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WO2010064058A1 - Dispositif de détection - Google Patents

Dispositif de détection Download PDF

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Publication number
WO2010064058A1
WO2010064058A1 PCT/HU2009/000098 HU2009000098W WO2010064058A1 WO 2010064058 A1 WO2010064058 A1 WO 2010064058A1 HU 2009000098 W HU2009000098 W HU 2009000098W WO 2010064058 A1 WO2010064058 A1 WO 2010064058A1
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WO
WIPO (PCT)
Prior art keywords
sensor device
sample
container
arm
output signal
Prior art date
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Ceased
Application number
PCT/HU2009/000098
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English (en)
Inventor
András DÉR
Elmar Klaus Wolf
Pál ORMOS
Sándor VALKAI
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BIOLOGICAL RESEARCH CENTER OF HUNGARIAN ACADEMY OF SCIENCE
Original Assignee
BIOLOGICAL RESEARCH CENTER OF HUNGARIAN ACADEMY OF SCIENCE
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Publication of WO2010064058A1 publication Critical patent/WO2010064058A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • G01N21/75—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
    • G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00—Measuring instruments characterised by the use of optical techniques
    • G01B9/02—Interferometers
    • G01B9/02049—Interferometers characterised by particular mechanical design details
    • G01B9/02051—Integrated design, e.g. on-chip or monolithic
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00—Measuring instruments characterised by the use of optical techniques
    • G01B9/02—Interferometers
    • G01B9/02055—Reduction or prevention of errors; Testing; Calibration
    • G01B9/0207—Error reduction by correction of the measurement signal based on independently determined error sources, e.g. using a reference interferometer
    • G01B9/02072—Error reduction by correction of the measurement signal based on independently determined error sources, e.g. using a reference interferometer by calibration or testing of interferometer
    • 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
    • G01N21/45—Refractivity; Phase-affecting properties, e.g. optical path length using interferometric methods; using Schlieren methods
    • 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
    • G01N21/45—Refractivity; Phase-affecting properties, e.g. optical path length using interferometric methods; using Schlieren methods
    • G01N2021/458—Refractivity; Phase-affecting properties, e.g. optical path length using interferometric methods; using Schlieren methods using interferential sensor, e.g. sensor fibre, possibly on optical waveguide
    • 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
    • G01N2021/7779—Measurement method of reaction-produced change in sensor interferometric

Definitions

  • the invention relates to an integrated optical or fibre optical interferometer based sensor device
  • the invention also relates to uses of said device and methods for adjusting the output signal of said device
  • the idea behind the method is the proper preadjustment of the phase shift of the light propagating in the reference branch of the MZ interferometer This can be realized by changing the refi active index of an ad-layer deposited on top of the reference blanch of the interferometer via an external control signal According to the physical nature of the control signal, one can distinguish a photo-optical and an electi o-optical solution
  • the invention provides for the following embodiments ⁇ n integrated optical or fibre optical interferometer based sensor device, said device comprising
  • an optical waveguide comprising a light path, said light path comprising a lead-in portion, a first junction with an input and at least two outputs, said input being connected to said lead-in portion, 5 a lead-out portion, a second junction with at least two inputs and an output, said output being connected to said lead-out portion at least a first arm and a second arm, each arm extending between one output of said first junction and one input of said second junction, 0 said first junction being capable of splitting a light beam, that is coupled into said lead-in portion, into at least first and second light beams propagating in said first and second arms, respectively, and said second junction being capable of recombining said first and second light beams and thereby creating an interference pat- ternthereof resulting in an output signal,
  • At least one container for receiving a sample, said at least one container being directly or indirectly at- 5 tached to a first portion of at least one of the arms in such a way that any change taking place within said sample present in said at least one container affects a wave propagation property of said light beam propagating (travelling) in the at least one arm of said optical waveguide to which said at least one container is attached,
  • said adjuster member having an ad-layer of non-linear optical property, an optical property of said ad-layer which being susceptible of a change upon exposition to an external effect, 0 said ad-layer being in contact with a second portion ot at least one of said first and second arms, wherein said first and said second portions of any of the arms are interchangeable and are spatially separated from each other
  • wave propagation property is meant to include any property of the propagating light which can be detected or described by a mathematical equation, preferably it includes at least the wavelength, frequency, 5 intensity, phase and any combination thereof of the propagating light
  • light is understood herein as an electromagnetic radiation in the infrared, visible or ultraviolet range, i e an infrared, visible or ultraviolet light
  • An integrated optical intei ferometer based sensor device comprising at least the following paits 0 - an optical waveguide arrangement comprising a lead-in portion, a first Y junction, a first and a second arm, a second Y junction and a lead-out poi tion, wherein it a propagating light beam is inti oduced into the lead- in portion, it can be split at the first Y junction into a first light beam and a second light beam propagating in the first arm and in the second ai m, respectively, and i ecombine at the second junction resulting in an interference pattern and in turn an output signal, i b - at least one photooptical oi ele ⁇ rooptical adjuster member said adjuster member comprising an ad- layer comprising a non-linear optical matenal whei ein an optical property of the ad-layei can be changed by an external effect, preferably said ad-layer comprising a photooptical material capable of changing
  • At least one container for receiving a sample, said at least one container being dii ectly or indirectly attached to a first portion of either the first or the second arm in an arrangement whei em an alteration of the sample can effect the wave propagation property, e g phase and/or wavelength of the propagating light beam in said first or second arm
  • the sensor device accoi ding to claim 1 wherein said sensor device comprises
  • the sensor device accoi ding to the invention which comprises a) a single adjuster member having an ad-layer being in contact with the second portion of the first arm or the second portion of the second arm, whereas said portions are interchangeable, b) - a first adjuster member having an ad-layer being in contact with the second portion of the first arm, and
  • said adjuster member comprises an ad-layer an optical property of which being susceptible of a change upon exposition to an electromagnetic radiation as an ex- ternal effect, preferably to light, preferably to a lasei light
  • ad-layer comprises a material of non-linear optical property selected from the following group photochromic proteins, polymers of non-linear optical property
  • the photochromic protein is a protein comprising cis retinal, preferably a rhodopson protein, more prefei ably bactei iorhodopsin
  • the conti ol light is a light of a wavelength which is suitable to change the moleculai state of bactei ioi hodopsm
  • said adjuster member comprises an ad-layer an optical property of which being susceptible of a change upon exposition to an electric field
  • the optical property of the ad-layer is susceptible of a change upon exposition to an electromagnetic radiation
  • it is not susceptible of a change upon exposition to an electric field
  • a sensor device of the invention for detecting a change in a sample comprised in said first container, wherein prior to and/or after the change in the sample the at least one adjuster member of said sensor device is exposed to a controlled external effect thereby an optical property of said ad-layei in said adjuster member is changed and in turn a wave propagation property of said light beam propagating in said at least one arm is affected, and thereby the output signal is effected, wherein the controlled external effect is set in such a way that the output signal has a predetermined value
  • a method for adjusting an output signal of a sensor device for detecting a change in a biological sample
  • a method for adjusting an output signal of a sensor device comprising the steps of i) providing a sensor device according to the invention, ii) exposing said at least one adjuster member of said sensor device to a controlled external effect thereby changing an optical property of said ad-layer in said adjuster member and in turn affecting a wave propagation property of said light beam propagating in said at least one arm, in) detecting a change in the interference created by the recombined fu st and second light beams and thereby iv) affecting the output signal, whei ein the conti oiled external effect is set in such a way that the output signal has a predetermined value
  • the method of the invention wherein the controlled external effect is set in such a way that the output signal is essentially constant
  • a transmission function of the output signal is measured or defined as a function of the controlled external signal and the output signal is set to a value wherein the value of the slope (the first derivative of) of the transmission function is at least 70%, at least 80%, at least 90 %, at least 95% of the maximum value of said slope or prefei ably is essentially the of the maximum value of said slope
  • a method for detecting a change in a sample by a sensor device according to the invention comprising the steps of - adjusting the output signal of a sensor device according to the invention
  • said sensoi device comprises - a first container for l eceiving a first sample, said first container being directly or indirectly attached to the first poition of the first ai m, and - a second container for receiving a second sample, said second container being directly or indirectly attached to the first portion of the second arm, and the change in said sample is effected or allowed to occur in the first sample whereas the second sample is unchanged and is considered as a reference sample.
  • the first container is a measuring cuvette and the second container is reference cuvette and the at least one adjuster member is on the first portion of the said second arm of the ligh path in said sensor device.
  • said ad-layer comprises a material of non-linear optical property selected from the following group: photochromic proteins, polymers of non-linear optical property.
  • the photochromic protein is a protein comprising cis retinal, preferably a rhodopson protein, more preferably bacteriorhodopsin.
  • Figure 1 a Scheme of an integrated optical Mach-Zehnder interferometer
  • Figure Ib A schematic representation of an example for a sensor device according to an embodiment of the invention comprising a measuring cuvette and a reference cuvette and a single adjuster member the ad- layer of which comprises a bacteriorhodopsin film.
  • Figure 2. Sinusoidal modulation of the transmitted red light as a function of exciting light intensity.
  • Figure 3 Probe signals measured at the minimum (a), the maximum (b), and the highest slope (c) of the transmission function.
  • Figure 4. Photograph of a sensor chip. Red light of a diode laser was coupled in and out from and to single mode optical fibers. The length of the MZ structure itself was 5mm.
  • Figure 5. Light intensity change of the biosensor due to binding of biotinated mouse antibodies added at the time point of 65s.
  • the basic element of the method is an integrated of fibre optical device, which comprises an interferometer, e.g. a Mach-Zehnder interferometer (Fig. Ia).
  • the interferometer which is utilized in the present sensor is an integrated optical device.
  • MZ Mach-Zehnder
  • the sensor device according to the invention is an integrated optical interferometer based sensor device shown on Figure I b, said device comprising an optical waveguide arrangement comprising a light path, said light path comprising a lead-in portion 1 , a first Y junction 3 with an input and at least two outputs, said input being connected to said lead-in portion
  • a lead-out poition 2 a second Y junction 4 with at least two inputs and an output, said output being connected to said lead-out portion 2 a first arm 5 and a second arm 6, each arm extending between one output of said first Y junction 3 and one input of said second Y junction 4, said first Y junction being capable of splitting a light beam, that is coupled into said lead-in portion I , into at least first and second light beams propagating in said first arm 5 and second arm 6, respectively, and said second Y junction 4 being capable of recombining said fu st and second light beams and thereby creating an lnter- ference pattern thereof i esulting in an output signal 12,
  • said adjuster member having an ad-layer 10 of non-linear optical property, said optical property, preferably refractive index, being susceptible of a change upon exposition to an electromagnetic radiation, preferably to light, and said ad-layer 10 being in contact with a second poi tion of at least one of said first and second arms (52 or 62), - a first container 7 and a second container 8, each one for receiving a sample, said first container 7 being directly or indirectly attached to a first portion of the first arm 5 1 and said second container 8 being directly or indirectly attached to the first portion of the second arm 61 in such a way that any change taking place within said sample present in any of the containers affects a wave propagation property of said light beam propagating in the respective arm of said optical waveguide to which container is attached, wherein said first and said second portions of any of the arms are spatially separated from each other and are interchangeable
  • said sensor device comprises - a first container for l eceiving a first sample, said first container being directly or indii ectly attached to the first portion of the first ai m, and
  • a second container for receiving a second sample, said second container being directly or indirectly attached to the first portion of the second ai m, and the change in said sample is effected or allowed to occur in the first sample whereas the second sample is unchanged and is considered as a reference sample
  • a calibration curve in advance and calculate the extent of the external effect, e g an illuminating controlling light or controlling electric field to achieve a desn ed change in the output signal, e g the output light intensity, i e the value of the transmission function
  • a drift in the output signal is compensated thereby
  • Automation of the woi king point adjustment can be achieved by e g using a control automatic system, which at first changes the intensity of the controlled external effect, e g control signal, e g the control light (e g laser) in a wide range and measures the output signal, e g output light intensity or the derivative (slope) thereot Then the automatic system sets the output signal value between the two extremes (where the derivative is 0, i e the maximum and the minimum) by setting the control led external effect, e g conti ol signal, e g the control light as necerney
  • a control automatic system which at first changes the intensity of the controlled external effect, e g control signal, e g the control light (e g laser) in a wide range and measures the output signal, e g output light intensity or the derivative (slope) thereot Then the automatic system sets the output signal value between the two extremes (where the derivative is 0, i e the maximum and the minimum) by setting the control led external effect, e
  • the device is small for this reason and for sake of portability It can be connected to other integrated optical devices or integrated into microfluidical devices Expenmental examples
  • the photo-optical solution would allow the realization of an all-optical device
  • the basis of operation is that upon light excitation of the ad-layer (which should consist of a non-linear optical material), its refractive index changes that gives rise to a phase shift of the guided light
  • the ad-layer was a made of a photochromic protein, bacte ⁇ orhodopsin, having unique non-linear optical properties [3]
  • a MZ interferometer was pi epared by a photopolyme ⁇ zation technique we formerly adapted for the prepai ation of micromachines and integrated optical structures [4, 5]
  • a thin (ca, 10 urn) film of bacteriorhodopsin was deposited on the top of the reference waveguide branch by layering [5]
  • the light of a diode laser (633 nm, 10 mW) was coupled into a single-mode optical waveguide whose other end was matched to the input of the MZ interferometei by a cr opositionei , and its optimal position was fixed by a transparent glue
  • Another light beam was directed to the bacteriorhodopsin film, so as to control light-induced l etractive index change in the ad-layer
  • the measurement of the transfer characteristics of the interferometer was done under a microscope Without exposure, the optical environment and the effective refractive index was the same in each arm When illuminating, only one of the covered arms was exposed, therefore only thei e was a variation in the index of refraction leading to a phase unbalance in the two arms, and interference at the output of the interferometer
  • the output optical fiber guided the transmitted i ed light to a photomultiplier, and the signal was recorded by a storage oscilloscope
  • Example 2 Electro-optically induced refractive index change
  • Electro-optical mate- nals e g liquid crystals
  • the electric field is supposed to be switched via two (micro)electrodes
  • the eligibility c ⁇ tei ia are the same as given above, also for the electro-optical materials
  • the arrangement shall comprise electrodes which presents an additional complexity
  • setting of the working point is subject to chemical reactions which are most probably less precisely controllable
  • Electromagnetic radiation as a control means of the adjuster member, preferably control light, is preferred
  • Example 3 Detection of antigen-antibody interaction
  • a furthei major advantage of our biosensor is that, the oppoi tunity of a pi oper adjustment of the working point of the MZ interferometer makes the i esults highly reproducible At the same time it can be set in a flexible manner

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  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (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

La présente invention concerne un dispositif de détection basé sur un interféromètre optique intégré ou à fibre optique, ledit dispositif comprenant un guide d'ondes optiques comprenant un chemin optique, au moins un élément d'ajustement comportant une couche adsorbée aux propriétés optiques non linéaires qui est susceptible de se modifier lors de l'exposition à la lumière, et au moins un récipient pour recevoir un échantillon, ledit élément d'ajustement et ledit récipient étant séparés spatialement. L'invention concerne également les utilisations dudit dispositif et des procédés permettant d'ajuster le signal de sortie dudit dispositif.
PCT/HU2009/000098 2008-12-03 2009-12-03 Dispositif de détection Ceased WO2010064058A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HUP0800733 2008-12-03
HU0800733A HU0800733D0 (en) 2008-12-03 2008-12-03 Sensor device

Publications (1)

Publication Number Publication Date
WO2010064058A1 true WO2010064058A1 (fr) 2010-06-10

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WO (1) WO2010064058A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220091031A1 (en) * 2020-09-18 2022-03-24 Salvus, Llc Interferometric Detection and Quantification System and Methods of Use in Chemical Processing

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EP0862075A1 (fr) 1997-02-27 1998-09-02 PIRELLI CAVI E SISTEMI S.p.A. Procédé pour réduire le nombre de refus dans la fabrication des composants optiques intégrés
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EP0862075A1 (fr) 1997-02-27 1998-09-02 PIRELLI CAVI E SISTEMI S.p.A. Procédé pour réduire le nombre de refus dans la fabrication des composants optiques intégrés
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220091031A1 (en) * 2020-09-18 2022-03-24 Salvus, Llc Interferometric Detection and Quantification System and Methods of Use in Chemical Processing

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