M, Teraoka I and Arnold S. (2002) Protein detection by optical shift of a resonant microcavity. Appl. Phys. Lett. 80:4057-4059.
• Arnold S, Khoshima M, Teroaka I, Holler S, Vollmer F (2003). Shift of the whispering-gallery modes in microspheres by protein adsorption. Opt. Lett. 28:272-275.
• Teraoka I., Arnold S, Vollmer F (2003) Perturbation approach to resonance shifts of whispering gallery modes in a dielectric microsphere as a probe of a surrounding medium. J. Opt. Soc. Am. B 20: 1937-46
• Vollmer F, Arnold S, Braun D,Teraoka I, Libchaber A (2003), Multiplexed DNA Quantification by Spectroscopic Shift of Two Microsphere Cavities, Biophys. J. 85 1974–1979
• Chao C-Y, Guo LJ (2003) Biochemical sensors based on polymer microrings with sharp asymmetrical resonance. Appl. Phys. Lett. 83:1527-1529.
• Boyd, RW, Heebner, JE (2001) Sensitive disk resonator photonic biosensor, Appl. Optics 40:5742-7
• Kuznetsova LA, Coakley WT (2004). Microparticle concentration in short path length ultrasonic resonators: Roles of radiation pressure and acoustic streaming. J. Acoust. Soc. Am. In press.

Project Members

• Julie Lutti (PHYSX)
  
• Wolfgang Langbein (PHYSX)
• Paola Borri (BIOSCI)
• Terence Coakley (BIOSCI)
• Martin McDonnel (DSTL)