CN101493410A - Multichannel light microfluid sensor based on wavelength devision multiplex technology and sensing device - Google Patents
Multichannel light microfluid sensor based on wavelength devision multiplex technology and sensing device Download PDFInfo
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Abstract
The invention discloses a multi-channel optical microfluid sensor based on a wavelength division multiplexing technology, and a sensing device. The device comprises a broadband light source, an optical circulator, a spectral analysis device and the multi-channel optical microfluid sensor. The sensor consists of a substrate and a waveguide grating array and an optical microfluid resonant cavity array which are sequentially arranged on the substrate. The light output by the broadband light source is sent to the multi-channel optical microfluid sensor by the optical circulator, and a reflected light signal thereof brings resonant mode wavelength information of the microfluid resonant cavity back to a receiving terminal, and is sent to the spectral analysis device through the optical circulator. The device can effectively realize multi-channel optical microfluid sensing, and can be used for constructing a high-flux optical microfluid detection system. Parameters of a waveguide grating are designed to effectively control interaction between the waveguide grating and the optical microfluid resonant cavity, and effectively increase response peak value of an optical resonant spectral line, thus enhancing detection sensitivity. The device is applicable to various application occasions, and can be easily made and realize mass production with the prior art.
Description
[technical field]:
The present invention relates to can be used for various hyperchannel multiplex technique field, the especially wavelength-division multiplex of light microfluid sensing, belong to photo bio and chemical sensitisation technology based on the little resonance sensor of light.
[background technology]:
Unmarked biology sensor based on little resonant optical mode technology is directly measured interaction of molecules, can realize the Real Time Observation of bio-molecular interaction, has fluorescence owing to need not test analyte, special nature such as characteristic absorption or scattered band, the measuring object scope is expanded greatly, detectable toxin, protein, DNA, even whole cell behavior, thereby be medical diagnosis, the medicine development, the food monitoring, fields such as environmental monitoring provide strong analysis tool.
The light micro-resonant cavity utilizes total reflection that light is fully constrained in the microcavity, form standing wave and produce Echo Wall resonant mode (WhisperGallery Mode, WGM), owing to be total reflection, leakage loss is very little, thereby the very high Q value of the size that the light micro-resonant cavity can be very little acquisition, and the Q value can be up to 10
10When the testing concentration that is attached to the microcavity surface causes variations in refractive index, the effective refractive index of resonator cavity will change, thereby cause the resonance wavelength drift.By detecting wave length shift, can detect testing concentration and change.Sphere, annular and cylindricality are the common geometry of light micro-resonant cavity.As 2002, F.Vollmer utilizes the high Q value of light micro-resonant cavity, proposes a kind of new bio sensor (F.Vollmer, D.Braun based on microballoon, A.Libchaber, " Protein detection by opticalshift of a resonant microcavity, " Applied Physics Letters, 2002,80 (21): 4057-4059), the microballoon chamber has the highest quality factor in theory, but the fixed clamp difficulty is not easy to realize integrated.Little ring and little dish based on the plane light wave waveguide technology can adopt the mode of integrated optics photoetching to make, be easy to integrated on a large scale, therefore based on little ring (as A.Ksendzov, Y.Lin, " Integrated opticsring-resonator sensors for protein detection; " Optics Letters, 2005,30 (24): 3,344 3346; Yalcin, A.Popat, K.C.Aldridge, J.C., et al., " Optical sensing of biomolecules using microring resonators, " IEEE Journal ofSelected Topics in Quantum Electronics, 2006,12 (1): 148-155), little dish resonator cavity (as E.Krioukov, D.J.W.Klunder, A.Driessen, J.Greve, and C.Otto, " Sensor based on an integrated optical microcavity, " Opt.Lett.2002,27, the research work of optical sensor 512-514) obtains more concern.But the microcavity that photoetching produces is rough, greatly reduces the Q value of actual microcavity, thereby has lost the advantage of sensitivity.D.K.Armani etc. are by carrying out reflow treatment (D.K.Armani, T.J.Kippenberg, S.M.Spillance to little dish, k.J.Vahala, " Ultra high Q toroid microcavity on a chip, " Nature, 2003,421:925-928), microcavity Q is worth to surpass 10
7, utilizing this micro-resonant cavity, the Andrea M.Armani of this seminar etc. has further successfully realized detection (the Andrea M.Armani to single biomolecule, Rajan P.Kulkarni, ScottE.Fraser, Richard C.Flagan, Kerry J.Vahala, " Lable-free; single-molecule detection with opticalmicrocavities, " Science, 2007,317:783-787), the sensitivity advantage that has fully shown light micro-resonant cavity biology sensor.But for micro-resonant cavity and molecules detected can be interacted, these sensors all need to design and produce discrete sample cell or sample channel in addition, and it is complicated to make whole sensor-based system realize.Adopt the micro-resonant cavity sensor of capillary technique can realize uniting two into one of sample channel and sensing passage, simplify sensor construction greatly and improve reliability (as I.M.White, H.Oveys, and X.Fan, " Liquid-coreoptical ring-resonator sensors, " Opt.Lett., 2006,31,1319-1321).
But owing to lack the research multiplexing to hyperchannel, the micro-resonant cavity optical sensor still can't be realized big flux measurement at present.Exploration aspect micro-resonant cavity Photobiology sensor multiplexing, present rarely seen F.Vollmer of having etc. are by being coated with different oligonucleotides, realized the multiplexing spectral line detection (F.Vollmer of two microballoons, S.Arnold, D.Braun, I.Teraoka, A.Libchaber, " Multiplexed DNAquantification by spectroscopic shift of two mcirosphere cavities; " BiophysicalJounal, 2003,85:1974-1979), I.M.White etc. realize the multiplexing (I.M.White of little ring by be coated with different analytical reagents to be measured at the kapillary place, Hesam Oveys, Xudong Fan, " Integrated multiplexed biosensors based on liquid core optical ringresonantors and antiresonant refelcting optical waveguides; " Applied Physics letters, 2006,89:191106), both multiplex technique essence is identical, belong to space division multiplexing, only be applicable to the situation that detects different determinands simultaneously.In the communications field, then there is the researchist to realize separation ([the Shuichi Suzuki of WGM resonance line by making each microcavity size difference in the microcavity array, Yutaka Hatakeyama, Yasuo Kokubun, Sai Tak Chu, " Precise control of wavelength channel spacing ofmciroring resonator add-drop filter array; " Journal of Lightwave Technology, 2002,20 (4): 745-750), yet this method also is not suitable for detection, because will make making and operation become very complicated, causes detecting consistance variation or instability.In the development of biological and chemical sensing detection, realize that 96 wells of standard or the big flux measurement of 384 wells are the prerequisites that really can use and bring into play its advantage of Photobiology sensor, it is just very crucial to design novel multichannel light microfluid measurement scheme.
[summary of the invention]:
The objective of the invention is to solve the deficiency of above-mentioned little resonance sensor multiplex technique, propose a kind of multichannel light microfluid sensing device and method based on the waveguide optical grating wavelength-division multiplex.
Multichannel light microfluid sensor based on wavelength-division multiplex technique provided by the invention comprises substrate, is the waveguide optical grating array in the substrate, and the waveguide optical grating array is provided with the light microfluid resonant cavity array.Light microfluid resonant cavity array in the described light microfluid sensor is spatially corresponding one by one with the waveguide optical grating array, each waveguide optical grating resonance wavelength that same series connection in the waveguide optical grating array is made has nothing in common with each other, and centre wavelength corresponds respectively to wherein spectral line of the resonance dressing pedigree row of light microfluid resonator cavity.
Light miniflow resonator cavity in the described light microfluid resonant cavity array is microballoon, little ring, little dish or microtubule form.Waveguide optical grating in the described waveguide optical grating array is the waveguide grating structure, or optical fiber grating structure.
The present invention provides a kind of multichannel light microfluid sensing device based on wavelength-division multiplex technique simultaneously, and this sensing device comprises:
Wideband light source: be used to provide the sensing detection light source;
Optical circulator: the light that is used for respectively wideband light source being sent the above light microfluid sensor that provides is provided and accepts the light of light microfluid sensor reflected back;
Light microfluid sensor: the light microfluid sensor that provides more than the employing, light microfluid resonant cavity array in this sensor is spatially corresponding one by one with the waveguide optical grating array, each waveguide optical grating resonance wavelength that same series connection in the waveguide optical grating array is made has nothing in common with each other, and centre wavelength corresponds respectively to wherein spectral line of the resonance dressing pedigree row of light microfluid resonator cavity; By the resonant mode of evanescent field coupling exciting light miniflow resonator cavity, the reflected light signal of waveguide optical grating is also taken back receiving end with the resonant mode wavelength information of microfluid resonator cavity to reflectivity by selecting waveguide optical grating then with optionally;
Spectral analysis device: the reflectance spectrum to the waveguide optical grating array in the light microfluid sensor is analyzed, and can finish the multichannel light microfluid resonance of high sensitivity and detect simultaneously.
Spectral analysis device can adopt the form of wideband light source and the combination of tunable optic filter scanning probe, also can be tunable laser and combinations of detectors form.
Above-mentioned circulator also can adopt fiber coupler to replace.Above-mentioned waveguide optical grating can be various waveguide grating structures, also can be optical fiber grating structure.
Multichannel light microfluid method for sensing based on wavelength-division multiplex provided by the invention, the spectral analysis device that makes up with wideband light source and tunable optic filter is an example, its course of work is as follows:
The light of wideband light source arrives one road light microfluid sensor left side array to be measured by optical circulator, grating in the waveguide optical grating array of light microfluid sensor has different resonance wavelength, and the reflectivity of waveguide optical grating can guarantee optionally counterclockwise resonant mode by evanescent field coupling exciting light miniflow resonator cavity through design, further excite clockwise resonant mode by the forward transmitted of waveguide optical grating and the coupling of reverse transfer, then had following relation because of waveguide optical grating between two resonant modes:
A and b are respectively counterclockwise and clockwise resonant mode magnitude of energy, ω in the formula
aAnd ω
bBe respectively the resonance wavelength of counterclockwise and clockwise light microfluid resonator cavity resonant mode, τ
aAnd τ
bBe respectively the attenuation constant of counterclockwise and clockwise light microfluid resonator cavity resonant mode, u is the counterclockwise and clockwise light microfluid resonator cavity resonant mode mutual coupling factor that waveguide optical grating causes, S
InBe input light field amplitude,
Be the differential of a to time t,
Be the differential of b to time t, j is an imaginary unit.
By design alternative suitable the waveguide optical grating parameter such as the index modulation degree of depth, grating length etc., can change the u value, reach optimum coupling resonance, the light microfluid resonator cavity resonant mode close with this waveguide optical grating centre wavelength effectively strengthened, thereby overcome the shadow effect that exists between the light microfluid resonant cavity array because of light microfluid sensor, the resonance pectination spectral line that promptly solves between them blocks mutually, and can't extract the problem of each light microfluid sensor spectral line separately.When testing concentration changes, will cause that light microfluid resonator cavity effective refractive index changes, and then cause the drift of resonance wavelength.Because the reflectance spectrum width of waveguide optical grating is much larger than the spectrum width of light microfluid resonance spectrum, so will always can hold and carry light microfluid harmonic light spectrum signal in the reflectance spectrum of waveguide optical grating.The high precision spectral analysis device that employing is made up of tunable optic filter is analyzed the reflectance spectrum of waveguide optical grating array, can finish the multichannel light microfluid resonance of high sensitivity and detect simultaneously.
Advantage of the present invention and good effect:
1. propose light microfluid sensor wavelength-division multiplex technique and device, can realize the multichannel light microfluid sensing effectively, can be used for the structure of high flux light microfluid detection system based on waveguide optical grating.
2. by designing the depth of modulation (0.0001-0.05) of waveguide optical grating, the gap parameters such as (10nm-300nm) of grating length (20 μ m-150 μ m) and waveguide optical grating and resonator cavity, the effectively interaction of control wave guide grating and light microfluid resonator cavity, excite when can realize clockwise and counterclockwise resonant mode, increase the peak value of optical resonance spectral line response effectively, thereby improve detection sensitivity.
3. go for the light microfluid resonator cavity of multiple version based on the multiplex technique of waveguide optical grating, as light microballoon chamber, the little ring cavity of light, light little dish chamber and light microtubule chamber etc., can realize multiple multichannel light microfluid sensing scheme, thereby be suitable for various application occasions.
4. the light microfluid sensor multiplex technique based on waveguide optical grating that is proposed is made easily, can adopt existing waveguide fabrication technology to realize producing in batches.
[description of drawings]:
Fig. 1 is the multichannel light microfluid sensing device synoptic diagram that the present invention is based on waveguide optical grating;
Fig. 2 is that the waveguide optical grating coupling excites counterclockwise and clockwise light microfluid resonator cavity resonant mode synoptic diagram;
Fig. 3 is based on the synoptic diagram of the light microfluid sensor wavelength-division multiplex of waveguide optical grating;
Fig. 4 is the reflectance spectrum and the transmission spectrum of the light microfluid sensor-based system when adopting two waveguide optical gratings multiplexing;
Fig. 5 is based on the light microfluid sensor synoptic diagram of fiber grating and microscopic capillary;
Fig. 6 is based on the light microfluid sensor microarray synoptic diagram of wavelength-division multiplex technique.
[embodiment]:
Embodiment 1: based on the multichannel light microfluid sensing device of wavelength-division multiplex technique
As shown in Figure 1, this sensing device comprises: wideband light source 1, optical circulator 2, spectral analysis device 3, one road multichannel light microfluid sensor array 4 to be measured (being made of waveguide optical grating array 5 that sets gradually in the substrate and light microfluid resonant cavity array 6).
The light of wideband light source 1 output arrives the left side of one road multichannel light microfluid sensor array 4 to be measured by optical circulator 2, grating in the waveguide optical grating array 5 wherein has different resonance wavelength, can optionally excite the counterclockwise resonant mode of the light microfluid resonant cavity array 6 of different rank by the evanescent field coupling, further excited clockwise resonant mode by the forward transmitted of waveguide optical grating array 5 and the coupling of reverse transfer then, waveguide optical grating array 5 reflected light signals enter into spectral analysis device 3 through optical circulator 2.
Embodiment 2: based on the multichannel light microfluid method for sensing of wavelength-division multiplex technique
The sensing process of above-mentioned hyperchannel sensing device is as follows:
The light of wideband light source 1 output among Fig. 1 arrives one road multichannel light microfluid sensor array to be measured, 4 left sides by optical circulator 2, grating in the waveguide optical grating array 5 wherein has different resonance wavelength, can optionally excite the resonant mode of the light microfluid resonant cavity array 6 of different rank by the evanescent field coupling, waveguide optical grating array 5 reflected light signals carry resonant mode resonance wavelength information and enter into spectral analysis device 3 through optical circulator 2 then.
The excitation process of light microfluid resonant mode as shown in Figure 2, multiplex channel is made up of waveguide 13 and substrate 14, the incident light 9 that enters from the multiplex channel left side excites counterclockwise resonant mode 7 by evanescent field 10 light microfluid resonator cavity 6, pass through the retroactive effect of waveguide optical grating 5 then, excite clockwise resonant mode 8 at light microfluid resonator cavity 6, then had following relation because of waveguide optical grating between two resonant modes:
A and b are respectively counterclockwise and clockwise resonant mode magnitude of energy, ω in the formula
aAnd ω
bBe respectively the resonance wavelength of counterclockwise and clockwise light microfluid resonator cavity resonant mode, τ
aAnd τ
bBe respectively the attenuation constant of counterclockwise and clockwise light microfluid resonator cavity resonant mode, u is the counterclockwise and clockwise light microfluid resonator cavity resonant mode mutual coupling factor that waveguide optical grating causes, S
InBe input light field amplitude,
Be the differential of a to time t,
Be the differential of b to time t, j is an imaginary unit.By design alternative suitable the waveguide optical grating parameter such as the index modulation degree of depth (0.0001-0.05), ginseng such as the gap (10nm-300nm) of grating length (20 μ m-150 μ m) and waveguide optical grating and resonator cavity etc., can change the u value, reach optimum coupling resonance, the light microfluid resonator cavity resonant mode close with this waveguide optical grating centre wavelength greatly strengthened, other light 11 transmissions are passed through, thereby overcome the shadow effect that exists between micro-resonant cavity array because of light microfluid sensor, the resonance pectination spectral line that promptly solves between them blocks mutually, and can't extract the problem of each light micro-resonant cavity sensor spectral separately.The design of parameter can be adopted the softwares such as FULLWAVE of RSoft to carry out designing and calculating and obtain, and is 0.0001-0.05 as the index modulation degree of depth, and grating length is 20 μ m-150 μ m, and the gap of waveguide optical grating and resonator cavity is 10nm-300nm.The radial distribution of the resonant mode that light microfluid resonator cavity inner wall surface can be excited depends on biomolecule refractive index n to be measured
1, promptly
J
mBe m rank Bessel's functions, k
0 lBe the l rank amplitude of WGM mould wave vector radially in the vacuum, when testing concentration changes, will cause that light microfluid resonator cavity effective refractive index changes, change resonant mode and then cause the drift of resonance wavelength.There is stable relations n=1.33828+0.179258x-0.380008x between the molar percentage x as the refractive index of ethanol water and ethanol
2+ 0.351867x
3+ 0.124503x
4, light microfluid resonator cavity resonance wavelength moves with refractive index and has relation～10nm/RIU, and RIU is a refractive index unit in the formula.Can instead push away concentration information by these two relations.Because the reflectance spectrum width of waveguide optical grating is much larger than the spectrum width of light microfluid resonance spectrum, so will always can hold and carry light microfluid harmonic light spectrum signal in the reflectance spectrum in the reflected light 12 of waveguide optical grating.The high precision spectral analysis device that employing is made up of tunable optic filter is analyzed the reflectance spectrum of waveguide optical grating array, can finish the multichannel light microfluid resonance of high sensitivity and detect simultaneously.
In the inventive method:
1. spectral analysis device can adopt the form of wideband light source and the combination of tunable optic filter scanning probe, also can be tunable laser and combinations of detectors form or other raster pattern spectroanalysis instruments.
2. the light microfluid resonator cavity can be a microballoon, little ring, little dish or microtubule form.Above-mentioned circulator also can adopt fiber coupler to replace.
3. waveguide optical grating can be various waveguide grating structures, also can be optical fiber grating structure.
4. can be used for various biologies, chemical hyperchannel Application in Sensing occasion based on refractometry.
3: two passage light microfluids of embodiment sensing is multiplexing for example
Two passages multiplexing in as shown in Figure 3, the sensing multiplex channel is made up of waveguide 13 and substrate 14, waveguide optical grating array 5 is made in the waveguide 13, and two waveguide optical gratings have different reflection kernel wavelength, above waveguide optical grating array 5, be placed with the light microfluid resonator cavity 6 of same structural parameters, incident light is coupled in the light microfluid resonator cavity 6 by evanescent field 10, has excited counterclockwise resonant mode 7 and clockwise resonant mode 8.The reflected signal 15 of waveguide optical grating array 5 and reflected signal 16 will carry the resonance wavelength signal (seeing the reflectance spectrum among Fig. 4) of resonant mode.
Embodiment 4: applicating example
Multichannel light microfluid sensing device of the present invention and method can be applied to the micro-resonant cavity bio-sensing based on microscopic capillary.
Its localized sensor structure as shown in Figure 5.In microscopic capillary 18 inwall solidified biological detectable 19, microfluid test sample 20 is carried from microscopic capillary 18.Microscopic capillary 18 constitutes micro-resonant cavity perpendicular to axial direction in tube wall, the light wave of propagating in its resonator cavity penetrates in the microfluid test sample 20 in the microscopic capillary 18 by the disappearance wave field and surveys.
When the microfluid 17 of carrying biomolecule to be detected passed through kapillary, the bio-molecular interaction of biological detection reagent 19 and test sample 20 changed refractive index, thereby changed resonance wavelength.Input light 9 excites the resonant mode of micro-resonant cavity by the evanescent field coupling under fiber grating 22 effects.Can determine the information of light microfluid resonator cavity resonance wavelength by the reflectance spectrum of analyzing fiber grating, and then know the information of biomolecule action by inference, be i.e. the concentration that mutually combines of biological detection reagent 19 and test sample 20.Fig. 6 combines light microfluid wavelength-division multiplex technique of the present invention with empty branch technology, promptly the diverse location in same microscopic capillary solidifies different detectable arrays 23, import a plurality of microfluids then simultaneously, as microfluid 24, microfluid 25, microfluids 26 etc. can constitute the microarray assay device, can finish detection by the light signal of analyzing in sensing multiplex channel 28 (by substrate 14, waveguide 13 and the waveguide optical grating array 5 that is made in the waveguide 13 are formed) 27.
Claims (5)
1, a kind of multichannel light microfluid sensor based on wavelength-division multiplex technique is characterized in that this sensor comprises substrate, is the waveguide optical grating array in the substrate, and the waveguide optical grating array is provided with the light microfluid resonant cavity array.
2, the multichannel light microfluid sensor based on wavelength-division multiplex technique according to claim 1, it is characterized in that the light microfluid resonant cavity array in the described light microfluid sensor is spatially corresponding one by one with the waveguide optical grating array, each waveguide optical grating resonance wavelength that same series connection in the waveguide optical grating array is made has nothing in common with each other, and centre wavelength corresponds respectively to wherein spectral line of the resonance dressing pedigree row of light microfluid resonator cavity.
3, the multichannel light microfluid sensor based on wavelength-division multiplex technique according to claim 1 and 2 is characterized in that the light miniflow resonator cavity in the described light microfluid resonant cavity array is microballoon, little ring, little dish or microtubule form.
4, the multichannel light microfluid sensor based on wavelength-division multiplex technique according to claim 1 and 2 is characterized in that the waveguide optical grating in the described waveguide optical grating array is the waveguide grating structure, or optical fiber grating structure.
5, a kind of multichannel light microfluid sensing device based on wavelength-division multiplex technique is characterized in that this sensing device comprises:
Wideband light source: be used to provide the sensing detection light source;
Optical circulator: the light that is used for respectively wideband light source being sent is incorporated into claim 1 or 2 described light microfluid sensors and accepts the light of light microfluid sensor reflected back;
Light microfluid sensor: adopt claim 1 or 2 described light microfluid sensors, light microfluid resonant cavity array in this sensor is spatially corresponding one by one with the waveguide optical grating array, each waveguide optical grating resonance wavelength that same series connection in the waveguide optical grating array is made has nothing in common with each other, and centre wavelength corresponds respectively to wherein spectral line of the resonance dressing pedigree row of light microfluid resonator cavity; By the resonant mode of evanescent field coupling exciting light miniflow resonator cavity, the reflected light signal of waveguide optical grating is also taken back receiving end with the resonant mode wavelength information of miniflow resonator cavity to reflectivity by selecting waveguide optical grating then with optionally;
Spectral analysis device: the reflectance spectrum to the waveguide optical grating array in the light microfluid sensor is analyzed, and can finish the multichannel light microfluid resonance of high sensitivity and detect simultaneously.
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| CN112903545A (en) * | 2021-03-16 | 2021-06-04 | 华侨大学 | Multi-channel sensing system and detection method |
| CN113702297A (en) * | 2021-08-10 | 2021-11-26 | 哈尔滨工业大学（深圳） | Biosensor system and method for detecting biological sample by using same |
| CN113702297B (en) * | 2021-08-10 | 2023-08-15 | 哈尔滨工业大学（深圳） | Biosensor system and method for detecting biological sample by using same |
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