CN100565188C - The application process of optical fiber biosensor - Google Patents
The application process of optical fiber biosensor Download PDFInfo
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- CN100565188C CN100565188C CN 200710058309 CN200710058309A CN100565188C CN 100565188 C CN100565188 C CN 100565188C CN 200710058309 CN200710058309 CN 200710058309 CN 200710058309 A CN200710058309 A CN 200710058309A CN 100565188 C CN100565188 C CN 100565188C
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Abstract
The invention discloses a kind of application process of optical fiber biosensor.Described optical fiber biosensor comprises sample cell, one section coreless fiber in the sample cell, the input optical fibre at the two ends of coreless fiber and output optical fibre.Process with this sensor biomaterial comprises: at first coat the affinity membrane that can combine with detected biomaterial in the coreless fiber circumferential surface, so the generation of the certain wavelengths of sensor is interfered greatly or interfered minimum; The liquid that will contain the biomaterial of needs detection then injects sample cell, then biomaterial combines with affinity membrane, affinity membrane thickness increases, thereby make the sensor certain wavelengths interfere greatly or interfere the wavelength of minimum correspondence to produce corresponding the variation, measure and interfere greatly or interfere the variation of the optical wavelength of minimum correspondence can obtain biomaterial information.The invention has the advantages that the sensor construction of employing is simple, make easily that test process is simple, be easy to realize, highly sensitive.
Description
Technical field
The present invention relates to a kind of application process of optical fiber biosensor, particularly a kind of application process based on the optical fiber biosensor of high-order mode interference in the optical fiber belongs to the optical fibre bio sensory field.
Background technology
Biology sensor is the important means that is used for the detection and Identification bioactive materials, and these active materials can be enzyme, protein, DNA, antibody, antigen, biological membrane etc.Biology sensor is being brought into play important role at the aspects such as exploitation, Food Inspection and toxic gas detection of the diagnosis of microorganism detection, drug screening, blood analysis, DNA analysis, antigen/antibody analysis, all kinds of diseases and detection, new drug.Existing biology sensor can be divided into microbiological sensor, immunosensor, tissus sensor, cell sensor, enzyme sensor, DNA sensor etc. by its function.In the biology sensor that constitutes by various different principle, optical biosensor, particularly optical fiber biosensor with its high sensitivity, can realize quick online detection and can be used for distinguishing feature such as on-the-spot detection and be subjected to general attention and developed rapidly.Adopt surface plasma body resonant vibration technology (Surface Plasmon Resonance, be called for short SPR) optical biosensor development with surprising rapidity especially since nineteen eighty-two Nylander etc. is used for the immunosensor field with the SPR technology first, and be used widely.SPR is at the wave of oscillation of the free electron of metal and dielectric interface propagation and the light wave fields generation resonance of propagating in dielectric with specific wavelength and polarization state, and makes the energy of light wave produce a kind of physical phenomenon of decay.When metal film and thickness, specific inductive capacity of being deposited on the material on the metal etc. changed, respective change can take place in SPR resonance wavelength or resonant angle.If bioactive materials is fixed on the metal film, when with another kind of bioactive materials generation binding specificity, because the variation of film thickness, SPR resonance wavelength or resonant angle can change.So, but the specificity combination between the different bioactive materials of employing SPR technology detection and Identification.At present, the SPR technology is widely used in the research of various sufacings, has become gordian technique and method in the bio-sensing, also becomes the important means of microorganism detection and research molecular reaction dynamics simultaneously.The method of sputter is generally adopted in the making of metal film among the SPR, requires equipment and other condition higher.The thickness of the required metal film of SPR is in tens nanometers, and needing accurately, control could obtain good SPR effect.Metal commonly used is materials such as gold, silver, and to Jin Eryan, its SPR resonance wavelength is at red spectral band, and will select the suitable polarization direction.
Summary of the invention
The object of the present invention is to provide a kind of application process of optical fiber biosensor, with this method detection of biological material have operating process simple, be easy to characteristics such as realization, sensitivity height.
The present invention is realized by following technical proposals, a kind of application process of optical fiber biosensor, described optical fiber biosensor comprises the sample cell 104 of sealing, one section coreless fiber 102 is set in the sample cell, and the two ends of coreless fiber are docked single mode input optical fibre 101 and single mode output optical fibre 107 without acceptance of persons.Detect the method for the biomaterial that comprises enzyme, cell, gene, antigen, antibody with above-mentioned optical fiber biosensor, it is characterized in that comprising following process:
1, at first coat the affinity membrane that can combine with detected biomaterial in coating of coreless fiber circumferential surface or dipping, so the single-mode optics that transmits by the single mode input optical fibre coreless fiber be fixed on the high-order modes that produce a plurality of circle symmetries in the affinity membrane of its circumferential surface and the multimode lightguide that surrounding medium constitutes, high-order mode is propagated along described multimode lightguide, produce multiple-mode interfence at the interface of coreless fiber and single mode output optical fibre, produce in certain wavelengths and interfere greatly or interfere minimum;
2, the liquid that will contain the biomaterial of needs detection then injects sample cell, then biomaterial combines with affinity membrane, affinity membrane thickness increases, so the propagation constant of the high-order mode of propagating in multimode lightguide is changed, interfere greatly or interfere the wavelength of minimum correspondence to produce corresponding the variation thereby make, measure to interfere greatly or interfere the variation of the optical wavelength of minimum correspondence can obtain the situation of coreless fiber surface biological affinity membrane generation combination, thus the detection and Identification biomaterial to be measured amount that whether exists and exists how much or concentration information.
The characteristics of optical fiber biosensor involved in the present invention are: 1) sensor construction is extremely simple, makes easily, only needs common single mode telecommunication optical fiber and coreless fiber, and the optics that uses general optical fiber splicer can finish sensor is made.Because sensor itself is cheap, can realize disposable use truly.2) can adopt common chemical and other method that biomaterial is fixed on the coreless fiber surface, and need not special technique and equipment.3) optical wavelength detects and can adopt general spectroanalysis instrument to finish.4) have the Wavelength-encoding feature, and, be suitable for long-range and online detection because I/O optical fiber is single-mode fiber.
Description of drawings
Fig. 1 is the optical fiber biosensor structural representation.
Among the figure: 101 is the single mode input optical fibre; 102 is coreless fiber; 103 is the affinity membrane that is fixed on the biomaterial on coreless fiber surface; 104 is sample cell; 105 is the sample inlet; 106 is the optical fiber fixing glue; 107 is the single mode output optical fibre.
Fig. 2 is an optical fibre bio sensing experiment device instrument synoptic diagram.
Among the figure: 100 is optical fiber biosensor; 201 is wideband light source; 202 is Transmission Fibers; 203 is Water Tank with Temp.-controlled; 204 is wavelength demodulation device.
Fig. 3 is actual measurement antigen/antibody course of reaction curve map.
Embodiment
Below in conjunction with accompanying drawing the specific embodiment of the present invention is elaborated.As shown in Figure 1, single-mode fiber 101 adopts standard single-mode fiber (G652), and its core diameter is 8.2 μ m, and cladding diameter is 125 μ m, numerical aperture 0.14.At first its protective finish is removed, used the optical fiber cutting knife that its end face is cut into and its axis normal then.Coreless fiber 102 is pure silica fibre, and its diameter is 125 μ m.Use the optical fiber cutting knife that its end face is cut into and its axis normal, afterwards, the single-mode fiber 101 after the end face processing is put into optical fiber splicer with coreless fiber 102 two fused fiber splices are in the same place.The 55mm place uses the optical fiber cutting knife that it is cut off on coreless fiber, and itself and another section single-mould fiber 107 is welded together.
Sample cell housing 104 is made by the glass tube of external diameter 5mm internal diameter 3mm, and the case bonding of using Fibre Optical Sensor that epoxy resin will be made of single-mode fiber-coreless fiber-single-mode fiber and sample cell 104 together.Fully solidifying the back at epoxy resin is cleaned optical fiber and sample cell by sample inlet 105 injection hydrogen peroxide.Afterwards, add 2.5% glutaraldehyde solution, room temperature left standstill one hour, and adding concentration then is the rabbit igg antibody of 10 μ g/ml, treat that antibody covers the surface of coreless fiber 102 fully after, form the affinity membrane 103 that constitutes by antibody after one hour.Add damping fluid afterwards, thereby finish the making of optical fiber biosensor.
Fig. 2 is an optical fibre bio sensing experiment device instrument synoptic diagram.Wherein 100 is optical fiber biosensor.The output spectrum scope of wideband light source 201 is 1520-1565nm, and output power is 5mW; May in experiment, optical fiber biosensor 100 be placed Water Tank with Temp.-controlled 203 to the influence of measuring in order to eliminate temperature variation.The temperature of Water Tank with Temp.-controlled 203 is set in 25 ℃, and its temperature stability is ± 0.1 ℃.In the experiment, insert sample and inject conduit on sample inlet 105, optical fiber biosensor 100 is fixed on the support, and optical fiber biosensor 100 places Water Tank with Temp.-controlled 203 with support.204 is fibre optic spectral analyzer, as spectrum record and Wavelength demodulation equipment.
When the temperature stabilization of Water Tank with Temp.-controlled 203 after 25 ℃, inject conduit by sample and inject damping fluid, on the transmission spectrum of fibre optic spectral analyzer 204 records, determine a trough (interference minimal value) that produces by multiple-mode interfence, and measure the wavelength of this trough correspondence.The wavelength value of corresponding damping fluid is as the reference value of measuring.Afterwards, with the damping fluid emptying, inject the detected liquid that contains antigen.Because with the affine film of biologically active (antibody) 103 that is fixed on coreless fiber 102 surfaces specificity taking place, antigen combines, the propagation constant of the high-order mode of propagating in coreless fiber 102 is changed, and the trough that multiple-mode interfence is produced moves to the long wave direction, and its amount of movement is directly proportional with the binding capacity of antibody-antigen.By fibre optic spectral analyzer 204 record trough corresponding wavelength over time, can obtain the dynamic process and the binding capacity of antibody-antigen combination, thereby but whether have the information such as what or concentration that have the amount of the antigen of specificity binding characteristic and existence with the antibody that is fixed on coreless fiber 102 surfaces in the detection and Identification survey liquid to be measured.
Fig. 3 is actual measurement antigen/antibody reaction experiment result.Can find out along with the increase of time, constantly have antibody-antigen to take place thus, the thickness of the affinity membrane 103 on coreless fiber 102 surfaces is in continuous increase, thereby the trough (interference minimal value) that multiple-mode interfence produces in the coreless fiber 102 will move to the long wave direction.
By above embodiment as can be seen, the optical fiber biosensor that the present invention relates to is made very simple, need not the metal film of the nanometer grade thickness in the picture SPR technology, and employed optical fiber is conventional optical fiber, is easy to acquisition and cheap.The fixing of biomaterial can adopt any existent method to carry out.
The method that bioactive materials is fixed to the coreless fiber surface is multiple in addition, and as absorption method, sol-gel process, covalent bond is legal and LB mould technology etc., they are prior art.
Those skilled in the art are clear, and thought of the present invention can adopt the alternate manner beyond the above-named embodiment to realize.
Claims (1)
1, a kind of application process of optical fiber biosensor, described optical fiber biosensor comprises the sample cell (104) of sealing, one section coreless fiber (102) is set in the sample cell, the two ends of coreless fiber are docked single mode input optical fibre (101) and single mode output optical fibre (107) without acceptance of persons, comprise enzyme with above-mentioned optical fiber biosensor detection, cell, gene, antigen, the biomaterial of antibody, method step is that the liquid that will contain this biomaterial of needs detection injects sample cell, coat the affinity membrane that can combine in coating of coreless fiber circumferential surface or dipping with detected biomaterial, the increase of affinity membrane thickness makes interferes interference of light greatly or interfere the optical wavelength of minimum correspondence to change, measure the variation of this optical wavelength can detection and Identification liquid in what or the concentration information of amount of the existence of biomaterial and existence, it is characterized in that:
Described affinity membrane is that coating or dipping are coated in the coreless fiber circumferential surface, so the single-mode optics that transmits by the single mode input optical fibre coreless fiber be fixed on the high-order modes that produce a plurality of circle symmetries in the affinity membrane of its circumferential surface and the multimode lightguide that surrounding medium constitutes, high-order mode is propagated along described multimode lightguide, interface at coreless fiber and single mode output optical fibre produces multiple-mode interfence, produce to interfere greatly or interfere minimum in certain wavelengths, affinity membrane thickness increases, so the propagation constant of the high-order mode of propagating in multimode lightguide is changed, interferes greatly or interfere the wavelength of minimum correspondence to produce corresponding the variation thereby make.
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Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101246119B (en) * | 2007-03-23 | 2011-06-08 | 国家纳米技术与工程研究院 | Optical fiber biological sensing system |
| WO2010090514A1 (en) * | 2009-02-04 | 2010-08-12 | Ostendum Holding B.V., Et Al | System for analysis of a fluid |
| CN103969221A (en) * | 2013-01-25 | 2014-08-06 | 中国计量学院 | Optical fiber refractive index sensor based on single mode-fine core-multimode-single mode structure |
| US9702813B2 (en) | 2014-07-23 | 2017-07-11 | Infineon Technologies Ag | Sensing systems and methods using a coupling structure |
| CN104251909B (en) * | 2014-09-18 | 2016-05-11 | 贵州大学 | A kind of biosensor structure and preparation method thereof |
| CN106596452B (en) * | 2016-12-30 | 2019-03-22 | 重庆理工大学 | The detection method of these hydrogen sulfide gas sensor and preparation method thereof and concentration of hydrogen sulfide |
| CN108759883A (en) * | 2018-05-21 | 2018-11-06 | 杭州光飞秒科技有限公司 | Mach-Zehnder interferometer in the optical fiber cable of straight waveguide is inscribed based on femtosecond laser |
| CN108917857A (en) * | 2018-09-13 | 2018-11-30 | 东北大学 | A kind of long-distance surface plasmon resonance sensor based on coreless fiber |
| CN109991193B (en) * | 2019-04-22 | 2021-07-13 | 重庆理工大学 | Method for manufacturing coreless multimode optical fiber hydrogen sulfide gas sensor, sensor thereof and method for detecting concentration of hydrogen sulfide gas |
| CN110308115A (en) * | 2019-06-14 | 2019-10-08 | 深圳大学 | A kind of interference-type optical fiber spr sensor |
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