WO2021048565A1 - Capteur pour détecter un changement d'indice de réfraction - Google Patents

Capteur pour détecter un changement d'indice de réfraction Download PDF

Info

Publication number
WO2021048565A1
WO2021048565A1 PCT/GB2020/052200 GB2020052200W WO2021048565A1 WO 2021048565 A1 WO2021048565 A1 WO 2021048565A1 GB 2020052200 W GB2020052200 W GB 2020052200W WO 2021048565 A1 WO2021048565 A1 WO 2021048565A1
Authority
WO
WIPO (PCT)
Prior art keywords
optical
waveguide
light
optical waveguide
angle
Prior art date
Application number
PCT/GB2020/052200
Other languages
English (en)
Inventor
Nicholas John Goddard
Ruchi Gupta
Original Assignee
Process Instruments (Uk) Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Process Instruments (Uk) Ltd filed Critical Process Instruments (Uk) Ltd
Publication of WO2021048565A1 publication Critical patent/WO2021048565A1/fr

Links

Classifications

    • 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
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length
    • 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
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55—Specular reflectivity
    • G01N21/552—Attenuated total reflection
    • 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
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55—Specular reflectivity
    • 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
    • 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
    • G01N2021/7706—Reagent provision
    • G01N2021/7723—Swelling part, also for adsorption sensor, i.e. without chemical reaction
    • 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
    • G01N2021/7756—Sensor type
    • G01N2021/7763—Sample through flow
    • 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
    • G01N2021/7776—Index
    • 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
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N21/05—Flow-through cuvettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/08—Optical fibres; light guides

Definitions

  • the invention relates to sensors and methods of sensing, such as optical sensors and optical sensing methods.
  • the invention relates to leaky waveguide optical sensors for detecting a substance placed in contact with the sensor, according to changes in the optical properties of the sensor induced by the substance.
  • Optical waveguide sensors provide a mechanism by which light guided within a waveguide, between the internal surface of the waveguide, is able to interact with a substance placed in contact with an external surface of the waveguide.
  • the waveguide is structured in such a way that the evanescent electrical field of the guided light wave is able to penetrate into the external substance through the interface formed between the waveguide and the external substance.
  • the interaction of the penetrating evanescent field with the external substance influences the optical properties (e.g. intensity) of the light guided within the waveguide.
  • measured changes in these optical properties may be found to correlate with changes in properties of the substance.
  • the invention aims to provide an alternative.
  • the invention is an optical sensor based on the direct observation of dip-peak pairs in the light reflected from an optical waveguide, such as a so-called leaky waveguide (LW).
  • LW leaky waveguide
  • This phenomenon is unexpected and is found to be increasingly apparent when the refractive index contrast between the waveguide material and a sample material becomes lower.
  • a refractive index contrast equal to or less than about 0.00500 is preferable, such as a contrast in the range of about 0.00200-0.00500 for example.
  • the waveguide may be illuminated obliquely through a side of the waveguide, with a beam of light configured to inject light into the waveguide covering a range of angles of incidence simultaneously.
  • a convergent beam of light such as a wedge-shaped beam may be used for this purpose.
  • the waveguide is believed to act as a Gires-Tournois optical resonator at particular angles of incidence of the beam of light at which the waveguide resonates to support resonator modes in the waveguide. This is believed to result in a coupling between transverse modes and longitudinal modes of the light beam and the resulting formation of dip-peak pairs for each waveguide mode.
  • the waveguide may provide sensitivity comparable to that of surface plasmon resonance (SPR) optical sensors, but without the requirement for a metallic coating essential for SPR sensors, as described above.
  • the waveguide may comprise a Hydrogel Optical Waveguide (HOW). This may comprise a slab waveguide.
  • the waveguide may be disposed on a solid substrate (e.g. glass), for support.
  • the refractive index of the material of the LW may be intermediate between that of the substrate and the sample.
  • a process other than total internal reflection (TIR) may occur within the waveguide to induce limited confinement of light in at the waveguide making the waveguide leaky, leading to a coupling of light into and out of the waveguide at specific resonance angles of oblique incidence.
  • the invention may provide a sensor for sensing a change in a refractive index caused by the presence of a substance, comprising: an optically transparent substrate (e.g. a surface of a prism); an optical waveguide formed upon a surface of the substrate thereat to form a first optical interface with the surface of the substrate for receiving light therethrough, wherein the optical waveguide comprises an external surface opposing the first optical interface for forming a second optical interface by contact with said substance; a light source configured to inject into the optical waveguide a convergent beam of probe light having a curved optical wavefront such that the probe light is guided along the optical waveguide between the first and second optical interfaces; a detector configured to receive probe light returned from the waveguide via the first optical interface across an interval of oblique angles (concurrently or successively) relative to the first optical interface; wherein the detector is arranged to detect a change in an angle within said interval at which the received probe light achieves a peak or a trough in light intensity,
  • an optically transparent substrate
  • the optical modes and the resonances set up in the waveguide by the injection of the probe light into it are found to be sensitive to the change in refractive index at the second optical interface.
  • This change in refractive index may result from a change in the refractive index of the sample material in contact with the second optical interface externally, and/or may also result from an ingress of sample material into the body of the optical waveguide (which may be porous) so as to change the effective refractive index of the optical waveguide itself at the second optical interface or/and at depths below that interface and within the body of the optical waveguide.
  • the optical waveguide may be configured for use in detecting changes of refractive index caused by the presence of a substance within a fluid, such as a gas or a liquid (e.g. aqueous) solution. This is advantageous also if the waveguide is porous and intended to absorb the fluid into its porous structure as a part of the detection process. It is found that the use of an optical waveguide having a refractive index close to (e.g. greater than) that of the fluid is beneficial in supporting strong dip-peak structures in the angular spectrum of the reflection spectrum of the waveguide as detected by the detector.
  • the optical waveguide may be formed from a material having a refractive index not exceeding 1 .38000 in respect of light having a wavelength of 650nm. More preferably, the optical waveguide may be formed from a material having a refractive index not exceeding 1 .36800 in respect of light having a wavelength of 650nm. For example, the optical waveguide may be formed from a material having a refractive index on the range from 1 .30000 to 1 .36800 in respect of light having a wavelength of 650nm.
  • the optical waveguide is most preferably a leaky waveguide (LW) configured to support leaky optical modes in respect of the injected probe light. Accordingly, by using a LW the out- coupling of light from within the waveguide, at the resonance angles of the waveguide, is made very efficient and improves sensitivity.
  • LW leaky waveguide
  • the optical waveguide is preferably porous.
  • the optical waveguide preferably comprises a porous material adapted to admit diffusion of an aforesaid substance into the optical waveguide via the second optical interface. As discussed above, this is desirable to permit the effective refractive index of the body of the optical waveguide to change in response to the presence of a substance being (to be) detected.
  • the porosity may be configured to admit diffusion of liquids, or gasses, for the purposes of inducing/causing a change in the effective refractive index of the optical waveguide itself.
  • the optical waveguide may comprise a material forming a hydrogel matrix.
  • the optical waveguide may be formed from a hydrogel or a dehydrated hydrogel matrix which is re- hydratable to form a hydrogel.
  • the light source may be arranged to form a convergent beam of probe light which is convergent in all dimensions (e.g. x-direction; y-direction) transverse to the longitudinal/propagation axis (e.g. z-direction) of the beam.
  • the beam may be conically convergent, with a circular or elliptical cross-sectional shape.
  • the light source is preferably arranged to form said convergent beam of probe light as a wedge-shaped beam which is convergent in a first direction (e.g. x-direction) orthogonal to the axis of the beam of probe light (e.g. z-direction of propagation), but which is not convergent (or is less convergent) in a second direction (e.g. y-direction)which is orthogonal to both the first direction and said axis.
  • the beam may be convergent, with a rectangular cross- sectional shape.
  • the direction of non-convergence may preferably be parallel to the surface of the waveguide, and this may promote transverse modes of the beam parallel to the direction of beam convergence and transverse to the surface of the waveguide, for coupling to longitudinal beam modes reflecting back and forth between opposing waveguide surfaces within the waveguide. This may assist in generating Gires-Tournois resonator-like resonances within the waveguide.
  • the optical waveguide may be a planar waveguide in which the first optical interface and the second optical interface are disposed in substantially plane-parallel relative opposition and separated by a substantially uniform waveguide thickness of at least 1 ⁇ m.
  • the waveguide thickness preferably does not exceeding 10 ⁇ m.
  • the detector may be arranged to determine: a first aforesaid angle at which the received probe light achieves a dip or trough in light intensity; a second aforesaid angle at which the received probe light achieves a peak in light intensity; a mean as an average of the first aforesaid angle and the second aforesaid angle; a change in the refractive index at the second optical interface (e.g. of the substance and/or of the waveguide) according to a change in the mean angle.
  • the second angle is preferably greater than the first aforesaid angle.
  • the peak is preferably a maximum (e.g. the greatest value achieved) in the light intensity within the interval of angles.
  • the trough is preferably a minimum (e.g. the lowest value achieved) in the light intensity within the interval of angles.
  • the peak is preferably the first peak that follows an aforesaid trough in angular distance along the interval of angles. For example, the peak may be paired with the dip/trough.
  • the invention may provide a pH sensor comprising a sensor as described above in which the optical waveguide comprises a material forming a hydrogel matrix adapted to swell or shrink thereby to change the refractive index of the optical waveguide in reaction to changes in the pH of said substance at said second optical interface.
  • the invention may provide a chlorine sensor comprising a sensor as described above in which the optical waveguide comprises a material forming a hydrogel matrix containing chlorine-reactive groups adapted to change the refractive index of the optical waveguide in reaction to chlorine at said second optical interface.
  • the invention may provide a biosensor comprising a sensor as described above in which the optical waveguide comprises a material forming a hydrogel matrix adapted to permit the binding thereto of biological analyte materials via said second optical interface.
  • the binding of an analyte to bio-recognition species immobilised in the waveguide changes its refractive index and the angular position of the dip-peak pair, which provides the bio-sensing mechanism.
  • the senor described above implements a corresponding method for sensing a change in a refractive index.
  • the method is not intended to be limited to implementation by a particular apparatus and, for completeness, the corresponding method is detailed below.
  • the invention may provide a method for sensing a change in a refractive index cause by the presence of a substance, comprising: providing an optically transparent substrate bearing an optical waveguide upon a surface of the substrate defining a first optical interface with the surface of the substrate for receiving light therethrough; by contact with said substance, forming a second optical interface at an external surface of the optical waveguide opposing the first optical interface; injecting into the optical waveguide a convergent beam of probe light having a curved optical wavefront such that the probe light is guided along the optical waveguide between the first and second optical interfaces; receiving probe light returned from the waveguide via the first optical interface across an interval of oblique angles (e.g.
  • the method may include forming the convergent beam of probe light as a conical beam of light or as a wedge-shaped beam of light which is convergent in a first direction orthogonal to the axis of the beam of probe light, but which is not convergent in a second direction which is orthogonal to both the first direction and that axis.
  • the method may include the steps, performed by the detector, of determining: a first said angle at which the received probe light achieves a trough in light intensity; a second said angle at which the received probe light achieves a peak in light intensity; a mean angle as an average of the first angle and the second angle; and a change in the refractive index at the second optical interface (e.g. of the substance and/or the optical waveguide) according to a change in said mean angle.
  • the optical waveguide may be formed from a material having a refractive index not exceeding 1 .38000 in respect of light having a wavelength of 650nm. More preferably, the optical waveguide may be formed from a material having a refractive index not exceeding 1 .36800 in respect of light having a wavelength of 650nm. For example, the optical waveguide may be formed from a material having a refractive index on the range from 1 .30000 to 1 .36800 in respect of light having a wavelength of 650nm.
  • the optical waveguide is most preferably a leaky waveguide configured to support leaky optical modes in respect of the injected probe light.
  • the optical waveguide is preferably porous.
  • the optical waveguide preferably comprises a porous material adapted to admit diffusion of an aforesaid substance into the optical waveguide via the second optical interface.
  • the optical waveguide may comprise a material forming a hydrogel matrix.
  • the optical waveguide may be formed from a hydrogel or a dehydrated hydrogel matrix which is re- hydratable to form a hydrogel.
  • the optical waveguide may be a planar waveguide in which the first optical interface and the second optical interface are disposed in substantially plane-parallel relative opposition and separated by a substantially uniform waveguide thickness of at least 1 ⁇ m.
  • the waveguide thickness preferably does not exceeding 10 ⁇ m.
  • the second angle is preferably greater than the first aforesaid angle.
  • the peak is preferably a maximum in the light intensity within the interval of angles.
  • the trough is preferably a minimum in the light intensity within the interval of angles.
  • the peak is preferably the first peak that follows an aforesaid trough in angular distance along the interval of angles.
  • the method may be a method for pH sensing in which the optical waveguide comprises a material forming a hydrogel matrix adapted to swell or shrink thereby to change the refractive index of the optical waveguide in reaction to changes in the pH of said substance at said second optical interface.
  • the method may be a method sensing chorine in which the optical waveguide comprises a material forming a hydrogel matrix containing chlorine-reactive groups adapted change the refractive index of the optical waveguide in reaction to chlorine at said second optical interface.
  • the method may be a method for sensing a biological analyte material in which the optical waveguide comprises a material forming a hydrogel matrix adapted to permit the binding thereto of biological analyte materials via said second optical interface.
  • Figure 1 shows a schematic diagram of a sensor apparatus
  • Figure 2 shows a diagram of a sensor apparatus
  • FIG. 3A shows a schematic diagram of a Gires-Tournois (GT) optical resonator
  • Figure 3B shows a schematic diagram of a reflectivity and an optical phase shift of reflected light from the GT resonator of Figure 3A, as a function of light incidence angle;
  • Figure 3C schematically shows a wedge-shaped optical beam convergent upon a leaky waveguide obliquely
  • Figure 4 shows an optical reflectivity (and phase shift: see inset) angular resonance spectrum of light out-coupled from a leaky waveguide (acting as a GT resonator) according to an example of the invention, together with a schematic angular spectrum indicating the angular distribution of GT resonator modes caused by an optical coupling between longitudinal modes and transverse modes of the probe beam having a curved optical wavefront;
  • Figure 5 shows the calculated optical diffraction spectrum of light out-coupled from a leaky waveguide according to a mathematical model consistent with an example of the invention
  • Figures 6(a) and 6(b) show the calculated optical diffraction spectra of light out-coupled from a leaky waveguide according to a mathematical model consistent with an example of the invention
  • Figure 7 shows a diagram illustrating changes in the detected angular position of an angle at which probe light out-coupled from a leaky waveguide achieves a peak or a trough in light intensity, according to an example of the invention
  • Figure 8 shows a further diagram illustrating changes in the detected angular position of an angle at which probe light out-coupled from a leaky waveguide achieves a peak or a trough in light intensity, according to an example of the invention.
  • FIG. 1 shows a schematic diagram of a sensor apparatus 1 according to an embodiment of the invention.
  • Figure 2 shows an apparatus consistent with the schematic diagram of Figure 1.
  • the sensor apparatus comprises a planar leaky waveguide (LW) 2 formed from a hydrogel strip or slab of uniform thickness supported upon the plane surface of a glass prism 3.
  • the glass prism supported within a prism holder 3A, has a refractive index (at optical wavelengths of light) exceeding that of the LW and provides a substrate forming a first optical interface through which probe light 100 from a light source (items 6 -10) is coupled into the LW.
  • LW planar leaky waveguide
  • a flow cell 4 is disposed at the upper, exposed surface of the LW opposite to the first optical interface and, in conjunction with the exposed surface of the LW, it defines a fluid conduit for directing a flow of a fluid substance from a flow cell fluid inlet 13, across the exposed surface of the LW and to a flow cell outlet 14. Whilst flowing across the exposed surface of the LW in contact with it, the substance forms a second optical interface with the LW.
  • the light source comprises a light emitter 10, such as an LED, which may be monochromatic but need not be, and an optical train (items 6-9) for collecting light emitted by the light emitter, collimating it into a collimated light beam, linearly polarising the light of the collimated light beam, and subsequently shaping the polarised and collimated light beam into a beam shape which converges in only one dimension (orthogonal to the longitudinal beam axis) to define a wedge shaped beam.
  • a light emitter 10 such as an LED, which may be monochromatic but need not be
  • an optical train items 6-9 for collecting light emitted by the light emitter, collimating it into a collimated light beam, linearly polarising the light of the collimated light beam, and subsequently shaping the polarised and collimated light beam into a beam shape which converges in only one dimension (orthogonal to the longitudinal beam axis) to define a wedge shaped beam.
  • the optical train comprises an achromatic lens doublet 9 for collecting and collimating the light emitted by the light emitter, followed by a linear polarising filter 8 disposed to receive the collimated light beam and to transmit the portion thereof which is TE linearly polarised, and a subsequent cylindrical lens 6 and subsequent aperture stop 7, configured to receive the TE polarised beam of collimated light and re-shape it converge into a wedge shape 100 (see Figure 3C) the converged wedge tip of which resides within the LW and extends in a direction coplanarwith the plane of the LW.
  • the wedge angle is ⁇ 14° in air or ⁇ 9° in the prism.
  • the light source is disposed to direct the wedge-shaped light bean in to the LW via an input face of the coupling prism 3 in a direction generally or approximately perpendicular to the input face, and at an input angle (q) coinciding with an angle at which the LW is expected to support leaky waveguide modes for the injected light of the beam.
  • an achromatic doublet lens 12 is optionally mounted on a rotating stage together with a camera 5 and configured to focus the reflected probe light beam 101 (containing dip-peak structures 11) upon the sensor chip of the camera 5. Rotation of the rotation stage permits the doublet lens and camera to be rotated, in unison, to an appropriate angular position to receive the reflected probe light.
  • the camera 5 is mounted upon a linear translation stage permitting translation of the photo-detector of the camera in scanning direction which is transverse to the longitudinal axis of the reflected wedge beam 101 and transverse to the length of the converged wedge tip (see 102; Fig.3C) of which resides within the LW.
  • This permits the dip-peak structures 11 to be positioned upon the camera sensor chip as appropriate.
  • the rotational and linear translation stages, and the achromatic doublet lens 12, may be omitted if desired, as shown in Figure 1 .
  • the wedge-shaped nature of the wedge beam ensures that LW is concurrently illuminated by light possessing a curved and convergent optical wavefront spanning an interval of incidence angles. Reflection and diffraction of light of the wedge-shaped beam occurs and returns a reflected wedge of light 101 (see Figure 3C) through the first optical interface in a direction back into the coupling prism 3 towards the camera 5 disposed and at an output angle corresponding with the angle (q) of incidence of the beam of light, in the plane containing the input angle and the normal to the first optical interface.
  • the area of the photo-sensor chip of the camera is sufficient to capture a cross-section of the output wedge beam containing not only the reflected probe light 100 and the central un-diffracted light, but also concurrently containing higher orders of diffracted light defining peak-dip fringes 11 .
  • a scanning photodetector may be used which is configured to detect the reflected/out-coupled probe light over only a narrow angular range not encompassing the full angular range of a group of resonances, but which is configured to scan across successive angles to cover the entire angular range of the resonances and to detect/record reflectivities at all angles within the range scanned, successively rather than concurrently.
  • Gires-Tournois optical resonator As shown schematically in Figure 3A, these comprise two typically parallel reflecting surfaces: an upper reflector which is partially reflecting (e.g. with reflectivity, r 1 ⁇ 1) and a lower reflector which is highly reflecting (e.g. with reflectivity r 2 »1 ) and is separated by a uniform distance (d) from the upper reflector.
  • d is a phase given by the geometry of the resonator:
  • the reflected intensity spectrum of the GT etalon, as well as the phase spectrum, is qualitatively very similar to the reflectivity spectrum observed in the present invention when illuminated by a collimated mechanical scan. Both show intensity ‘dips’ at certain resonance angles of incidence.
  • the reflectivity dips observed when mechanically scanning, in angle of incidence, a collimated (i.e. non-converging) probe light beam across the waveguide of the invention is dominated by scattering losses of light within the waveguide (e.g. porous in structure and prone to some internal light scattering) due to a greater proportion of the light being partially confined within the waveguide for longer (i.e. longer optical path length within the waveguide) when GT resonances occur at GT resonance angles.
  • the Gaussian representation of a light beam forms a complete basis set which can be used to accurately represent many other beam wave functions: i.e. by representing the beam wave function as a weighted sum of Gaussian beams.
  • H x is a Hermite polynomial of order x
  • w(z) represents the radius of the waist of the light beam at a given point, z, along the axis of propagation.
  • the quantity w 0 is the radius of the focal spot of the beam
  • R(z ) is the curvature of the wavefront of light at an axial position z along the z-axis of propagation of the beam. It is noted that the curvature is negative when z ⁇ 0 (i.e. to the ‘left’ of the focus), is infinite at the focus (i.e. becomes planar at that point) and is positive when z>0 (i.e. to the ‘right’ of the focus).
  • h is interpreted as a phase difference between the Gaussian beam and a plane wave of the same wavelength also travelling in the +z direction.
  • the transverse variation, in the x-dimension and the y-dimension, of the electric field of the light beam is therefore Gaussian in profile and of the form: this being in the x-dimension, and: this being in the y-dimension.
  • a phase factor is created by the presence of a curvature, R(z), of the wavefront:
  • N is an integer. This gives, for a given fixed value of N:
  • the value of k satisfies this resonance condition, and represents a longitudinal resonance mode.
  • the values of the transverse mode indices, l and m, within this equation may individually vary without changing the value of l + m).
  • the resonant values of the wave vector k depend on the sum l + m and not on the values of the mode indices, l and m, individually, meaning that for a given longitudinal resonator mode (i.e. a given value of N), there exist additional degenerate transverse modes with mode indices, Z and m, constrained such that the sum is fixed.
  • the resonance condition for a given value of the wave vector k satisfying the longitudinal resonance mode condition in the resonator can be simultaneously satisfied by coupling light (i.e. diffracting within the beam) into to multiple corresponding transverse modes with mode indices, l and m, at different corresponding angles of incidence of the converging light rays forming the beam.
  • transverse modes ( l + m ) are absent from the light beam, such as if there is no curvature in the wavefronts of the beam, e.g. caused by focussing, then these additional resonances will be absent from the resonator resonance pattern: only longitudinal resonance modes will be present.
  • the act of forming a convergent optical beam creates transverse modes within the beam and allows these pre-existing transverse modes to couple to longitudinal modes in the resonator cavity thereby to permit additional resonance modes within the resonator cavity, when the light beam is injected into it.
  • the transverse modes of the beam are associated with variations in the electrical field of the beam along axes (x, y) transverse to the propagation axis (z), and one of these axes may correspond to a direction extending across (e.g. plane parallel) to the plane of the reflecting surfaces of the optical resonator.
  • an extended focal region e.g. a wedge beam
  • Figure 4 shows the output of the LW of the embodiment of the invention when illuminated through a prism with a converging wedge beam (i.e. a range of angles of incidence simultaneously) produced by a cylindrical lens.
  • the dip-peak resonance structure created in the reflected (out-coupled) probe light beam is imaged by a camera, and an image of the result is provided in Figure 4 inset (i) along with the corresponding intensity profile as a function of varying probe beam angle of incidence (and angle of reflection, by symmetry).
  • the intensity profile of the same LW when illuminated with a mechanically scanned collimated beam and recorded by a photodiode is also shown in Figure 4.
  • the depth/ height of the dip/ peak decreased as the order of the LW mode increased because the zero-order optical mode is better confined in the waveguide than the second-order mode.
  • the resonance angle corresponding to the zero-order mode is greater than the higher-order modes.
  • the Fresnel reflectivity at the substrate/waveguide interface increases at high angles, thus increasing the Q factor and in turn leading to improved confinement of the zero-order mode in the waveguide.
  • FIG. 4 shows that the reflectivity 40 of the LW across a range of angles of incidence of light from the probe light beam 100, encompassing several of the mode resonances imaged simultaneously by the camera 5 of the apparatus.
  • the reflectivity 41 produced by replacing the wedge-shaped beam 100 with a collimated (i.e. non-converging) probe light beam which was simply mechanically scanned through the same range of angles of incidence. It can be immediately seen that when a wedge-shaped optical probe light beam is used, this generates strong resonance structures in the reflectivity spectrum on the form of a zero-order, then first-order, and then second-order optical resonances showing multiple dip- peak pairs 40 at successive angular (incidence) positions.
  • the reflection and transmission coefficients can be generated from the system matrix. Fresnel's approximation was then used to propagate the outgoing optical field to the detector. MATLAB was used to obtain the shifted FFT of the amplitude transmittance coefficient, which was multiplied with Equation 1 .
  • Equation 1 k: wave vector z: distance to the detector (m), l: wavelength (m), u 2 : quadratic phase term.
  • Equation 1 Equation 1 .
  • the thickness of the slab waveguides was such that only the zero-order mode was supported.
  • the wavelength was 650 nm and the propagation distance was 5 cm.
  • the dip-peak was only visible when the phase change was very sharp (5 - 95% change over 0.175°), and not visible when the phase change was broader (5 - 95% change over 1.505°). This shows that only very narrow waveguide resonances are visible by this method, which in turn requires a very low index waveguide.
  • Figure 6(a) shows that the same effect occurs in single- and two-moded waveguides. This implies that this phenomenon can be observed in thick waveguides of low refractive index, but as the film increases in thickness, the higher order modes become progressively weaker.
  • Curve 61 corresponds to a film thickness of 2 microns
  • curve 62 corresponds to a film thickness of 4 microns.
  • Figure 6(b) shows the evolution of the reflectivity changes with increasing propagation distance.
  • Curves 63, 64, 63 and 66 correspond, respectively, to propagation distances of 5cm, 10cm, 20cm and 40cm. It can be seen that the peak-to-peak intensity change increases with the propagation distance.
  • a LW was fabricated by spin coating 6% (w:v) solutions of poly(acrylamide) (poly(AAm)) at 4000 rpm and crosslinked via glutaraldehyde (GA).
  • Blocks of poly(AAm) and copolymers are commonly prepared by three-dimensional radical polymerisation of monomers and a crosslinker, bis-acrylamide.
  • the approach is, however, not well-suited to fabricate these thin films by spin coating because (1) the low viscosity monomer/ crosslinker solutions fly off without coating the substrate, (2) reducing oxygen inhibition of radical polymerisation in thin films is challenging, and (3) the hazardous nature of acrylamide/ bis-acrylamide.
  • Decon 90 Glycerol (M w : 92) and N- (3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) were purchased from Fisher (Loughborough, UK). Streptavidin (N7021S, contained 140 mM, 10 mM KCI, NaCI, 8 mM sodium phosphate and 2 mM potassium phosphate) and N-Hydroxysulfosuccinimide sodium salt (sulfo-NHS) were supplied by New England Biolabs (Hertfordshire, UK) and Cambridge Biosciences (Cambridge, UK) respectively.
  • EDC N- (3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride
  • the poly(AAm-AA) film was activated in-situ by reacting the carboxylic acid groups with 1.8 mg of EDC and 2 mg of sulfo-NHS dissolved in 100 mM HEPES, pH 5.8 buffer re-circulated through the flowcell for ⁇ 1 h.
  • the film was washed with HEPES buffers of pH 5.8 and then pH 7.4.
  • the remaining solutions were prepared in 100 mM HEPES, pH 7.4. ⁇ 0.2 mg/ ml of streptavidin and BSA solutions were pumped through one channel each of the flowcell to react the amine groups in the proteins with the EDC-sulfo NHS activated poly(AAm-AA) film.
  • the regions of the waveguide positioned under the flow channels through which streptavidin and BSA solutions were pumped provided the measurement and reference signals respectively. ⁇ 67.5 nM biotin Anti-lgG and ⁇ 133.3 nM IgG solutions were pumped through both the flow channels sequentially. A buffer wash was performed in between the protein solutions and resonance angle was monitored as different solutions were introduced on the waveguide.
  • a BK7 equilateral prism 3 (Qioptic Photonics, Denbighshire, UK) was used to couple light in and out of the hydrogel waveguide 2.
  • the light emitter LED 10 (TL-6, iC-Haus, Bodenheim, Germany) and 6.6 Mpixel CMOS camera 5 (PL-B781 , Pixelink, Ottowa, Canada) were mounted on rails connected to goniometers to allow radial and angular freedom respectively.
  • the output of the LED 10 was collimated, TE-polarised and then passed through a 40 mm focal length cylindrical lens 6 and an aperture 7 to form a wedge beam 100 to probe the hydrogel waveguide with a range of angles of incidence simultaneously.
  • the camera allowed a 7.7 mm wide section of the LW to be imaged, which allowed both the flow channels to be captured in a single frame.
  • the collimated mechanical scan (trace 41 in Figure 4) was obtained using a TE-polarised laser as the light source (Acculase, RS Components, Northamptonshire, UK) with a peak wavelength of 650 nm and a power of 5 mW and photodiode (OSD100-6, Centronic, Surrey, UK).
  • the LED light source and lens train (items 6-10 of Fig.1) were not used in that case.
  • Fluids were pumped through the flow cell 4 using a peristaltic pump (Minipuls® 3, Gilson, Bedfordshire, UK) at a flow rate of 0.2 ml min 1 .
  • the flowcell 4 was CNC machined from 3 mm thick black PMMA forming two recessed cavities to obtain 2 mm wide and 0.2 mm deep channels surrounded by grooves 1 mm wide and 0.75 mm deep in which O-rings were mounted.
  • the flow cell 4 was placed on the waveguide 2 and held in place using a water-cooled fixture maintained at 20 °C.
  • the intensity of the dip and peak did not change significantly as the glycerol concentration changed, because the refractive index contrast between the waveguide and sample remained substantially constant.
  • the slope of the calibration plot of the angular positions of the dip and peak of the dip-peak pair versus refractive index of different concentrations of glycerol solutions provided the RIS of the LW for glycerol.
  • the RIS of the LW with poly(AAm) waveguide to glycerol was 119.58 ⁇ 0.37 and 119.42 ⁇ 0.63 ° Rill -1 at the 95% confidence level for channels 1 and 2 respectively.
  • the RIS is a key figure of merit for comparing the performance of label-free optical biosensors.
  • the RIS of the LW to glycerol is comparable to SPR on gold, which has a RIS between 95 and 204° RIU -1 depending on the prism index and configuration.
  • the gold film is typically deposited on a high refractive index substrate such as SF10, which is several times more expensive than the soda-lime glass substrate used to fabricate the LWs reported in this work (soda-lime microscope slides of dimensions 25 mm by 75 mm).
  • Well-controlled and high quality gold films required for SPR are deposited using vacuum evaporators.
  • the poly(AAm) waveguides in the LWs were deposited via spin coating.
  • the waveguide should be porous enough to allow these to diffuse in.
  • the porosity was determined by using PEG solutions of similar refractive index but different molecular masses, This showed that the shift in resonance angle corresponding to 1% (w:v) PEGs of M w 10 kD, 100 kD and 300 kD solutions is ⁇ 41%, ⁇ 29% and ⁇ 21% of the value observed for glycerol solution of similar refractive index (curve 71 of Figure 7).
  • FIG. 7 shows that the variation in the response of the LW for different glycerol and PEG solutions across both 2 mm wide flow channels was ⁇ 1.55%. Minimal variations in the area-to-area response is required so that the shift in the resonance angle because of common-mode effects (e.g. temperature, composition of sample matrix) and analyte-ligand interactions can be de-convoluted using spatially separated sensor and reference regions of the sensor.
  • the hydrogel waveguide layer is porous to allow the analyte(s) (e.g. hydrogen ions or chlorine) to diffuse into the waveguide.
  • Multi-analyte sensing may be carried out by spatially patterning the sensing molecules over the surface of the sensor.
  • the wedge beam may provide spatial resolution to allow different areas of the chip to be monitored.
  • Real-time monitoring of analyte binding can be carried out, e.g. for the antibody-antigen binding.
  • a suitable non-ionisable cross-linked polymer backbone may be used to form a hydrogel matrix of the waveguide.
  • An example is polyacrylamide.
  • This material may be postpolymerisation modified with pendant ionisable groups (such as amines or carboxylic acids) that cause the polymer to swell/shrink as the pH changes and the ionisable groups change their charge.
  • amines will be protonated at pH below their pKa, and the positive charges on the protonated amines will cause the polymer to swell at pH below the pKa.
  • the hydrogel waveguide may incorporate monomers with ionisable groups in the cross-linked polymer backbone used to form a hydrogel matrix of the waveguide , thereby to form an ionisable copolymer.
  • examples include acrylamide-acrylic acid copolymers.
  • the hydrogel waveguide matrix may comprise a suitable non-reactive cross-linked polymer backbone which has attached to it reversible chlorine-reactive groups.
  • An example is cyanuric acid, where chlorine can reversibly displace hydrogen atoms on the triazine nitrogens, attached to the polymer through one of the nitrogen atoms in the triazine ring.
  • Biosensing may be performed this using antibody-antigen binding at the matrix of the hydrogel waveguide.
  • this method may be applied to any sensing mechanism that involves a change in refractive index. Examples include aptamers, DNA, enzymes, receptors.
  • bio-sensing is demonstrated herein using LWs made of poly(AAm-AA) because it provides functional groups that allowed covalent attachment of analyte-specific moieties (e.g. antibodies) to the hydrogel waveguide.
  • 3% (w:v) polymer solution containing 250 ppm GA was spin coated at 2000 rpm. The films were allowed to crosslink overnight following which, the carboxylic acid groups in the regions of the waveguide positioned under the sensor and reference flow channels were activated with EDC-sulfo NHS to allow covalent attachment of streptavidin and BSA respectively. Subsequently, the same solutions were pumped through both sensor and reference channels, and their corresponding response to each solution was recorded.
  • Figure 8(a) shows absolute shifts in the resonance angle of the sensor and reference regions.
  • Figure 8(b) provides the differential response (curve 86), which was obtained by subtracting the average response of the reference from the sensor region.
  • figure 8 shows a further diagram illustrating changes in the detected angular position of an angle at which probe light out-coupled from a leaky waveguide achieves a peak or a trough in light intensity, according to an example of the invention.
  • the results for three different samples (curves 80, 81 and 82) are compared to the results for three different reference channels (curves 83, 84 and 85).
  • the effective index of the waveguide layer changes, the angular position of this dip- peak pair changes, allowing binding events to be monitored in real-time. Relying solely on diffraction to visualize the waveguide resonances has resulted in a very simple optical biosensor, consisting of a glass slide with polyacrylamide and copolymers waveguide layer.
  • the LW has a refractive index sensitivity of ⁇ 119.5 ° Rill -1 , which is comparable to the current market-leading technology, surface plasmon resonance (SPR).
  • SPR surface plasmon resonance
  • the minimum detectable change in refractive index of the LW was 4.5 x 10 -6 RIU.
  • Biosensing was demonstrated using a poly(AAm-AA) waveguide by activating the carboxylic acid groups with EDC/NHS to allow covalent immobilisation of streptavidin, followed by non-covalent binding of biotin Anti-lgG and then IgG.
  • This invention advances the field of label-free optical sensors because the reported LW may be fabricated using scalable manufacturing processes, is made of widely available low cost materials, requires affordable instrumentation, and has comparable performance to SPR. This in turn makes the LW biosensor highly attractive for applications such as point-of-care (PoC) diagnostics, or for pH or Chlorine sensing.
  • PoC point-of-care
  • the waveguide may simply be a thin (1 - 5 microns) porous hydrogel film 2 on a glass or plastic substrate 2A (e.g. Fig.3A).
  • the glass or plastic substrate may be are coupled to a prism 3 using index matching fluid or gel (not shown), while polymer substrates can have the prism moulded in to avoid using index matching fluids or gels.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Plasma & Fusion (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

Selon un premier aspect, l'invention concerne un capteur pour détecter un changement d'indice de réfraction provoqué par la présence d'une substance, comprenant : un substrat optiquement transparent (par exemple une surface d'un prisme); un guide d'ondes optique formé sur une surface du substrat au niveau de celui-ci pour former une première interface optique avec la surface du substrat pour recevoir de la lumière à travers celui-ci, le guide d'ondes optique comprenant une surface externe opposée à la première interface optique pour former une seconde interface optique par contact avec ladite substance; une source de lumière configurée pour injecter dans le guide d'ondes optique un faisceau convergent de lumière de sonde ayant un front d'onde optique incurvé de telle sorte que la lumière de sonde est guidée le long du guide d'ondes optique entre les première et seconde interfaces optiques; un détecteur configuré pour recevoir une lumière de sonde renvoyée par le guide d'ondes par l'intermédiaire de la première interface optique sur un intervalle d'angles obliques (simultanément ou successivement) par rapport à la première interface optique; le détecteur étant conçu pour détecter un changement d'un angle à l'intérieur dudit intervalle auquel la lumière de sonde reçue atteint un pic ou un creux dans l'intensité de la lumière, et pour déterminer un changement de l'indice de réfraction au niveau de la seconde interface optique provoquée par la présence de la substance en fonction du changement dudit angle.
PCT/GB2020/052200 2019-09-13 2020-09-11 Capteur pour détecter un changement d'indice de réfraction WO2021048565A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB1913288.5A GB2587024A (en) 2019-09-13 2019-09-13 A sensor
GB1913288.5 2019-09-13

Publications (1)

Publication Number Publication Date
WO2021048565A1 true WO2021048565A1 (fr) 2021-03-18

Family

ID=68315188

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2020/052200 WO2021048565A1 (fr) 2019-09-13 2020-09-11 Capteur pour détecter un changement d'indice de réfraction

Country Status (2)

Country Link
GB (1) GB2587024A (fr)
WO (1) WO2021048565A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021207834A1 (fr) * 2020-04-13 2021-10-21 The University Of British Columbia Capteur photonique utilisant un laser à longueur d'onde fixe

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5434663A (en) * 1990-08-17 1995-07-18 Fisons Plc Analytical device
WO1999044042A2 (fr) * 1998-02-24 1999-09-02 The University Of Manchester Institute Of Science & Technology Structures de guide d'onde
EP2499492A1 (fr) * 2009-11-11 2012-09-19 EMD Millipore Corporation Capteur optique
US8920729B2 (en) * 2008-10-17 2014-12-30 Vanderbilt University Porous membrane waveguide sensors and sensing systems therefrom for detecting biological or chemical targets

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4033912C2 (de) * 1990-10-25 1995-05-24 Fraunhofer Ges Forschung Optischer Sensor

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5434663A (en) * 1990-08-17 1995-07-18 Fisons Plc Analytical device
WO1999044042A2 (fr) * 1998-02-24 1999-09-02 The University Of Manchester Institute Of Science & Technology Structures de guide d'onde
US8920729B2 (en) * 2008-10-17 2014-12-30 Vanderbilt University Porous membrane waveguide sensors and sensing systems therefrom for detecting biological or chemical targets
EP2499492A1 (fr) * 2009-11-11 2012-09-19 EMD Millipore Corporation Capteur optique

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021207834A1 (fr) * 2020-04-13 2021-10-21 The University Of British Columbia Capteur photonique utilisant un laser à longueur d'onde fixe
US11940386B2 (en) 2020-04-13 2024-03-26 The University Of British Columbia Photonic sensor using a fixed-wavelength laser

Also Published As

Publication number Publication date
GB201913288D0 (en) 2019-10-30
GB2587024A (en) 2021-03-17

Similar Documents

Publication Publication Date Title
US5846843A (en) Sensor using long range surface plasmon resonance with diffraction double-grating
US5864641A (en) Optical fiber long period sensor having a reactive coating
US6870627B2 (en) System for directed molecular interaction in surface plasmon resonance analysis
JPWO2005078415A1 (ja) 表面プラズモン共鳴センサー
US20020003627A1 (en) Doubly-differential interferometer and method for evanescent wave surface detection
US20100195106A1 (en) Detecting element, and target substance detecting device and method of detecting target substance using the same
US11448580B2 (en) Biodetector based on interference effect of thin film with ordered porous nanostructures and method for using same to detect biomolecules
US7517656B2 (en) Optical sensor and methods for measuring molecular binding interactions
JPH11512186A (ja) 表面構造変化の決定のための光センサの屈折率の監視
Goddard et al. Real-time biomolecular interaction analysis using the resonant mirror sensor
US20230194425A1 (en) Optical sensor of bio-molecules using interferometer
CN108709874A (zh) 基于自混合干涉的表面等离子体共振传感装置及方法
Fattinger Focal molography: coherent microscopic detection of biomolecular interaction
Goddard et al. A novel manifestation at optical leaky waveguide modes for sensing applications
WO2021048565A1 (fr) Capteur pour détecter un changement d'indice de réfraction
CN107356560B (zh) 全反射式斜入射光反射差扫描成像装置及其使用方法
FR2935804A1 (fr) Procede de recherche d'au moins un analyte dans un milieu susceptible de le contenir
Schasfoort History and Physics of Surface Plasmon Resonance
Wiki et al. Compact integrated optical sensor system
US20190056389A1 (en) System and method for determining the presence or absence of adsorbed biomolecules or biomolecular structures on a surface
US8367399B2 (en) Method for measuring molecular interactions by measurement of light reflected by planar surfaces
Werneck et al. POF biosensors based on refractive index and immunocapture effect
KR100588987B1 (ko) 표면 플라즈몬 공명현상을 이용한 광학적 분석장치 및 그 분석방법
Duveneck et al. Novel generation of luminescence-based biosensors: single-mode planar waveguide sensors
Dahne et al. Detection of antibody-antigen reactions at a glass-liquid interface: A novel fibre-optic sensor concept

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20772402

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20772402

Country of ref document: EP

Kind code of ref document: A1