CN101545899B - Optical fibre micro-fluidic biological sensor and preparation method thereof - Google Patents

Optical fibre micro-fluidic biological sensor and preparation method thereof Download PDF

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CN101545899B
CN101545899B CN 200910039129 CN200910039129A CN101545899B CN 101545899 B CN101545899 B CN 101545899B CN 200910039129 CN200910039129 CN 200910039129 CN 200910039129 A CN200910039129 A CN 200910039129A CN 101545899 B CN101545899 B CN 101545899B
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optical fiber
micro
fluidic
kapillary
light source
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CN101545899A (en
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杨中民
冯洲明
徐善辉
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South China University of Technology SCUT
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South China University of Technology SCUT
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Abstract

The invention provides an optical fibre micro-fluidic biological sensor and a preparation method thereof. The optical fibre micro-fluidic biological sensor comprises a light source, a transmission light path, a biological sample stream, a signal light acquisition light path and a signal processing device. The preparation method of the optical fibre micro-fluidic biological sensor comprises the following steps: pulling the middle local position of optical fiber to be filament with diameter being less than 10 micrometers and length being 1mm-10cm; tightly winding the pulled filament on the outer wall of a capillary with diameter being less than 2mm; leading optical coupling sent by the light source to enter one end of the optical fiber, and connecting the other end of the optical fiber with a data processing system. A biological sample with fluorescence labeling is led into the capillary, and the concentration of the biological sample is measured according to optical information of fluorescence intensity and the like. The invention can replace the prior evanescent wave test technology of preparing the optical fiber into an optical fiber probe, combines with the micro-fluidic technology and is convenient for the dynamic real-time detection of the trace biological sample.

Description

A kind of optical fibre micro-fluidic biological sensor and preparation method thereof
Technical field
The present invention is a kind of optical fiber biosensor, particularly relates to a kind of optical fibre micro-fluidic biological sensor and preparation method thereof.
Background technology
Optical fiber biosensor has that the insulation shielding effect is good, anti-electromagnetic interference capability is strong, remote-controlled real time dynamic measurement and receive extensive concern; In optical fiber biosensor; Biologic sensor for fast travelling waves of optical fibre be should have the most a kind of; This sensor is in the residing medium of fibre-optical probe, to produce evanescent wave when utilizing light wave in optical fiber, to transmit with the mode of total reflection; This evanescent wave excites through absorption or with biological compatible reaction and is connected the biological substance that is marked with fluorescence molecule on the detecting head surface, thereby realizes the mensuration to material concentration to be measured.
Traditional biologic sensor for fast travelling waves of optical fibre mainly is to utilize optical fiber as probe, and has adopted resolution element in a large number at excitation light path and signal detection light paths, as patent (Huang Huijie, Zhai Junhui etc. biologic sensor for fast travelling waves of optical fibre, ZL01139224.X).The researchist improves excitation light path and signal detection light paths subsequently, utilizes optical fiber to substitute excitation light path and signal detection light paths, like patent (Shi Hanchang; Long Feng; He Miao. biosensor of full fiber optic evanescent wave, application number: 200610089497.4 and Cao Wanghe, pay Yao; Sieve former times is virtuous. a kind of optical fiber biological sensor, application number: 200710011932.6).Improve through these, improved the transfer efficiency and the signal to noise ratio (S/N ratio) of light, simplified apparatus structure, improved reliability, be beneficial to the miniaturization of instrument.All fail to change with optical fiber as probe, directly insert situation in the sample cell but these improve, to have increased the difficulty that fibre-optical probe is handled, and might bring pollution biological specimen; Because fibre-optical probe itself carries the bioprobe molecule, make this type sensor be not easy to carry out kinetic measurement in addition.
Summary of the invention
The objective of the invention is to existing fiber biology sensor inefficiency, be not easy to the problem of kinetic measurement, a kind of micro-fluidic optical fiber biosensor and preparation method thereof is provided.The present invention realizes through following technical scheme:
A kind of micro-fluidic optical fiber biosensor; Comprise light source, delivery optics, biological sample stream, flashlight collection light path and signal processing apparatus; Said delivery optics is a Transmission Fibers, and an end of Transmission Fibers is connected with light source, and the other end is connected with signal processing apparatus; Said biological sample stream adopts kapillary; Some is wound in formation flashlight collection light path on the outer wall capillaceous Transmission Fibers; The position that on kapillary, is wound with optical fiber all is coated with the high-reflecting film of one deck exciting light and flashlight together with the optical fiber outside surface at this place, and promptly all there is coatings at exposed position in this zone.In kapillary, feed and be with fluorescently-labeled biological specimen; Measure biological sample concentration according to optical information such as fluorescence intensities; The alternative evanescent wave measuring technology that at present optical fiber fabrication is become optical fiber probe of the present invention; And combine with microflow control technique, the dynamic real-time of being convenient to micro-biological specimen detects.The course of work of said micro-fluidic optical fiber biosensor is: from the exciting light of light source output through the kapillary outer wall time; Exciting light gets into sample flow path; Excite biological sample, the fluorescence that biological sample sends is exported from the signal Processing end through being coupled into winding optical fiber.
Above-mentioned micro-fluidic optical fiber biosensor, the diameter that is wound in the optical fiber on the kapillary is less than 10 μ m, and length is 1mm~10cm.
Above-mentioned micro-fluidic optical fiber biosensor, the optical fiber that forms flashlight collection light path closely is around on the kapillary.
Above-mentioned micro-fluidic optical fiber biosensor, the cross sectional shape of said optical fiber are circle, rectangle or D type, and the material of said optical fiber is glass, plastics or crystal, and said optical fiber is single mode or multimode optical fiber.
Above-mentioned micro-fluidic optical fiber biosensor, said optical fiber are the microstructure photonic crystal fiber.
Above-mentioned micro-fluidic optical fiber biosensor, said material capillaceous is glass or plastics, cross sectional shape capillaceous is circle or rectangle.
Above-mentioned micro-fluidic optical fiber biosensor, said kapillary refractive index is more than or equal to the refractive index of twining fibre cladding.
Above-mentioned micro-fluidic optical fiber biosensor, said light source are laser instrument or fluorescence light source.
The preparation method of above-mentioned micro-fluidic optical fiber biosensor comprises the steps:
(1) part with Transmission Fibers is drawn into diameter less than 10 μ m, and length is the fiber-optic filament of 1mm~10cm;
(2) fiber-optic filament that step (1) is obtained closely is wrapped on the outer wall capillaceous of diameter less than 2mm, then at the high-reflecting film that twines position plating one deck exciting light and flashlight;
The optically-coupled of (3) light source being sent gets into an end of Transmission Fibers, and the other end of Transmission Fibers is connected with signal processing apparatus;
(4) feed in the kapillary and be with fluorescently-labeled biological specimen.
The method for making of micro-fluidic optical fiber biosensor of the present invention may further comprise the steps:
(1) part with Transmission Fibers is drawn into diameter less than 10 μ m, and length is the fiber-optic filament of 1mm~10cm;
(2) fiber-optic filament that step (1) is obtained closely is wrapped on the outer wall capillaceous of diameter less than 2mm, then at the high-reflecting film that twines position plating one deck exciting light and flashlight;
The optically-coupled of (3) light source being sent gets into an end of optical fiber, and the other end of optical fiber is connected with data acquisition system (DAS) 7;
(4) be with fluorescently-labeled biological specimen with feeding in the kapillary.
The micro-fluidic optical fiber biosensor that the present invention proposes contains light source and delivery optics, sample flow path, flashlight collection light path and signal processing apparatus; It is characterized in that said optical fiber can be formed by the drawing of materials such as glass, plastics, monocrystalline; Its cross section structure comprises fiber core and covering; The cross sectional shape of covering can be multiple cross sectional shapes such as circle, rectangle, rectangle, D type, and mode configuration can be single mode, multimode or microstructure photonic crystal fiber; Said kapillary is to be made by the optical material of light-permeable (like glass, plastics etc.), and its refractive index is more than or equal to the fibre cladding refractive index, and its cross sectional shape can be circle, rectangle, rectangle etc.; Said excitation source can be a laser instrument, also can be various fluorescence light sources; Said high-reflecting film can be the film that metal, organic and inorganic component form, and also can be the combination of these several kinds of component films.
The present invention compared with prior art has following beneficial effect:
Micro-fluidic optical fiber biosensor of the present invention can be realized separating of optical fiber and test biological sample, avoids the pollution to biological specimen; Because optical fiber does not carry the bioprobe molecule, the numerous and diverse program that therefore can avoid making probe; Use capillaceous has reduced the use amount of biological specimen, and biological specimen flows in kapillary, can realize that dynamic real-time detects.It is luminous that the present invention utilizes optical excitation to be marked with the biological substance of fluorescence molecule, thereby realize the microcurrent controlled capillary tube biology sensor of biological detection, can be used for fields such as medical diagnosis, drug screening, environment and food inspection.
Description of drawings
Fig. 1 is the structural representation of micro-fluidic optical fiber biosensor in the embodiment.
Fig. 2 is the structural representation of the micro-fluidic optical fiber biosensor of electrophoretype in the embodiment.
Embodiment
Below in conjunction with accompanying drawing practical implementation of the present invention is described further.
Please with reference to Fig. 1, visible by Fig. 1, the micro-fluidic optical fiber biosensor of the present invention comprises light source 1 and delivery optics (being Transmission Fibers 2), sample flow path 4 → 5 → 6, flashlight collection light path 5 and signal processing apparatus 7.It is the Ar ion laser of 488nm that light source 1 adopts wavelength, and power is 50mW; Optical fiber 2 adopts the multimode quartz glass optical fiber, and core diameter is that 62.5 μ m, cladding diameter are 125 μ m; It is that 10 μ m, length are the fiber-optic filament 3 of 3cm that Transmission Fibers 2 draws the awl machine to draw out diameter through optical fiber; It is that 2mm, internal orifice dimension are the quartz ampoule of 1.2mm that kapillary 4 adopts diameter; The fiber-optic filament that draws is twined 1~3 circle at the kapillary outer wall, twining the district through silver mirror reaction plating one deck silverskin then; The winding district of fiber-optic filament on kapillary forms flashlight and gathers light path 5; Signal processing apparatus adopts the spectrometer that has InGaAs detector, photomultiplier (PMT), and links to each other with computing machine.As test organisms liquid, in sample cell 9, inject the ethanolic solution of rhodamine with rhodamine, open peristaltic pump 6, rhodamine solution gets into waste liquid pool 10 from sample cell through kapillary.Open light source; 488nm laser gets into fiber-optic filament 3 through Transmission Fibers 2, and optical fiber footpath refinement makes the part zlasing mode become evanescent wave, becomes radiation mode through curved fiber again; After the emission of optical fiber outside surface reflectance coating, get in the kapillary; Excite rhodamine to send red fluorescence, the optical fiber that the part red fluorescence is twined the district is caught, through flashlight delivery optics 2 entering signal treating apparatus 7.
In the present embodiment, peristaltic pump 6 can replace through the high-voltage power supply device, and is as shown in Figure 2, and kapillary can form through drawing through the part than the thickness pipe, like the biological specimen runner pipe 8 among the figure.

Claims (9)

1. micro-fluidic optical fiber biosensor; Comprise light source, delivery optics, biological sample stream, flashlight collection light path and signal processing apparatus; It is characterized in that said delivery optics is a Transmission Fibers, an end of Transmission Fibers is connected with light source, and the other end is connected with signal processing apparatus; Said biological sample stream adopts kapillary; Some is wound in Transmission Fibers on the outer wall capillaceous, forms flashlight and gathers light path; The position that on kapillary, is wound with optical fiber all is coated with the high-reflecting film of one deck exciting light and flashlight together with the optical fiber outside surface at this place.
2. micro-fluidic optical fiber biosensor according to claim 1, the diameter that it is characterized in that being wound in the optical fiber on the kapillary is less than 10 μ m, and length is 1mm~10cm.
3. micro-fluidic optical fiber biosensor according to claim 1 is characterized in that the optical fiber that forms flashlight collection light path closely is around on the kapillary.
4. micro-fluidic optical fiber biosensor according to claim 1 is characterized in that the cross sectional shape of said optical fiber is circle, rectangle or D font, and the material of said optical fiber is glass, plastics or crystal, and said optical fiber is single mode or multimode optical fiber.
5. micro-fluidic optical fiber biosensor according to claim 1 is characterized in that said optical fiber is the microstructure photonic crystal fiber.
6. micro-fluidic optical fiber biosensor according to claim 1 is characterized in that said material capillaceous is glass or plastics, and cross sectional shape capillaceous is circle or rectangle.
7. according to each described micro-fluidic optical fiber biosensor of claim 1~6, it is characterized in that said kapillary refractive index is more than or equal to the refractive index of twining fibre cladding.
8. micro-fluidic optical fiber biosensor according to claim 7 is characterized in that said light source is laser instrument or fluorescence light source.
9. the method for preparing the described micro-fluidic optical fiber biosensor of claim 1 is characterized in that comprising the steps:
(1) part with Transmission Fibers is drawn into diameter less than 10 μ m, and length is the fiber-optic filament of 1mm~10cm;
(2) fiber-optic filament that step (1) is obtained closely is wrapped on the outer wall capillaceous of diameter less than 2mm, then at the high-reflecting film that twines position plating one deck exciting light and flashlight;
The optically-coupled of (3) light source being sent gets into an end of Transmission Fibers, and the other end of Transmission Fibers is connected with signal processing apparatus;
(4) feed in the kapillary and be with fluorescently-labeled biological specimen.
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CN101813629B (en) * 2010-04-29 2011-09-28 大连海事大学 Photonic crystal fiber chemical/biological sensing head and preparation method thereof
CN104181134B (en) * 2014-07-30 2016-08-17 深圳市开天源自动化工程有限公司 Fluorescence detection device
CN106706565B (en) * 2016-12-23 2019-11-19 暨南大学 A kind of spiral light microfluidic sensor
CN107219192B (en) * 2017-06-12 2019-08-09 东北大学 It is a kind of based on the biomolecule of photonic crystal fiber in fine detection system
CN107796795B (en) * 2017-10-13 2019-08-09 福州大学 Fluorescent optical sensor for gas detection
CN108896539A (en) * 2018-05-15 2018-11-27 武汉大学 Measure the optofluidic detector of phosphorus content in seawater
CN108489902B (en) * 2018-05-17 2020-09-25 电子科技大学 High-repeatability optical fiber laser micro-flow detector and detection method
CN112052556B (en) * 2020-07-28 2021-06-04 华南理工大学 Formula design method of broadband laser glass
CN112525865B (en) * 2020-11-17 2022-12-27 西安工业大学 Hemolysis detection optical fiber micro-fluidic sensing system and detection method
CN113097840A (en) * 2021-03-11 2021-07-09 江苏师范大学 Efficient guided wave biconical single crystal fiber gain module and installation method thereof

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