Protein Detection by Optical Shift of a Resonant Microsphere · 2004-10-14 · A Labview program...

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spheroid optical fiber 100 µm (b) tunable DFB laser diode 1340 nm photodetector sample cell thermocouple optical fiber spheroid 4 mm input coupler (a) (c) L = 30 here: a light orbit in the geo- metrical optics limit light orbit as a wave optics illustration Whispering Gallery Mode in a Dielectric Microsphere Protein Detection by Optical Shift of a Resonant Microsphere Frank Vollmer 1 , Maziar Khoshsima 2 , Dieter Braun 1 , Iwao Teraoka 2 , Albert Libchaber 1 , Stephen Arnold 2 1 Center for Studies in Physics and Biology, The Rockefeller University, New York, NY 10021 email: [email protected] 2 Microparticle Photophysics Lab, Polytechnic University, Brooklyn, NY 11201 www.poly.edu/microparticle We present a novel optical biosensor with unprecedented sensitivity for detection of unlabeled molecules. Our device uses optical resonances in a dielectric micro- particle (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 biosen- sor by detecting streptavidin binding to biotin. An optical resonance (or Whispering Gallery Mode, WGM) occurs when circumnavigating light, trapped by total internal reflection, constructively interfers with itself. Each resonance can be characterized by the number of wavelength L within an orbit. (a) A spheroidal microparticle fabri- cated by melting the tip of a fiber is placed in contact with the eroded part of a single mode optical fiber. The output wavelength of a distrib- uted feedback laser diode is tuned by its laser current. Resonances are detected as dips in the transmitted intensity at different wavelength. Buffer solution is retained in the sample cell due to surface tension, a thermocouple measures the solution temperature. (b) Picture of the spheroid coupled to the optical fiber. (c) Resonances (WGMs) versus wavelength. Proteins binding to the micro- sphere surface increase its effective radius. A given optical resonance will shift its resonance wavelength to accomodate the larger cir- cumverence. BSA solution is injected into the sample cell to a final concentration of 1.5 µM (PBS, pH 7.4). A Labview program traces the wavelength shift of one given opti- cal resonance. The initial negative shift is due to thermal contraction of the spheroid. The overall positive shift is entirely due to BSA adsorption onto the ami- nosilanized microparticle. The inset shows the binding iso- therm. Streptavidin binding to previously surface immobilized BSA-biotin. The initial shift is due to adsorption of BSA-biotin. After injecting Streptavidin, a second shift is observed. λ ... wavelength δλ ... wavelength shift α ex ... excess polarizability of the bound protein σ s ... surface density of the bound protein n 1 , n 2 ... refractive indices of the sphere and the buffer solution, respectively R ... orbital radius ε 0 ... vacuum permittivity FV is supported by a fellowship of the Boehringer Ingelheim Fonds, DB by a Fellowship of the Deutsche Forschungsgemeinschaft, research at the Polytech- nic is supported by a National Science Foundation grant BES-0119273. In the asymptotic limit for the number of wavelength within an orbit L >> 1, the resonance wavelength shift δλ is caused by the energy needed to polarize a protein molecule. The protein needs only be characterized by its excess polariz- ability. The resulting shift is WGMs of a microsphere can be excited by evanescent cou- pling to the core of an optical fiber. Resonances are detected in the scattered light from the microsphere or by dips in the transmitted intensity through the fiber end.

Transcript of Protein Detection by Optical Shift of a Resonant Microsphere · 2004-10-14 · A Labview program...

Page 1: Protein Detection by Optical Shift of a Resonant Microsphere · 2004-10-14 · A Labview program traces the wavelength shift of one given opti-cal resonance. The initial negative

spheroid

optical fiber

100µm

(b)

tunable DFBlaser diode1340 nm

photodetector

sample cell

thermocouple optical fiber

spheroid

4 mm

input coupler

(a)

(c)

L = 30

here:

a

light orbit in the geo-metrical optics limit

light orbit as a waveoptics illustration

Whispering Gallery Modein a Dielectric Microsphere

Protein Detection by Optical Shift of a Resonant MicrosphereFrank Vollmer1, Maziar Khoshsima2, Dieter Braun1, Iwao Teraoka2, Albert Libchaber1, Stephen Arnold2

1Center for Studies in Physics and Biology, The Rockefeller University, New York, NY 10021email: [email protected]

2Microparticle Photophysics Lab, Polytechnic University, Brooklyn, NY 11201www.poly.edu/microparticle

We present a novel optical biosensor with unprecedented sensitivity for detectionof unlabeled molecules. Our device uses optical resonances in a dielectric micro-particle (Whispering Gallery Modes) as the physical transducing mechanism.The resonances are excited by evanescent coupling to an eroded optical fiber anddetected as dips in the light intensity transmitted through the fiber at differentwavelengths. Binding of proteins on the microparticle surface is measured from ashift in resonance wavelength. We demonstrate the sensitivity of our device bymeasuring adsorption of bovine serum albumin and we show its use as a biosen-sor by detecting streptavidin binding to biotin.

An optical resonance (or WhisperingGallery Mode, WGM) occurs whencircumnavigating light, trapped bytotal internal reflection, constructivelyinterfers with itself. Each resonancecan be characterized by the number ofwavelength L within an orbit.

(a) A spheroidal microparticle fabri-cated by melting the tip of a fiber isplaced in contact with the erodedpart of a single mode optical fiber.

The output wavelength of a distrib-uted feedback laser diode is tunedby its laser current. Resonances aredetected as dips in the transmittedintensity at different wavelength.

Buffer solution is retained in thesample cell due to surface tension, athermocouple measures the solutiontemperature.

(b) Picture of the spheroid coupledto the optical fiber.

(c) Resonances (WGMs) versuswavelength.

Proteins binding to the micro-sphere surface increase itseffective radius.

A given optical resonance willshift its resonance wavelengthto accomodate the larger cir-cumverence.

BSA solution is injected into thesample cell to a final concentrationof 1.5 µM (PBS, pH 7.4).

A Labview program traces thewavelength shift of one given opti-cal resonance.

The initial negative shift is due tothermal contraction of the spheroid.The overall positive shift is entirelydue to BSA adsorption onto the ami-nosilanized microparticle.

The inset shows the binding iso-therm.

Streptavidin binding to previously surface immobilized BSA-biotin. The initialshift is due to adsorption of BSA-biotin. After injecting Streptavidin, a secondshift is observed.

λ ... wavelengthδλ ... wavelength shiftαex ... excess polarizability of the bound proteinσs ... surface density of the bound proteinn1, n2 ... refractive indices of the sphere and the buffer solution, respectivelyR ... orbital radiusε0 ... vacuum permittivity

FV is supported by a fellowship of the Boehringer Ingelheim Fonds, DB by aFellowship of the Deutsche Forschungsgemeinschaft, research at the Polytech-nic is supported by a National Science Foundation grant BES-0119273.

In the asymptotic limit for the number of wavelength within an orbit L >> 1,the resonance wavelength shift δλ is caused by the energy needed to polarize aprotein molecule. The protein needs only be characterized by its excess polariz-ability. The resulting shift is

WGMs of a microsphere can be excited by evanescent cou-pling to the core of an optical fiber. Resonances are detectedin the scattered light from the microsphere or by dips in thetransmitted intensity through the fiber end.