Iwao Teraoka

Protein detection by optical shift of a resonant microcavity

We present an optical biosensor with unprecedented sensitivity for detection of unlabeled molecules. Our device uses optical resonances in a dielectric microparticle (whispering gallery modes) as the physical transducing mechanism. The resonances are excited by evanescent coupling to an eroded optical fiber and detected as dips in the light intensity transmitted through the fiber at different wavelengths. Binding of proteins on the microparticle surface is measured from a shift in resonance wavelength. We demonstrate the sensitivity of our device by measuring adsorption of bovine serum albumin and we show its use as a biosensor by detecting streptavidin binding to biotin.

Shift of whispering-gallery modes in microspheres by protein adsorption

Biosensors based on the shift of whispering-gallery modes in microspheres accompanying protein adsorption are described by use of a perturbation theory. For random spatial adsorption, theory predicts that the shift should be inversely proportional to microsphere radius R and proportional to protein surface density and excess polarizability. Measurements are found to be consistent with the theory, and the correspondence enables the average surface area occupied by a single protein to be estimated. These results are consistent with crystallographic data for bovine serum albumin. The theoretical shift for adsorption of a single protein is found to be extremely sensitive to the target region, with adsorption in the most sensitive region varying as 1/R(5/2). Specific parameters for single protein or virus particle detection are predicted.

Multiplexed DNA quantification by spectroscopic shift of two microsphere cavities

We have developed a novel, spectroscopic technique for high-sensitivity, label-free DNA quantification. We demonstrate that an optical resonance (whispering gallery mode) excited in a micron-sized silica sphere can be used to detect and measure nucleic acids. The surface of the silica sphere is chemically modified with oligonucleotides. We show that hybridization to the target DNA leads to a red shift of the optical resonance wavelength. The sensitivity of this resonant technique is measured as 6 pg/mm(2) mass loading, higher as compared to most optical single-pass devices such as surface plasmon resonance biosensors. Furthermore, we show that each microsphere can be identified by its unique resonance wavelength. Specific, multiplexed DNA detection is demonstrated by using two microspheres. The multiplexed signal from two microspheres allows us to discriminate a single nucleotide mismatch in an 11-mer oligonucleotide with a high signal-to-noise ratio of 54. This all-photonic whispering gallery mode biosensor can be integrated on a semiconductor chip that makes it an easy to manufacture, analytic component for a portable, robust lab-on-a-chip device.

Perturbation approach to resonance shift of whispering gallery modes in a dielectric microsphere as a probe of a surrounding medium

A first-order perturbation theory similar to the one widely used in quantum mechanics is developed for transverse-electric and transverse-magnetic photonic resonance modes in a dielectric microsphere. General formulas for the resonance frequency shifts in response to a small change in the exterior refractive index and its radial profile are derived. The formulas are applied to two sensor applications of the microsphere to probe the medium in which the sphere is immersed: a refractive index detector; and a refractive index profile sensor.

Theory of resonance shifts in TE and TM whispering gallery modes by nonradial perturbations for sensing applications

A perturbation theory is presented for the frequency shift of highly resonant photonic whispering gallery modes in a transparent sphere. Using a vector wave equation, we derive a general formula for the shifts in TE and TM polarization by adsorption of another dielectric medium. The adsorbed medium can have an arbitrary shape and refractive-index profile. The formula is applied to adsorption of a thin layer and deposition of a small spherical particle, many such particles, and thin cylindrical particles on the resonator surface. We found that the ratio of the TM mode shift to the TE mode shift is sensitive to the shape of the adsorbates and their orientation. Calculation results are discussed in terms of a dipolar field.

MicroParticle photophysics illuminates viral bio-sensing

The authors present an approach for specific and rapid unlabeled detection of a virus by using a microsphere-based whispering gallery mode sensor that transduces the interaction of a whole virus with an anchored antibody. They show theoretically that this sensor can detect a single virion below the mass of HIV. A micro-fluidic device is presented that enables the discrimination between viruses of similar size and shape.

Whispering-gallery modes in a microsphere coated with a high-refractive index layer: polarization-dependent sensitivity enhancement of the resonance-shift sensor and TE-TM resonance matching

Sensitivity enhancement of a whispering-gallery-mode microsphere resonance-shift sensor by coating of a high-refractive index (RI) layer is examined for TM polarization. The enhancement of sensitivity in response to particle adsorption or a RI change of the surroundings at the optimized layer thickness is greater for the TM mode compared with the TE mode, but the TM mode requires a thicker layer. A particular choice of the layer thickness allows the TE and TM shifts to match. Matching of the resonance frequency of the two modes is also examined.

Enhancing sensitivity of a whispering gallery mode biosensor by subwavelength confinement

The authors demonstrate enhanced sensitivity of a spherical whispering gallery mode biosensor (WGMB) by confining orbiting light near the surface using a subwavelength (sub-λ) high refractive index layer on a fluorine doped silica microsphere (radius R∼200μm). Their experiments at a free space wavelength λ∼1310nm show that the frequency shift sensitivity by changing the external refractive index is increased by more than 700% by adding a 340nm thick polystyrene layer. This advance is expected to move the WGMB well into the lead as the most sensitive method for unlabeled biosensing.

Molecular weight dependence of a whispering gallery mode biosensor

We report on molecular weight dependence measurements for an optical resonance biosensor. A dielectric microparticle is evanescently coupled with an optical fiber for the resonance stimulation, and a shift of the resonance wavelength is measured to monitor protein monolayer formation on the microparticle surface. Wavelength shifts for proteins over two orders of magnitude in molecular weight are measured. We show that the shift is proportional to molecular weight to the one-third power. Our result demonstrates that the optical resonance biosensor provides protein size information upon detection. This molecular weight dependency differentiates optical resonance sensing from electrical detection using field-effect transistors.

Theory of dynamics of entangled rod‐like polymers by use of a mean‐field Green function formulation. I. Transverse diffusion

A mean‐field Green function theory is developed for investigating the dynamics of entangled rod‐like polymers in solutions. We regard the hindrance of surrounding rods as a multiple (sequential) perturbation to the free transverse or lateral diffusion of a test rod (a rod in consideration) and incorporate the effects of the perturbation elements one by one into the mean‐field Green function. Thus, an explicit expression for the transverse diffusion constant is obtained as a function of a rod length and a polymer concentration for solutions from dilute to semidilute.