WO2008152367A1 - Dispositif de détection optique - Google Patents

Dispositif de détection optique Download PDF

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Publication number
WO2008152367A1
WO2008152367A1 PCT/GB2008/001966 GB2008001966W WO2008152367A1 WO 2008152367 A1 WO2008152367 A1 WO 2008152367A1 GB 2008001966 W GB2008001966 W GB 2008001966W WO 2008152367 A1 WO2008152367 A1 WO 2008152367A1
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WIPO (PCT)
Prior art keywords
microsphere
coupler
refractive index
separation layer
diameter
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PCT/GB2008/001966
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English (en)
Inventor
Paola Borri
Wolfgang Langbein
Julie Lutti
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The Secretary Of State For Defence
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Publication of WO2008152367A1 publication Critical patent/WO2008152367A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N2021/7769—Measurement method of reaction-produced change in sensor
    • G01N2021/7789—Cavity or resonator

Definitions

  • the present invention is directed to an optical sensing device comprising a microsphere optical resonator and to a sensing chip comprising the same.
  • Optical biosensors provide a superior method for the detection of these pathogens in that they allow real time monitoring of an environment according to changes in an optical property associated with a biological sample.
  • Such sensors are commonly based on optical structures in which an evanescent wave associated with an optical mode existing in the structure extends into a sensing layer comprising the biological sample.
  • evanescent sensors examples include surface plasmon resonance (SPR) sensors, resonant mirror (RM) sensors and metal- or dye-clad leaky waveguide (M/DCLW) sensors.
  • SPR surface plasmon resonance
  • RM resonant mirror
  • M/DCLW metal- or dye-clad leaky waveguide
  • a new biosensor based on near field (evanescent) coupling of light from an eroded optical fibre to an optical resonator comprising a dielectric microsphere has recently been reported (Vollmer, F. et al., Appl. Phys. Lett., 2002, 80, 4057-4059).
  • the resonant optical modes (whispering gallery modes, WGM) generated in the microsphere are confined close to its surface by repeated total internal reflection and, in turn, lead to an associated evanescent field.
  • the binding of a target analyte to the microsphere is detected by a change in the resonance wavelength of the biosensor.
  • the new biosensor is much more sensitive than the planar surface biosensors mentioned above because the light within the microsphere can orbit many thousands of times before coupling back into the fibre.
  • the sensitivity of the technique can be related to the quality of the resonance (the "Q- factor") of the microsphere, a measure common to all resonators which expresses the rate of loss of power (damping).
  • biosensor detection of nucleic acids (Vollmer, F. et al., Biophys. J., 2003, 85, 1974-1979), proteins (Arnold, S. et al., Optics Letters, 2003, 28(4), 272-274 and Noto, M. et al., Appl. Phys. Lett., 2005, 87, 223901) and characterisation of nanolayer formation (Noto, M, et al., Optics Letters, 2005, 30(5), 510-512) and photo- induced molecular transformations (Topolancik, J. and Vollmer, F., Biophys. J., 2007, 92, 2223-2229).
  • nucleic acids Vollmer, F. et al., Biophys. J., 2003, 85, 1974-1979
  • proteins Arnold, S. et al., Optics Letters, 2003, 28(4), 272-274 and Noto, M. et al., Appl. Phys. Lett.,
  • the present inventors have now determined that high intrinsic Q factors, not limited by evanescent field coupling back to the substrate, are obtainable from WGMs of microspheres held in aqueous buffer at predetermined distances from planar surface couplers.
  • the present invention provides an optical sensing device comprising an optical resonator; a planar surface, near field coupler for coupling evanescent light to the resonator; and fixing means for positioning the resonator relative to the coupler, in which the resonator comprises a microsphere having refractive index 1.50 to 1.95 and diameter 5 to 100 ⁇ m and is positioned adjacent the planar surface of the coupler with a separation gap of 200 to 2000 run.
  • planar surface, near field coupler refers to a coupler in which the frustrated total internal of light is incident at a planar surface.
  • the microsphere in order that the device function as a high Q factor optical resonator the microsphere must comprise a dielectric material having low extinction of light.
  • Suitable materials include, but are not limited to, polystyrene and glass, the latter being preferred because it can have lowest extinction of light. Suitable diameters and separation (gap) distances will depend on the refractive index of the material as well as that of the surrounding medium.
  • suitable diameters for microspheres comprising polystyrene (refractive index 1.58) for use in aqueous solution may be 25 to 45 ⁇ m, 20 to 30 ⁇ m, 25 to 30 ⁇ m, or 30 to 40 ⁇ m.
  • suitable diameters for microspheres comprising glass (refractive index 1.52) for use in aqueous solution may be 50 to 60 ⁇ m.
  • Suitable separation distances for use with polystyrene microspheres are, for example, 200 to 600 run, more particularly, 300 to 400 nm or 400 to 600 nm.
  • Suitable separation distances for glass microspheres are 600 to 800 nm and preferably 700 to 800 nm.
  • the near field coupler may, in particular, comprise a prism, lens or waveguide coupler but other planar surface couplers may also be suitable.
  • the near field coupler comprises a half ball lens.
  • the refractive index of the half ball lens is greater than that of water. In one embodiment, it is 1.825 but other values above 1.33 will also be suitable, provided that an efficient coupling exciting WGMs is obtainable at convenient angles above the critical angle.
  • the near field coupler includes a monochromatic light source, which can be mechanically swept across a range of angles above the critical angle for total internal reflection.
  • the light source is a laser (wavelength 700 to 900 nm) which can be tuned to provide a suitable wavelength for measuring the reflectivity spectrum.
  • the reflectivity spectrum is measured by tuning the wavelength of the laser and that the minimum detectable line width in the reflectivity spectrum is dictated by the line width of the laser.
  • the light source comprises a tuneable laser of line width about one twenty fifth of the WGM resonance line width found in the reflectivity spectrum
  • the laser may comprise a tuneable DFB laser emitting at a wavelength of ⁇ 770 nm (corresponding to photon energy of ⁇ 1.60 eV).
  • the fixing means may comprise any means for positioning the microsphere above, but not in contact with, the planar surface of the coupler. Suitable fixing means known to those skilled in the art include optical tweezers or an x-y-z mechanical stage.
  • the microsphere is formed with an integral stem portion by, for example, burning an optical fibre end in a butane/nitrous oxide flame.
  • An aspect of the present invention provides for a novel optical tweezers arrangement.
  • the tweezers enable the microsphere to be held in aqueous solution at a chosen distance above the upper surface of the coupler.
  • optical trapping force is (according to geometric optics) increased in this arrangement by a factor of two compared with a full cone illumination having the same maximum aperture angle and power.
  • the ring illumination facilitates the use of a standard oil immersion objective for trapping in water by reducing the impact of the spherical aberrations created by the refractive index mismatch (between water and the oil in which the objective is immersed).
  • a cone angle of 64° and a trap optical power of 250 mW holds a polystyrene microsphere of diameter 15 to 40 ⁇ m through 80 ⁇ m distance in water against the action of gravity (see Figure 1).
  • Thermal position fluctuations along the axial trapping direction are small compared with the WGM evanescent field decay length (20 to 25 run; RMS) and the trap can, therefore, precisely control the distance of the microsphere from the planar surface coupler.
  • the microsphere is positioned in relation to the near field coupler so that the whole or at least a major portion thereof overlaps with the planar surface.
  • the present invention provides for fixing means comprising a transparent separation layer of refractive index matched to a sensing medium, which is provided to the planar surface of the coupler and to which the microsphere is adhered.
  • sensing medium refers to the medium which is to be interrogated by the device.
  • the sensing medium is water, or an aqueous solution, and the separation layer has a refractive index about 1.33.
  • the refractive index of the separation layer is similar to that of the sensing medium is so that the layer does not interfere with WGMs of the microsphere in the medium.
  • Matching of the refractive index of the separation layer and the refractive index of the surrounding medium maximises the Q-factor that can be achieved. It has been found, however, that the refractive index need not be identical and that small deviations from the actual value of solution are acceptable.
  • the separation layer comprises a cured polymer since the (thermal or optical) curing process enables direct adherence of the microsphere.
  • a particularly, suitable polymer comprises a co-polymer of perfluoro alkenyl vinyl ethers, such as CYTOP® (for example, CT-SOLV 180, CTL-809A, CT-PlO; Ashahi Glass Co. Ltd.) which has a refractive index of 1.34.
  • CYTOP® for example, CT-SOLV 180, CTL-809A, CT-PlO; Ashahi Glass Co. Ltd.
  • the CYTOP® separation layer can be spin coated to the lens, prism or waveguide or to a glass plate which is or can be arranged for optical matching with the lens, prism or waveguide.
  • the separation layer comprises an inorganic material such as magnesium fluoride (MgF 2 , refractive index 1.36). Glass slides coated with this material are commercially available.
  • MgF 2 magnesium fluoride
  • the separation layer includes a layer or spot of a transparent adhesive to which the microsphere is adhered.
  • the refractive index of the transparent adhesive may be similarly matched to the target medium.
  • the adhesive may be a UV-curable adhesive so as to enable spot adhesion of a microsphere positioned by optical tweezers by focusing light with a microscope or by illumination parallel to the separation layer.
  • the uncured adhesive is subsequently washed away with an appropriate solvent.
  • Suitable transparent adhesives for this purpose comprise CYTOP® and a polyacrylate adhesive, which is available under the proprietary name, DeIo Photobond 4436.
  • the microsphere may alternatively be adhered by thermal curing of a layer or spot of adhesive comprising or consisting the material in the separation layer, for example CYTOP®.
  • a layer or spot of adhesive comprising or consisting the material in the separation layer, for example CYTOP®.
  • 50 ⁇ m glass microspheres may be adhered to a cured CYTOP® separation layer through further thermal curing, thus softening the layer, and allowing the microspheres to penetrate/sink into the layer to the desired depth.
  • Polystyrene microspheres may be adhered to a surface by spin coating a second layer onto the surface, prior to deposition of the microspheres, followed by a curing step.
  • the thickness of the separation layer is chosen for a particular microsphere so as to meet the aforementioned requirements for sharp resonances in the reflectivity spectrum.
  • the separation layer offers a practical chip for use with planar surface near field couplers (see later) and avoids the problem of fluctuation in the amplitude of resonances over time (so called "jitter”) in the reflectivity spectrum found for microspheres in optical tweezers.
  • This jitter is attributed to rotation of the microsphere in the optical tweezers and the fact that the microsphere is imperfectly spherical - leading to changing coupling strength to WGMs with time.
  • the thickness of the separation layer may be 400 to 600 nm.
  • the separation layer may have thickness 600 to 800 nm and adhere a glass microsphere (refractive index 1.52) having diameter 40 to 50 ⁇ m.
  • the separation (and adhesive) layer has thickness 250 to 350 nm and adheres a glass microsphere (refractive index 1.92) having diameter 5 to 15 ⁇ m.
  • the microsphere is coated with a specific recognition element for a target analyte.
  • the specific recognition element may, for example, comprise an antibody, hapten or a nucleic acid.
  • the specific recognition element may be attached to the microsphere by any suitable covalent and/or electrostatic chemistry.
  • glass microspheres may be derivatised by silanisation and subsequent functionalisation permitting the attachment of a coating of antibody, hapten or nucleic acid.
  • the microsphere will be coated following its adherence to the separation layer but it is envisaged that provided the coating survives, for example, the thermal curing of the separation layer and/or adhesive, it may be coated prior to its adherence.
  • the glass microspheres may, for example, bear a carboxylic or amine functionality which can be derivatised following adherence to the separation layer by conventional chemical methods so as to permit attachment of the specific recognition element.
  • the device is associated with a flow cell and pump means providing for the passage of a sensing medium, for example aqueous buffer, over the planar surface or separation layer of the device.
  • a sensing medium for example aqueous buffer
  • the present invention provides for a sensing chip for use with a near field coupler, comprising a surface planar, glass or waveguide substrate provided with a separation layer having a refractive index matched to that of a sensing medium and thickness 200 to 2000 nm, to which an optical resonator comprising a microsphere having refractive index 1.50 to 1.95 and diameter 5 to 100 ⁇ m is adhered.
  • the present invention also envisages a device comprising a near field coupler including a single chip provided with a plurality of waveguides each having a microsphere coated with a specific recognition element which is different to any other.
  • the chip may comprise a plurality of waveguides providing coupling of an evanescent field to the microspheres at different wavelengths of incident light.
  • the chip may comprise a single waveguide provided with a plurality of microspheres each coated with a specific recognition element different to any other, which is associated with a linear photodectector array.
  • the chip includes an uncoated microsphere as a reference function to allow fluctuations in the refractive index not due to target analyte to be taken into account.
  • the device may be used for multiplex detection in conjugation with a tuneable (wavelength) laser by, for example, measurement of the intensity coupled to the WGMs as a function of wavelength or of the intensity of scattering in the upper hemisphere of the microsphere.
  • the target analyte is not limited by the present invention, but preferably comprises a protein, nucleic acid, bacterium, spore or virus.
  • Figure 1 is a scheme showing a device according to one embodiment of the present invention.
  • Figure 2 is a graph showing the reflectivity spectrum obtained with the device of Figure 1 on a polystyrene microsphere of diameter 30 ⁇ m;
  • Figure 3 is a graph showing the variation in line width of a resonance peak in the reflectivity spectrum obtained with the device of Figure 1 on a polystyrene microsphere of diameter 28 ⁇ m with its distance from the coupler;
  • Figure 4 is a graph showing fine structure in a resonance peak of the reflectivity spectrum of Figure 2;
  • Figure 5 is a schematic representation of a substrate or chip provided with a polymer separation layer and an adhesive layer fixing a polystyrene microsphere;
  • Figure 6 is graph showing the change in the reflectivity spectrum of the device of
  • Figure 7 is a graph showing the change in the reflectivity spectrum of a device over time according to Figure 1 in response to a solution of streptavidin (0.1 mg/L);
  • Figure 8 is a graph showing part of the reflectivity spectrum of a device according to Figure 1 incorporating a substrate provided with a separation layer;
  • Figure 9 is a graph showing the change in the reflectivity spectrum of Figure 8 to fluctuations in the refractive index of an aqueous sample
  • Figure 10 is a graph showing the change in the reflectivity spectrum over time of a device similar to that of Figure 1 incorporating a substrate according to Figure 5;
  • Figure 11 is a graph showing relating the graph of Figure 10 to the centre peak energy of a particular resonance peak.
  • Figure 12 a) and b) are graphs showing the theoretical relationship of responsivity to line width for a variety of microsphere refractive index detected through polarisations coupled to a) the TE mode of the microsphere and b) the TM mode of the microsphere.
  • the diameter of the beads are, from left to right 12 to 6 ⁇ m (1.9), 25 to 10 ⁇ m (1.68), 45 to 20 ⁇ m
  • Figure 13 is a graph showing TE and TM polarised reflectivity spectra for an embodiment of the invention comprising a polystyrene bead (44 ⁇ m) glued to a Cytop® layer.
  • Figure 14 is a graph showing TE polarised reflectivity spectra, with TM polarisation used as reference, for an embodiment of the invention comprising a polystyrene bead (44 ⁇ m) glued to a Cytop® layer.
  • Figure 15 is a graph showing the change in resonance energy against glycerol concentration for one embodiment of the present application.
  • FIG. 1 there is shown a schematic representation of a device according to one embodiment of the present invention.
  • the device generally designated 10, includes a transparent flow chamber 11 which together with the upper surface of the coupler defines a conduit of width 80 ⁇ m and pumps for controlled delivery of aqueous sample (not shown).
  • the annular beam profile is created from a TEMo 0 mode of Nd: YAG laser 14 of wavelength 1064 nm by a pair of axicons 15.
  • the optical tweezers use a cone angle of 64° and an optical trap power of 250 mW to trap a polystyrene bead 16 of diameter 15 to 40 ⁇ m in water within the flow chamber.
  • the position of the high NA objective is controlled by a precision mechanical stage (not shown).
  • the near field coupler generally designated 1OB, comprises a tuneable DFB laser 17 emitting at a wavelength of ⁇ 770 nm, corresponding to photon energy ⁇ 1.60 eV, a high refractive index (1.83) half ball lens 18 and a photodiode detector array and spectrograph 19.
  • the coupler also includes means for selecting the polarisation of light 20 in the incident and reflected light beam 21.
  • the spot Gaussian beam diameter of ⁇ 5 ⁇ m and the excitation angle ⁇ ⁇ 55° are adjusted for good field overlap with the WGMs at the surface.
  • the WGM resonances are detected as dips in the measured reflectivity spectrum.
  • Horizontal and vertical (z) polarisations are detected simultaneously, which couple respectively to the transverse magnetic (TM) and transverse electric (TE) modes of the microsphere.
  • DFB laser under threshold provides for a spectrally broad amplified spontaneous emission which is used for the excitation of WGMs over a spectral range of up to 25 meV.
  • the reflection is dispersed by a high resolution ( ⁇ 5 ⁇ eV) grating spectrometer and detected by a cooled CCD camera.
  • the DFB laser emission is ultra-narrow (0.02 ⁇ eV) and can be temperature tuned over a range of 5 meV as well as rapidly scanned over a range of about 100 ⁇ eV using a triangular current modulation at about 50 Hz.
  • the detection uses two photodiodes and an oscilloscope to measure the difference between the vertically and horizontally polarised reflected intensities.
  • a combination of ⁇ /2 and ⁇ /4 plates can be used to selectively excite and detect TE and TM polarised WGMs. Exciting both polarisations simultaneously and using a balanced detection scheme enables the resonant transmission to be measured in both intensity and phase. This interferometric detection provides a background free dispersive spectral line shape of half the mode line width.
  • the inset image of Figure 1 shows a trapped microsphere coupled to the excitation beam.
  • FIG. 2 there is shown a graph of the reflectivity spectrum measured on the polystyrene microsphere (Polysciences Inc.; diameter 24 to 31 ⁇ m) held in aqueous buffer (purified water; Triton X-100 at 1 x 10 "4 v/v) at a distance of about 300 run above the substrate.
  • aqueous buffer purified water; Triton X-100 at 1 x 10 "4 v/v
  • the mode order n and mode number / of the WGM resonances are determined by comparison to the explicit asymptotic formulae of Mie theory (see Lam CC, et al., in J. Opt. Soc. Am. B, 1992, 9, 1585).
  • the signal broadens (and deepens) as the microsphere is brought closer to the substrate - indicating stronger coupling to the excitation beam and other substrate optical modes.
  • the line widths are not Lorentzian but instead consist of an ensemble of dips - attributed to lifting of the degeneracy of the 2/ + 1 azimuthal modes due to imperfectly spherical microsphere.
  • the high resolution spectrum of Figure 4 shows this lifting of degeneracy for a TEl mode in the microsphere of Example 1 (distance from substrate 700 nm). While the microsphere rotates freely in the optical trap the spatially localised excitation couples for different rotation angles to different sub-ensembles of modes which are solidal to the microsphere so that the weight of different modes in the reflectivity spectrum changes with time.
  • jitter This effect, referred to previously as jitter, is clearly seen in the inset figure, which is a graph of the reflectivity spectrum as a function of time on a grey scale from 1 (white) to 0.96 (black).
  • the observed oscillatory structure is attributed to a cyclic rotation dynamics of the sphere induced by residual flow of the surrounding sample.
  • the total spectral width of the measure mode ensemble of individual TE n ; or TM n/ resonances was typically less than 200 ⁇ eV which corresponds to an asphericity of the microsphere in the 1 x 10 "4 range.
  • this Q-factor is largely attributable to intrinsic Q-factor because high Q- loading by the coupler at this distance means a very small line width attributable to the substrate.
  • the intrinsic Q-Factor of a 30 ⁇ m diameter polystyrene microsphere in water in the Mie theoretical limit is 1.5 x 10 8 .
  • the high intrinsic Q-factor of a 30 ⁇ m diameter polystyrene microsphere held in aqueous buffer by optical tweezers suggests sensitivity to a change in the refractive index of the surrounding medium of as little as 4 x 10 " (line width of DFB laser is 1.6 x 10 " eV).
  • Example 3 Referring now to Figure 6, there is shown a graph of the reflectivity spectrum as a function of time measured on a polystyrene microsphere of diameter 25 ⁇ m held by optical tweezers at a distance 300 nm above the substrate.
  • the difference in refractive index of the glycerol solution over aqueous buffer is 0.00743.
  • one embodiment of the present invention comprises a device in which a separation layer generally designated 22 of CYTOP® 23 is provided to the half ball lens 18 substrate of the coupler.
  • the separation layer includes an adhesive overlay 24 to which the microsphere 16 is adhered.
  • the line widths are between 0.7 and 1 ⁇ eV - corresponding to Q-factors of 2.3 x 10 6 and 1.6 x 10 6 .
  • Figure 9 reports a shift of 66 ⁇ eV in the reflectivity spectrum over a time interval of 34 minutes which is attributed to temperature drift and/or binding of surfactant. The shift suggests the sensitivity of the device to be similar to that mentioned above.
  • the coated half ball lens was used in a device similar to that described in relation to Figure 1, but without optical tweezers.
  • soda lime glass beads were able to withstand a flow of liquid at 125 mm s "1 over the surface of the sensing device, and did not show mode jumping, thus overcoming a major limiting factor of microspheres held by optical tweezers which are free to rotate.
  • the measured line width of this resonance is ⁇ 70 ⁇ eV, which corresponds to a Q-factor of ⁇ 2.3 x 10 4 .
  • the graph shows a shift in the resonance peak of 183 ⁇ eV (see Figure 11), when a 5% solution of glycerol in water is progressively introduced in to the flow cell (flow rate 50 ⁇ l/sec).
  • the fixing of the microsphere without rotation in optical tweezers or due to sample flow substantially removes jitter.
  • the present inventors have shown sharp WGMs resonances in the reflectivity spectrum of microspheres held in aqueous sample which are attributable to high intrinsic Q.
  • a microsphere should have a high responsivity and produce sharp resonances (small linewidths).
  • Soda lime glass beads (refractive index 1.51) and polystyrene (refractive index 1.31) should have a high responsivity and produce sharp resonances (small linewidths).
  • Soda lime glass beads (refractive index 1.51) and polystyrene (refractive index 1.31) should have a high responsivity and produce sharp resonances (small linewidths).
  • soda lime glass beads have a slightly higher responsivity than polystyrene at a particular linewidth for TE polarisation. Soda lime glass beads also offer the advantage of a known chemistry for surface functionalisation.
  • Figure 12 b) also shows that TM polarisation corresponds to higher responsivity than TE polarisation.
  • An alternative method for attaching soda lime glass beads to the separation layer investigated removal of the adhesive or glue layer and placing the bead directly onto the cured separation layer of Cytop®, followed by a re-curing step at a lower temperature.
  • Bead attachment was studied as a function of time and temperature, and the strength of attachment tested against a controlled liquid flow. The depth of attachment was tested by measuring the 'footprint' using a light microscope.
  • Optimum re-curing conditions were found to be at a temperature of between 15O 0 C and 175°C for a period of about 10 min. Strong attachment and sinking of the bead by less than 200 nm was achieved.
  • Polystyrene beads have sufficient surface quality to achieve improved Q factors to about 4 x 10 6 .
  • polystyrene beads have a similar glass transition temperature to materials in the separation layer, i.e. Cytop® (glass transition temperature of Cytop® is 108 0 C and of polystyrene is approximately 100 0 C)
  • adherence of polystyrene beads to the separation layer through temperature curing is limited.
  • Adherence of dried polystyrene beads through curing onto a cured Cytop® layer at 125 0 C for 13 min resulted in the beads often not attaching or partial melting of polystyrene and/or intermixing with Cytop®.
  • the optimised procedure as a compromise between adherence strength and preservation of bead optical quality was spin- coating and high temperature curing (18O 0 C) of Cytop® separation layer (thickness between 200 nm and 800 nm), spin-coating of Cytop® 'glue' layer (thickness between 100 nm and 200 nm), addition of beads in water onto the soft 'glue' layer, and temperature curing at 115 0 C for lO mins.
  • R/Ro for the glued polystyrene beads (44 ⁇ m) on the Cytop® separation layer is dependent on the angle of incidence of the coupling angle and on the mode order (n) of the bead, with the higher angles selectively exciting the smaller n order modes.
  • the resonance position of the bead in the sensor of example 10 was monitored whilst flowing glycerol solutions of various concentrations through the sensor, at an acquisition rate of 1 Hz.
  • the refractive index change with glycerol concentration is 1.38E “3 ⁇ 2E 4 RIU per %vol. From the measured variation of the resonance position of 3.0785E “5 ⁇ 2E “8 eV per %vol, we obtain a responsivity of -22 ⁇ 2 meV per RIU.
  • the precision of the peak energy from fitting a single spectrum acquired in 18 ms is 1 neV, corresponding to a sensitivity of 5 x 10 "8 RIU (for comparison, the sensitivity of a Biacore instrument was calculated from measured data to be 1.5 x 10 ⁇ 7 RIU at an acquisition rate of 1 Hz).
  • the standard deviation of the fitted resonance peak energy is 30 neV. This value is limited by the jitter of the optical excitation wavelength which is caused by instability of the DFB laser diode temperature and fast fluctuations in the laser diode current.
  • This precision results in 1.4 x 10 ⁇ 6 in terms of minimum detectable refractive index change, and 0.7 pg/mm or 4 fg in terms of molecular mass coverage.
  • the sensitivity of the sensor may be improved by increasing the responsivity of the sensor, which could be achieved by reducing the diameter of the polystyrene beads and by using TM polarisation, as shown in Figure 12 a) and b). This could improve the responsivity by a factor of 2.
  • the jitter could be reduced by optimising the DFB laser diode temperature control. Jitter could also be reduced by using a reference bead having resonances sufficiently close in energy to be scanned by the DFB laser in a single scan. However, fast fluctuations in the DFB laser diode current, also responsible for the jitter, cannot be cancelled by referencing.

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Abstract

L'invention porte sur un dispositif de détection optique comprenant un résonateur optique; une surface plane, un coupleur à champ proche pour coupler une lumière évanescente au résonateur; et des moyens de fixation pour positionner le résonateur par rapport au coupleur, le résonateur comprenant une microsphère ayant un indice de réfraction de 1,50 à 1,95 et un diamètre de 5 à 100 µm et étant positionné adjacent à la surface plane du coupleur avec un intervalle de séparation de 200 à 2000 nm.
PCT/GB2008/001966 2007-06-15 2008-06-11 Dispositif de détection optique WO2008152367A1 (fr)

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GBGB0711600.7A GB0711600D0 (en) 2007-06-15 2007-06-15 An optical sensing device
GB0711600.7 2007-06-15

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Cited By (3)

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WO2017091508A1 (fr) * 2015-11-24 2017-06-01 The Board Of Trustees Of The University Of Illinois Résonateurs stabilisés par des éléments de micro-réfraction, lasers, et émission laser à plusieurs faisceaux
US10620449B2 (en) 2015-11-24 2020-04-14 The Board Of Trustees Of The University Of Illinois Low-speckle light source and imaging devices with micro-refractive element stabilized laser array
US20200226396A1 (en) * 2019-01-16 2020-07-16 Shenzhen GOODIX Technology Co., Ltd. Anti-spoofing face id sensing using two cameras

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020097401A1 (en) * 2000-08-08 2002-07-25 Luftollah Maleki Optical sensing based on whispering-gallery-mode microcavity
WO2004038370A2 (fr) * 2002-10-22 2004-05-06 Polytechnic University Amelioration de la sensibilite d'un capteur a microspheres
US20040091212A1 (en) * 1999-10-06 2004-05-13 Strecker Brian N. System, probe and methods for colorimetric testing
US6879752B1 (en) * 2002-04-03 2005-04-12 Oewaves, Inc. Film spacer for setting the gap between an optical coupler and a whispering-gallery mode optical resonator
US20050077513A1 (en) * 2003-10-14 2005-04-14 Xudong Fan Hybrid sphere-waveguide resonators
WO2005112042A1 (fr) * 2004-05-12 2005-11-24 The University Court Of The University Of St Andrews Petites pinces optoelectroniques
US20060062508A1 (en) * 2004-09-20 2006-03-23 Chunmei Guo Systems and methods for biosensing and microresonator sensors for same

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040091212A1 (en) * 1999-10-06 2004-05-13 Strecker Brian N. System, probe and methods for colorimetric testing
US20020097401A1 (en) * 2000-08-08 2002-07-25 Luftollah Maleki Optical sensing based on whispering-gallery-mode microcavity
US6879752B1 (en) * 2002-04-03 2005-04-12 Oewaves, Inc. Film spacer for setting the gap between an optical coupler and a whispering-gallery mode optical resonator
WO2004038370A2 (fr) * 2002-10-22 2004-05-06 Polytechnic University Amelioration de la sensibilite d'un capteur a microspheres
US20050077513A1 (en) * 2003-10-14 2005-04-14 Xudong Fan Hybrid sphere-waveguide resonators
WO2005112042A1 (fr) * 2004-05-12 2005-11-24 The University Court Of The University Of St Andrews Petites pinces optoelectroniques
US20060062508A1 (en) * 2004-09-20 2006-03-23 Chunmei Guo Systems and methods for biosensing and microresonator sensors for same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
NOTO M ET AL: "Molecular weight dependence of a whispering gallery mode biosensor", APPLIED PHYSICS LETTERS, AIP, AMERICAN INSTITUTE OF PHYSICS, MELVILLE, NY, vol. 87, no. 22, 23 November 2005 (2005-11-23), pages 223901 - 223901, XP012076695, ISSN: 0003-6951 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017091508A1 (fr) * 2015-11-24 2017-06-01 The Board Of Trustees Of The University Of Illinois Résonateurs stabilisés par des éléments de micro-réfraction, lasers, et émission laser à plusieurs faisceaux
US10620449B2 (en) 2015-11-24 2020-04-14 The Board Of Trustees Of The University Of Illinois Low-speckle light source and imaging devices with micro-refractive element stabilized laser array
US10720747B2 (en) 2015-11-24 2020-07-21 The Board Of Trustees Of The University Of Illinois Micro-refractive element stabilized resonators, lasers and multiple beam lasing
US20200226396A1 (en) * 2019-01-16 2020-07-16 Shenzhen GOODIX Technology Co., Ltd. Anti-spoofing face id sensing using two cameras

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