CN107754914A - Cheap controller used in syphilis diagnosis micro fluidic device based on new liquid stream driving principle - Google Patents

Cheap controller used in syphilis diagnosis micro fluidic device based on new liquid stream driving principle Download PDF

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CN107754914A
CN107754914A CN201610728073.1A CN201610728073A CN107754914A CN 107754914 A CN107754914 A CN 107754914A CN 201610728073 A CN201610728073 A CN 201610728073A CN 107754914 A CN107754914 A CN 107754914A
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micro
pipeline
substrate
fluidic chip
chip
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李榕生
葛宇杰
蒋剑萍
葛光奇
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    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502723—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by venting arrangements
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    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
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    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302—Apparatus specially adapted for immunological test procedures
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    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/536—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase
    • G—PHYSICS
    • G01—MEASURING; TESTING
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    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/571—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses for venereal disease, e.g. syphilis, gonorrhoea
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0631—Purification arrangements, e.g. solid phase extraction [SPE]
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    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/044—Connecting closures to device or container pierceable, e.g. films, membranes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0645—Electrodes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B01L2300/123—Flexible; Elastomeric
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/16—Surface properties and coatings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/16—Surface properties and coatings
    • B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
    • B01L2400/0439—Moving fluids with specific forces or mechanical means specific forces vibrational forces ultrasonic vibrations, vibrating piezo elements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants

Abstract

The present invention relates to a kind of cheap controller used in syphilis diagnosis micro fluidic device based on new liquid stream driving principle, belong to analysis testing field.With dimethyl silicone polymer i.e. PDMS that is cheap and easily processing to make controller used in syphilis diagnosis with the substrate of micro-fluidic chip be a technical goal；But some intractable problems be present.This case main points are, micron silica granule filler is filled up in its pipeline of the chip, its function of the filler includes supporting pipeline inwall, and, with the set of hydrophily fluid channel come the hydrophobic pipeline of compensatory script, and, extruding, cover inner-walls of duct face and thereby reduce the chance that large biological molecule contacts with the internal face, the chip terminal attaches installing miniature ultrasonic transducer units, ultrasonic intensity rapid decrement in short distance is reached to the strong absorption of ultrasonic wave using PDMS, thereby in the both ends induced synthesis interfacial tension difference of the chip, and then sample liquid stream is facilitated to be flowed along its pipeline of chip to the terminal direction.

Description

Cheap controller used in syphilis diagnosis micro fluidic device based on new liquid stream driving principle
Technical field
The present invention relates to a kind of cheap controller used in syphilis diagnosis micro fluidic device based on new liquid stream driving principle, the miniflow Control device is to belong to analysis testing field based on antigen/antibody specific reaction come the special purpose device of Diagnosis of Syphilis antigen.
Background technology
The micro-fluidic controller used in syphilis diagnosis technical background of associated multi-channel, may refer to the patents of invention such as CN 200910152141.4 Application case.
Only for the microflow control technique overall general picture of itself, famous micro-fluidic expert Mr. Lin Ping Cheng may refer to not The monograph " diagram Microfluid based Lab on a chip " gone out before long, the monograph is published via Science Press, and the monograph is to micro-fluidic Past of technology, now, and, vision of the future etc. etc., suffer from detail, be deep into long discussion of detail.
So, the Important Problems of this case that to have a talk below concern.
The basic framework of micro-fluidic chip, including it is etched with the substrate of conduit and the cover plate to fit together therewith, institute State the fluid course on substrate, before upper cover plate is assembled, it is apparent on see to be exactly some conduits, wait until lid is covered thereon After piece, just really closure forms the fluid course, and the conduit inner surface of the conduit is together with the part that surround the conduit Cover plate forms described fluid course together；So, it is clear that assemble the fluid course after completing, its inner surface face Long-pending major part is the inner surface area of that conduit, and in other words, the state or property of the conduit inner surface are substantially determined The integrality or property of the fluid course are determined；Therefore say, the inner surface state or interior of this conduit of the structure on substrate Surface nature is key factor；In principle, any material that can be kept or keep its solid forms substantially, can be used To make substrate and cover plate, such as, the material that can act as substrate and cover plate can be monocrystalline silicon piece, quartz plate, sheet glass, height Polymers such as dimethyl silicone polymer, polymethyl methacrylate, makrolon etc.；Certainly, the selection of substrate and the choosing of cover plate Material be able to can also be differed with identical；From the point of view of material consumption, manufacture difficulty and application popularization prospect etc. etc., these Not small difference, the especially selection of that substrate between material be present, have a great influence.
In various substrate making materials, dimethyl silicone polymer, i.e. PDMS, comparatively very easily shaping, at this It is extremely simple that conduit is made on the substrate of sample, and the lower cost for material, substrate is made with the polydimethyl siloxane material, Conduit is being suppressed or etched thereon, and is being engaged with the cover plate that the cheap material such as glass or polypropylene or other plastic sheets makes, It is a kind of more satisfactory selection seemingly；Certainly, patch material can also select to use cheap polydimethyl siloxane material： So, this substrate selection is the scheme of polydimethyl siloxane material, and material is extremely cheap, and making is extremely simple, seems and should also be as It is extremely easy to popularize, promotes.
But thing is really not so simple.
First, this polydimethyl siloxane material, that is, the material that alphabetical PDMS is referred to of abridging, itself are a kind of strong Strong hydrophobic material, conduit is built on this material, if without being operated for the modified of the conduit surface, then, it is whole After body assembling is completed, that is, after covering cover plate, because the conduit its inner surface in structure occupies most fluid course Inner surface, then, its strong hydrophobic property of the PDMS conduits inner surface, is deciding factor, it can be similar to water The fine liquid stream of polar liquid of solution by becoming very difficult, its flow resistance is big, or even in general Micropump is all difficult to Promote, certainly, if cover plate also selects to use the PDMS material, then, problem is substantially identical, similar；Therefore, existing Among having technology, modification is modified particular for the conduit inner surface on the PDMS material, is necessary operation；So, this The individual modified operation for PDMS conduit inner surfaces is pretty troublesomeThat falls nor this problem, forms serious technical puzzlement, It is another problem：PDMS polymer molecules inside its body phase of this PDMS material substrate have to be diffused to the surface, moves automatically The characteristic of shifting, the characteristic that this substrate body phase inside PDMS polymer molecules are diffused to the surface, migrated automatically, will cause by table State after the modification of its inner surface of that conduit of face modifying and decorating can not maintain the sufficiently long time, and that is through surface Holding time for conduit its inner surface state after modification is substantially only sufficient to the time needs for completing laboratory internal test experiments； In other words, by surface is modified or the PDMS conduit inner surfaces of surface modification, after it is modified or institute's shape after modification is said Into surface state can not be lasting, but soon automatically tend to or say become again surface be modified before surface state, compared with The strong hydrophobic surface state of that script is returned in the short time, then, just think, such micro-fluidic chip can be big Amount making, mass storage, it is widely popularized, answer is it is obvious that is, impossible.Conduit on this PDMS material, does not do If surface modification, it can not pump and pass through similar to the fine liquid stream of polar solvent of the aqueous solution, chip also cannot just use；And such as Fruit has been cooked surface modification, can not persistently keep its state after modifying again, or equally can not popularization and application.
According to the literature, there is a kind of expedient solution, be that a small amount of surface-active is added in sample to be tested solution Agent, so as to which during test, dynamic, temporary transient effective surface hydrophilic layer is built temporarily in the PDMS conduits inner surface； However, due to the amphipathic characteristic of surfactant, the introduced surfactant of the program is inevitable simultaneously also can be with sample solution In tested composition occur combination so that tested composition can not be detected normally or it is detected ratio and dubiously dropped It is low；The surfactant is possibly even fully wrapped around by tested composition with micelle form so that tested composition can not be detected or Identification；Therefore, this kind adds the scheme of surfactant into sample solution, is far from a preferable solution.
So, how to accomplish that substrate can either be made using cheap PDMS material, and the conduit can be released Inner surface decorating state can not persistently, chip can not largely make, largely lay in and then be widely popularized and such a make this area The puzzlement that numerous professionals are entangled with for a long time, the highly difficult problem that exactly one its obvious technology barrier can not despise.
Be present many year in the highly difficult problem, so far, not yet properly settled.
Second, the PDMS material of non-surface modification, it is stated that, its surface is strongly hydrophobic above, this strong hydrophobic Material surface and also have another problem, that is, this strong hydrophobic PDMS surfaces can adsorb large biological molecule, and And these adsorbed large biological molecules can also further depression further on PDMS surfaces, gradually fall into it is gradually deep, until It is heavy to be trapped within the body phase of PDMS substrates, in fact, this process, partly it is also due to PDMS material body phase interior polymer Molecule, which has, to be diffused to the surface, caused by travel motion；Such case, it can also be explained from another angle, i.e. continue not Disconnectedly from inside PDMS body phases to those polymer molecules of its diffusion into the surface, migration, its result moved, be little by little by that It has been involved in a bit by the large biological molecule of adsorption within the body phase of PDMS substrates, briefly, these adsorbed biologies Macromolecular is exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up the phenomenon of large biological molecule, its institute Caused by influence, necessarily cause the severe deviations of all kinds of test data of experiment for being related to large biological molecule.
As described above, the problem of PDMS substrates, is, its not only adsorption large biological molecule, and swallow up biological big point Son, so, as the large biological molecule of experiment test object, its disappearance will not stop because surface saturation is adsorbed, and It is, it is constantly adsorbed, also constantly swallowed up.
On PDMS substrates, its body phase is constantly swallowed up and tests showing for associated biomolecule macromolecular in related experiment test process As, it is to say that another kind, which is explained, substantial amounts of Minute pores in PDMS body phases be present, associated biomolecule macromolecular by after adsorption, Depression enters these Minute pores, and then is swallowed up；However, inventor thinks, those can allow the sky of miniature scale Qi leel squeezes into the Minute pores therebetween, not equal to saying that they also can directly allow the large biological molecule of relative large scale to enter Enter, both difference on yardstick are huge, must not make sweeping generalizations.Explanation is bypassed, in any case, as dependence test analysis object Large biological molecule is adsorbed by PDMS substrate conduits inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is known objective Existing phenomenon.
, can be from containment PDMS surfaces pair in order to prevent swallow up effect of this PDMS substrate bodies relative to large biological molecule The absorption of large biological molecule addresses, and method is chemically modified modification aiming at the PDMS material surface, for For PDMS is the situation of substrate material, modification exactly is chemically modified to the surface of described channel portion, by chemistry The conduit inner surface of modification, can contain its absorption to large biological molecule, and then avoid large biological molecule quilt PDMS substrate body phases are swallowed up；But or that old problem, that is, the chemical modification on PDMS material surface is modified it Surface state afterwards can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface, migrate automatically Process, can soon by that by surface chemical modification be modified conduit inner surface state become again script it is strong it is hydrophobic simultaneously And the state of strong adsorption large biological molecule, in other words, no matter how professionals in the field turn from side to side, the PDMS substrates its Conduit inner surface is always rapidly to strong hydrophobic surface state evolution.
So, how can either obtain that PDMS material price is extremely cheap, substrate makes extremely easy benefit, and can is enough Reach and contain the absorption process of the PDMS substrate conduit inner surfaces to large biological molecule for a long time, and then prevent PDMS substrate bodies relative The effect of swallowing up of large biological molecule so that related chip manufactured goods are able to maintain that a prolonged enough, rational shelf-life, It is exactly a very intractable problem.The problem equally makes this area numerous specially as another problem addressed above Industry personnel are entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise.Should Also be present many year in problem, so far, also not yet properly settled.
Third, the polydimethyl siloxane material, namely PDMS material, the active force very little wherein between polymer molecule, The polymer molecule of low polymerization degree inside its body phase is in constantly into the dynamic process of surface migration, therefore, includes PDMS After it has been formed, the surface topography in its inner-walls of duct face of chip can be because of described low polymerization degree polymer point for the chip of substrate material Son moves about, pours into the surface and change, and the change of its pattern is somewhat similarly to Rheological Deformation, trickling deformation or creep and become Pattern caused by shape institute is possible changes；In the higher PDMS material of some low polymerization degree component ratios, this kind somewhat similar Can be showed in the phenomenon of Rheological Deformation, trickling deformation or the deformation of creep must be than more significant；This kind include PDMS substrates chip its The dynamic of inner-walls of duct surface topography after shaping changes property, namely the described property or stream that are somewhat similarly to Rheological Deformation Dropping down the property of deformation or the property of the deformation of creep, the word of rheology one is applied mechanically in this case, integration, also referred to as the rheological equationm of state or rheology become Shape property, the dynamic of corresponding inner-walls of duct face pattern change, and this case is also referred to as rheology；As described above, because of this kind of material Expect certain Rheological Deformation property as described above that its own has, its manufactured goods actually can at leisure Rheological Deformation and cause The manufactured goods total form generation changes；Influence caused by its Rheological Deformation property, it is to be not easy to feel in terms of macroscopic perspective Examine, still, for the very fine micro-fluidic chip of its internal structure, the rheological equationm of state can but cause bigger shadow Ring, the fluid course namely the pipeline therefore, during pre-production formed, because the wall of its tube chamber of pipeline is main It is the wall of PDMS materials, so, the cross-sectional area of the pipeline actually can gradually become because of rheology over time It is small, stated differently, since the reason for the rheology, the natively finer pipeline that is flowed through for liquid sample Its tube chamber the more can become the more narrow, in the case of flow time is sufficiently long, or even the pipeline tube chamber can partly close or all Ground closes, and then make it that sample fluid course is thoroughly blocked, and closes with being even also not reaching to its luminal part of pipeline The degree closed or fully closed, its fluid passage that can be provided of that pipeline narrow because of rheology, then, in pipeline Its inner surface originally be exactly strongly it is hydrophobic in the case of, aqueous sample liquid is just more difficult to by becoming more so because of rheology Narrow micro-channel, then, the influence of substrate rheology how is resisted, maintains the basic framework of the pipeline not occur seriously to become for a long time The problem of shape, also, keep the long-term unobstructed of the pipeline is exactly a urgent need to resolve.
The content of the invention
The technical problem to be solved by the invention is to provide a package solution, solves totally above A series of problems addressed, also, the solution is applied to controller used in syphilis diagnosis multichannel micro-fluidic chip field, form one The new controller used in syphilis diagnosis multichannel micro-fluidic device of kind.
The present invention solves the technical problem by following scheme, and the device that the program provides is that one kind is based on new liquid stream The cheap controller used in syphilis diagnosis micro fluidic device of driving principle, the structure of the micro fluidic device include multichannel micro-fluidic chip, The structure of the micro-fluidic chip includes being bonded to each other the substrate and cover plate of installing together, and the substrate and cover plate are plate object Or the channel structure via mould pressing process or etching technics formation is contained in tablet, that face towards the cover plate of the substrate, The substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or simply punch work The window structure that skill is formed, be bonded to each other the substrate that is installed together and the cover plate be built into jointly containing pipeline configuration with And the micro-fluidic chip for the liquid pool structure being attached thereto, the locations of structures of the pipeline are located at what the substrate was bonded to each other with the cover plate Interface zone, its side of the window is blocked by the cover plate and opposite side opens, and the locations of structures of the window is exactly the liquid pool Locations of structures, the quantity of the liquid pool is three, and its locations of structures of two liquid pools therein is located at the sample introduction of the micro-fluidic chip End, its locations of structures of a remaining liquid pool are located at the end of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested End, the terminal are located remotely from each other with the sample introduction end, and one end of the pipeline is via the discrimination for being similarly positioned in the interface zone being bonded to each other Tubulose turnout respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline with positioned at the micro-fluidic chip institute A remaining liquid pool UNICOM for terminal is stated, and, sequentially it is respectively installed in the working electrode on diverse location in the pipeline And to electrode and reference electrode, the working electrode is by conductive electrode and the embedding being attached on the conductive electrode The gold size sensitive membrane of syphilis specific antibody is formed, and the construction of the pipeline is in parallel construction, the pipeline in parallel construction It is made up of four lateral parallel connections, the quantity of the working electrode is four, the installation position difference of four working electrodes In four laterals, and, the specific antibody in its top layer gold size sensitivity membrane structure of four working electrodes It is the four kinds of syphilis antibody materials that can be specifically bound to Treponema pallidum antigen respectively, four kinds of antibody materials are syphilis specific respectively Antibody TP0684, TP0453, TP0821 and TP0319, its material of the working electrode are gold material or thermal decomposition conductive polymer Sheet or thread is presented in sub- material, its pattern of the working electrode, and emphasis is that its material of the substrate is dimethyl silicone polymer material Matter, its surface of the substrate are the surfaces of primary form, the surface of the primary form its be intended to refer to and do not pass through any surface The surface of the primary form of the material of chemical modification or any surface chemical modification, the structure of the micro fluidic device is also including micro- Type ultrasonic transducer, and, higher-order of oscillation electric signal transmission cable, one end of the higher-order of oscillation electric signal transmission cable is with being somebody's turn to do Miniature ultrasonic transducer units link together, the miniature ultrasonic transducer units attach be installed in the micro-fluidic chip cover plate or The position of the neighbouring terminal of substrate；Its major function of the miniature ultrasonic transducer units is surveyed in the actual sample introduction of micro-fluidic chip During examination, using the sample introduction end and the distance between the terminal and the miniature ultrasonic transducer units installation position difference and Difference on its ultrasonic intensity experienced, its interfacial tension of sample introduction end described in induced synthesis and its interface of the terminal Difference between power, the interfacial tension difference between the micro-fluidic chip both ends can be between the both ends of the micro-fluidic chip Pressure gap is formed, the pressure gap can drive sample solution to the end flow；The poly dimethyl that is soft and having elasticity Its function of the substrate of siloxanes material includes, with its property to the strong absorption of ultrasonic wave, absorbing ultrasonic wave strongly, and Thereby the quick of ultrasonic intensity is realized within micro-fluidic chip terminal to the limited short distance between the sample introduction end Successively decrease；And many silica dioxide granules, many silica dioxide granules are filled in the pipeline, the pipeline its Tube chamber is filled up by many silica dioxide granules, and its particle size range of the silica dioxide granule is between 10 microns and 200 microns Between, the silica dioxide granule is silica crystalline particles, silica glass granule or silica composition its shared weight Inorganic glass particles of the percentage more than 80% are measured, a remaining liquid pool is also referred to as terminal liquid pool, in the terminal liquid pool Filled with some high hydroscopic resin particles, its opening end of the terminal liquid pool is covered by breathable microporous film.
Only for the word of high hydroscopic resin one art-recognized meanings of itself, come for the professional of chemical field Say, be known.
The high hydroscopic resin is commercially available.
Only for the word of breathable microporous film one art-recognized meanings of itself, for the professional of technical field of membrane, It is known.
The breathable microporous film is commercially available.
Its particle diameter of the silica dioxide granule can be that the basis between 10 microns and 200 microns is actually needed and any The particle diameter specified, such as 10 microns, 30 microns, 70 microns, 100 microns, 150 microns or 200 microns of the particle diameter, etc..
The scope of further preferred its particle diameter of the silica dioxide granule is between 100 microns and 200 microns.
Its pattern of the silica dioxide granule is unlimited, and the silica dioxide granule for example can be spheric granules, rod-shaped particles, length Cube shape particle or any amorphous granular.
The various silica dioxide granules manufacturing technology of itself is known technology.
Various forms, the silica dioxide granule market of all size are on sale.
The silica dioxide granule can also customize to specialized factory.
The preferred scope of its internal diameter of pipeline is between 500 microns and 1000 microns；It is but excellent compared to above-mentioned The internal diameter of the pipeline scope of choosing, more tiny internal diameter of the pipeline or thicker internal diameter of the pipeline are also what this case was allowed.
The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and syphilis specific antibody-solutions uniformly, is used a little Sample instrument point sample is coated on specified structure position, and forms its drying and forming-film.Syphilis specific in the gold size sensitive membrane Antibody is the syphilis antibody of horseradish peroxidase or glucose oxidase mark, and the gold size sensitive membrane has been included as solid Determine above-mentioned each syphilis specific antibody and introduce complementary medium therein, the complementary medium such as chitosan, acetic acid are fine Dimension is plain, gelatin is therein a kind of or their mixture.
The pipeline and the lateral and the manifold shape turnout in the microfluidic chip structure, in it Footpath size may each be arbitrarily selected size, still, for as far as possible less with prepare liquid sample and reduction reagent loss etc. Consideration, the pipeline and the lateral and the manifold shape turnout preferably select capillary level passage, institute The passage for stating capillary level implies that its internal diameter passage suitable with the internal diameter of the capillary on ordinary meaning.The capillary is in it The shape of cross section of portion's passage can be arbitrary shape, and the shape of cross section is for example circular, oval, square, rectangle, bar Shape, naturally it is also possible to it is the linear of bending arbitrarily be present, also, the interior shape of the capillary is with the extension of pipeline, The shape of cross section of different parts can also allow to be different shapes.Only for the word of capillary one, its art-recognized meanings is public Know.
What is be related in structure is the electrode of microsize to electrode and reference electrode, and its electrode shape, which may each be, appoints The selected shape of meaning, the arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..It is described Art-recognized meanings to electrode and the reference electrode vocabulary of itself are known.
It is related to several liquid pools in this case microfluidic chip structure, the liquid pool is the pond shape or capsule for transitional liquid storage Shape constructs, and its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, and the cavity shape is for example round Cylindrical cavity shape, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..The size of the liquid pool can be any Selected size, still, in order to as far as possible less with prepare liquid sample and reduce reagent loss, the liquid pool be preferably capable of with The liquid pool of the microminiature of capillary matching.
Only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field, It is known.
Various sizes, variously-shaped ultrasonic transducer are commercially available；Its size of commercially available miniature ultrasonic transducer units It may diminish to the magnitude only calculated with millimeter.
Only with regard to miniature ultrasonic transducer units its technique for fixing on general industry application solid body surface its It is known general technology for the professional in ultrasonic technology field for body.This case is not to this expansion superfluous words.
Only with regard to naked PDMS substrates itself conduit molding or lithographic technique for, be open-and-shut known technology； Similarly, the technology of hole-opening is even more known simple technique on naked PDMS substrates.This case is not also to this expansion superfluous words.
The industrial products market of involved its all size of higher-order of oscillation electric signal transmission cable is on sale.
The structure of the micro fluidic device can also include higher-order of oscillation electric signal generator；The higher-order of oscillation electric signal passes Its other end of transmission cable can be connected with the higher-order of oscillation electric signal generator.
The involved higher-order of oscillation electric signal generator technology of itself, come for the professional in ultrasonic technology field Say, be simple and known；The higher-order of oscillation electric signal generator can customize to ultrasonic instrument specialized factory.
The preferred scope of its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 2 milliwatts and 2000 milliwatts Between；The preferred scope of the frequency of its ultrasonic wave operationally launched of the miniature ultrasonic transducer units be between 100KHz with Between 12MHz.
This case device can further include some annexes certainly, and the annex is such as multiple tracks electrochemical workstation Deng the art-recognized meanings of the multiple tracks electrochemical workstation are known.The each work being related in this case microfluidic chip structure Electrode and to electrode and reference electrode etc., special it can get lines crossed and the multiple tracks electrochemical workstation via corresponding respectively The corresponding interface coupled.It is described that special to get lines crossed be for by each phase of each electrode and the multiple tracks electrochemical workstation Answer the private cable that interface is coupled to each other.The micro-fluidic chip in this case device, its structure can also include micro-valve, The quantity of the micro-valve is unlimited, and according to being actually needed, the micro-valve can be installed in any need in the microfluidic chip structure Position to be mounted；The word of micro-valve one is for the professional of micro fluidic chip technical field, the art-recognized meanings of itself It is known；The micro-valve itself manufacturing technology and the use of technology is also known；The component that the micro-valve is not required.
The diameter of the working electrode can allow to be that any setting is easily installed the suitable diameter used, still, It is recommending or say preferable its scope of the diameter between 0.1 micron to 2000 microns；The length of the working electrode can To allow to be that any setting is easily installed the length used, it is however recommended to or to say the preferable length its scope be 1 Micron is between 15000 microns.
It is installed in by spraying or point sample instrument point sample or the coating of other appropriate process described in the working electrode surface layer Gold size sensitive membrane, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness, It is however recommended to thickness preferable thickness is between 10 nanometers and 200 nanometers in other words.
The cover plate in chip structure, its material can allow to be any electrical insulating property material, such as：Polypropylene, Glass, polymethyl methacrylate, dimethyl silicone polymer, etc., in order to make smaller size of micro-fluidic chip, for example do Into the micro-fluidic chip of only 2.0 centimetres to 3.0 centimetres of super-small of length, and realized in the extremely short distance to ultrasonic wave Extremely fast decay, can preferably dimethyl silicone polymer be used as cover plate.Certainly, selected on large-sized micro-fluidic chip Using dimethyl silicone polymer it is used as the cover plate, and this case technical scheme is allowed.
Positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal should Air line distance between a remaining liquid pool can be arbitrarily selected suitable distance, still, the distance as needed Preferred value is between 3 centimetres and 7 centimetres.
Described its thickness of cover plate and substrate can allow be any setting the thickness for being easy to assembling, the thickness of recommendation or say Preferable thickness is between 1.0 millimeters and 5.0 millimeters.Less thickness is advantageous to save material.
The application method of this case micro-fluidic chip：
Itd is proposed first based on this case and the first public new liquid stream driving principle, its application of this case micro-fluidic chip are transported Among work, the new liquid stream driving method is determined completely without involving any additional Micropump.
The interfacial tension difference that this case is formed between micro-fluidic chip both ends caused by the ultrasonic wave, Driving liquid stream flows in the capillary channel of the four-way micro-fluidic chip, right respectively using four-way electrochemical analytical instrument Four kinds of controller used in syphilis diagnosis antigens are detected.
The specific detection of this case micro-fluidic chip is as follows using step：
1st, blood serum sample liquid is added in micro-pipe road, under ultrasonic wave driving, various Treponema pallidum antigen molecules are by each logical In road on electrode surface gold size sensitive membrane embed corresponding horseradish peroxidase-labeled syphilis specific antibody capture.
2nd, the syphilis specific antibody of horseradish peroxidase-labeled is formed immune multiple with the Treponema pallidum antigen in blood serum sample Compound.
3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, it is above-mentioned using amperometric detection Curent change caused by reaction, it is derived from the species and content of various analytes.
4th, result is subjected to comprehensive analysis, comprehensive diagnos is carried out to Treponema pallidum antigen.
It is an advantage of the invention that its close position installs miniature ultrasonic with attaching in the terminal of the micro-fluidic chip Wave transducer, with the ultrasonic wave of miniature ultrasonic transducer units transmitting low-power, high-frequency band, meanwhile, utilize poly dimethyl silicon Its strong absorbability to ultrasonic wave of oxyalkyl piece, in shorter distance, it is, from the terminal to the sample introduction In the very short distance of only several centimeters yardsticks between end, reach the rapid decrement of ultrasonic intensity, thereby in the micro-fluidic core The difference of the interfacial tension is caused at the both ends of piece, and then, utilize its shape of the difference of the interfacial tension between the both ends Into the both ends between pressure gap, driving sample liquid stream in the pipeline to the terminal direction flow.By this case Liquid stream drive scheme, the equipment of traditional Micropump etc is altogether dispensed with；The micro-fluidic chip of Micropump is eliminated, it is tied Structure is more succinct, and its production process is less, and its cost of manufacture is lower, and this kind of succinct structure is more beneficial for reaching the low of micro-fluidic chip Cost application.
Its scheme of this case and by the pipeline except electrode installation take up space in addition to all clearance spaces whole Filled up with the silica dioxide granule.Those are filled in the silica dioxide granule in pipeline, and this case is to its overall abbreviation titanium dioxide Silicon grain filler, its function include support, withstand the tube chamber of the pipeline its inwall so that the tube chamber of the pipeline is from because of institute State rheology and narrow, prevent its reduced cross-sectional area of the tube chamber of the pipeline or even close, so as to maintain the base of the pipeline for a long time Serious deformation does not occur for this framework.
Numerous silica dioxide granule entities are mutually banked up under this case framework together at random in the pipeline, the titanium dioxide The function of silicon grain filler, also include certainly with the hydrophilic surface of its silica dioxide granule, utilize each adjacent titanium dioxide Mutual formed complications are continuous and its inner surface that is mutually close together by water-wetted surface of silicon grain has hydrophilic The space of property, in the hydrophilic fluid channel of the pipeline Inner Constitution network morphology, although this complications can be continuous All the time the fluid channel with hydrophilic nmature, then, inside the tube chamber of the pipeline simultaneously and a plurality of miniflow deposited The effect of its synthesis of road, integrated, cumulative superposition in other words, is the equal of the relatively fine hydrophilic capillary of caliber Passage；Its presence of the continuous hydrophilic fluid channel of the complications, the PDMS of the primary form is counteracted to a large extent The flow resistance for liquid sample caused by the strong hydrophobic property in its surface of substrate；In other words, because of liquid sample, it is accounted for The composition of maximum ratio is water, and liquid sample is substantially exactly the aqueous solution, therefore, the presence of the silica dioxide granule filler, Can significantly overcome with the unmodified PDMS substrates of hydrophobic property and surface its to the aqueous solution it is incompatible, repel and Barrier effect, so be greatly reduced belong to properties of Aqueous Solution sample liquid stream its be advanced through the resistance of pipeline.
Under this case framework, inside the tube chamber of the pipeline, the area of its lumen wall wall of former pipeline, because of described two The rigid of silicon oxide particle filler ties up, the table of part hydrophobic property that still can also be exposed on lumen wall wall Its area of face is already dramatically reduced, and the area on its still exposed part surface for belonging to hydrophobic property is much Less than the wall surface area of the hydrophobic property of the lumen wall wall in the presence of no silica dioxide granule filler； So, under this case framework, in its lumen of the pipeline, its remaining hydrophobic surface increases surface newly with hydrophilic part, and it is folded Adding, comprehensive, summation, cumulative technique effect, is to form the surface for tending to be hydrophilic on the whole；In other words, in institute State inside the tube chamber of pipeline, its interfacial tension between sample solution of the part surface of remaining hydrophobic property, plus parent The part of aqueous nature increases its interfacial tension between sample solution of surface newly, that it is superimposed, comprehensive, summation, cumulative Technique effect, be so that its solid-liquid interfacial tension inside the tube chamber of the pipeline synergy level off to capillary glass tube its Interfacial tension between tube chamber inner surface and sample solution.
Therefore, exist in the pipeline under this case framework for having stated silica dioxide granule filler, while rely on this Case sample liquid stream drive scheme, it becomes possible to the driving to sample liquid stream is reached with relatively low ultrasonic power, with this case mechanism The test liquid is driven to flow to the end flow.
On the other hand, due to its rheological equationms of state of the PDMS as substrate material, it is filled in the pipeline The interior silica dioxide granule filler, can gradually by constantly Rheological Deformation and to arest neighbors free space promote PDMS The pipeline wall of material more tightly wraps up, and this process eventually causes those part two for pressing close to the lumen wall wall Silicon oxide particle is stuck in original place or is stuck in original place or embedding in-situ silica dioxide granule and its embedded in original place, the part Incarceration is together, described due to this reason each other for the remaining silica dioxide granule banked up with being mutually closely packed together Silica dioxide granule filler just will not move in the pipeline easily, silica dioxide granule therein be also substantially all by Original place is locked in, therefore the stream framework of the micro-fluidic chip can be kept for a long time.
The particle size range of its particle of this case silica dioxide granule filler between 10 microns and 200 microns, compared to For general organic molecule, general large biological molecule, the particle diameter of its particle of this case silica dioxide granule filler can be rated as huge Greatly, due to its huge particle diameter, and the inner surface of the surface of its polarity and the pipeline of strong hydrophobic PDMS materials can not Mutually perhaps say and mutually melt, then, the huge silica dioxide granule of this kind of particle diameter can not be by the pipeline of PDMS materials Surface is adsorbed, and can not more be swallowed up by the inner surface of the pipeline of PDMS materials, the huge titanium dioxide of this kind of particle diameter Silicon grain surely not be fully sunk in easily or sink to completely PDMS materials its among intrinsic many Minute pores, and Because above it is stated that the rheology the reason for, the silica dioxide granule filler can be stuck in original place in other words it is embedding In original place without moving easily.
Inside the tube chamber of the pipeline, its lumen wall wall of former pipeline is entirely the surface of hydrophobic property originally, such as Upper described, under this case framework, rigid because of the silica dioxide granule filler ties up, on lumen wall wall still also Its area of the surface of part hydrophobic property that can be exposed is already dramatically reduced, and it is still exposed to belong to hydrophobicity The area on the part surface of matter has been far smaller than the tube chamber in the presence of no silica dioxide granule filler The wall surface area of the hydrophobic property of inwall wall；The reason for because of the rheology, it is close to those dioxies of lumen wall wall Silicon carbide particle, little by little it is partially embedded into or is partly absorbed among the lumen wall wall, the dioxy among the state Silicon carbide particle its towards the part surface of lumen wall wall with have occurred and that matching deformation the lumen wall wall it is tight Closely connected conjunction, then, the matching is deformed and closely pasted with silica particles having occurred and that in lumen wall wall The part wall of conjunction actually can not contact with flowing through the sample solution of pipeline, that is to say, that the wall of this part is Through suction-operated can not be produced to the large biological molecule therein that flows through the sample solution of pipeline and organic molecule.Based on above-mentioned Mechanism, then because fill up the pipeline the silica dioxide granule filler its presence, its lumen wall wall of the pipeline The overwhelming majority in face is tightly covered, and these described walls tightly covered can not be with flowing through the pipeline Sample solution contact, only remaining fraction be not brought into close contact by its surface of silica dioxide granule, tightly cover Hydrophobic surface may be contacted with sample solution, in other words, under this case framework, large biological molecule in sample solution and have Its direct touch opportunity with hydrophobic PDMS walls of machine molecule is significantly reduced, thus, the lumen wall faces of PDMS materials its The adsorptive hindrance and interference of swallowing up of large biological molecule and organic molecule are greatly reduced；As described above, this case scheme Be advantageous to exclude or weaken the adsorptive hindrance and swallow up interference, be advantageous to be lifted the reliability of correlation analysis test data.
As described above, this case silica dioxide granule filler, its function actually includes being similar to being directed to PDMS materials Inner surface of pipeline carry out chemical modification effect, functioning as its this respect of this case is by the pipeline of the PDMS materials Surface by the surface modification of hydrophobic property into the surface of hydrophilic nmature, still, with general, usual PDMS surface chemical modifications Its hydrophilic chemical decorative layer retention time is short, hydrophilic effect can not keep situation prolonged enough different, particle described in this case Huge silica dioxide granule filler, its particle being stuck by rheology can not both be moved easily, its huge particle diameter Particle can not more be swallowed up easily by the inner-walls of duct of PDMS materials, and therefore, its from this respect is similar to surface chemical modification Technique effect on see, its technique effect of this case, be form it is permanent, can not erase, can not consume, not be corroded, not by Hydrophilic surface reforming layer swallowing up, being not dissolved, it is just comparable to one kind in its correlation table of PDMS base materials in effect The permanent hydrophilic modifying superficial layer built on face.
It is related that the technical scheme of this case has dissolved its application to dimethyl silicone polymer substrate addressed above totally A series of technical barriers.Based on this case scheme, the very cheap polydimethyl siloxane material of this kind is just possible in miniflow Control chip prepare, production, using etc. field play bigger effect.
Brief description of the drawings
Fig. 1 is the schematic diagram of this case micro fluidic device embodiment chip part construction, it is shown that this structure Depression angle under chip internal pipeline and the structural form of each electrode and each related liquid pool, do not depict in the figure described Miniature ultrasonic transducer units and other annexes.
Fig. 2 is its rough outside side view of this case micro fluidic device.
In figure, 1,2,10 be the different liquid pool of three installation positions respectively, and 3 be manifold shape turnout, and 4,7,11,14 are respectively Installation position is different but four laterals parallel with one another for forming UNICOM's structure in parallel, and 5 be its that be installed in lateral 4 The working electrode that specific antibody material in the gold size sensitivity membrane structure of top layer is syphilis specific antibody TP0684,6 be installing The specific antibody material in its top layer gold size sensitivity membrane structure in lateral 7 is syphilis specific antibody TP0453's Working electrode, 12 be that specific antibody material in its top layer gold size sensitivity membrane structure being installed in lateral 11 is syphilis Specific antibody TP0821 working electrode, 13 be the spy in its top layer gold size sensitivity membrane structure being installed in lateral 14 Heterogenetic antibody material is syphilis specific antibody TP0319 working electrode, and 8 be to electrode, and 9 be reference electrode, and 15 be poly- diformazan The substrate of radical siloxane material, 16 be cover plate, and 17 be higher-order of oscillation electric signal transmission cable, and 18 be miniature ultrasonic transducer units, 19 be the sample introduction end of the micro-fluidic chip, and 20 be the terminal of the micro-fluidic chip；Arrow sign in legend The micro-fluidic chip its in actual motion, by pressure at two ends difference drive, the flow direction of its sample liquid stream.
Embodiment
In this case that Fig. 1 and Fig. 2 are shown embodiment, the structure of the micro fluidic device includes multichannel micro-fluidic core Piece, the structure of the micro-fluidic chip include being bonded to each other the substrate 15 and cover plate 16 of installing together, the substrate 15 and cover plate 16 be plate object or tablet, and that face towards the cover plate 16 of the substrate 15 is contained via mould pressing process or etching technics The channel structure of formation, the substrate 15 also containing be connected with the channel structure and pierce the substrate via mould pressing process, quarter The window structure that etching technique or simple drilling technology are formed, is bonded to each other the substrate 15 being installed together and the cover plate 16 is common Be built into the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the liquid pool be liquid pool 1, liquid pool 2, Liquid pool 10, the locations of structures of the pipeline are located at the interface zone that the substrate 15 is bonded to each other with the cover plate 16, its side of the window Blocked and opposite side opening by the cover plate 16, the locations of structures of the window is exactly the liquid pool 1, liquid pool 2, the structure bit of liquid pool 10 Put, the quantity of the liquid pool is three, and two liquid pools therein are that liquid pool 1 and liquid pool 2 its locations of structures are located at the micro-fluidic core The sample introduction end 19 of piece, a remaining liquid pool be when liquid pool 10 its locations of structures is located at the micro-fluidic chip actual sample introduction test its The terminal 20 that liquid flows in chip, the terminal 20 is located remotely from each other with the sample introduction end 19, and one end of the pipeline is via being similarly positioned in The manifold shape turnout 3 of the interface zone being bonded to each other, should respectively with the liquid pool 1 positioned at sample introduction end 19 and the UNICOM of liquid pool 2 The other end of pipeline and a remaining liquid pool for the terminal 20 positioned at the micro-fluidic chip are the UNICOM of liquid pool 10, with And sequentially it is respectively installed in working electrode in the pipeline on diverse location and to electrode 8 and reference electrode 9, the work Make electrode by conductive electrode and the gold size sensitive membrane for having embedded syphilis specific antibody being attached on the conductive electrode Form, the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of four lateral parallel connections, the work The quantity for making electrode is four, and the installation position of four working electrodes is located in four laterals respectively, this four Working electrode is working electrode 5, working electrode 6, working electrode 12, working electrode 13 respectively, and, four working electrodes its Specific antibody in the gold size sensitivity membrane structure of top layer is the four kinds of syphilis antibody things that can be specifically bound to Treponema pallidum antigen respectively Matter, four kinds of antibody materials are syphilis specific antibody TP0684, TP0453, TP0821 and TP0319 respectively, are specifically deployed For, 5 be that specific antibody material in its top layer gold size sensitivity membrane structure being installed in lateral 4 is syphilis specific Antibody TP0684 working electrode, 6 be the specific antibody in its top layer gold size sensitivity membrane structure being installed in lateral 7 Material is syphilis specific antibody TP0453 working electrode, and 12 be its top layer gold size sensitive membrane being installed in lateral 11 The working electrode that specific antibody material in structure is syphilis specific antibody TP0821,13 are installed in lateral 14 Its top layer gold size sensitivity membrane structure in specific antibody material be syphilis specific antibody TP0319 working electrode, it is described Working electrode 5, working electrode 6, working electrode 12, working electrode 13 its material are gold material or thermal decomposition conducting polymer material Sheet or thread is presented in matter, the working electrode 5, working electrode 6, working electrode 12, working electrode 13 its pattern, and emphasis is, Its material of the substrate 15 is dimethyl silicone polymer material, and its surface of substrate 15 is the surface of primary form, the primary form Surface its be intended to refer to the primary shape of the not material by any surface chemical modification or any surface chemical modification The surface of state, the structure of the micro fluidic device also include miniature ultrasonic transducer units 18, and, higher-order of oscillation electric signal transmission electricity Cable 17, one end of the higher-order of oscillation electric signal transmission cable 17 link together with the miniature ultrasonic transducer units 18, and this is miniature Ultrasonic transducer 18 is installed in the position of the cover plate 16 of the micro-fluidic chip or the neighbouring terminal 20 of substrate 15 with attaching； Its major function of the miniature ultrasonic transducer units 18 be in the actual sample introduction test of micro-fluidic chip, using the sample introduction end 19 with And the distance between the terminal 20 and the installation position of miniature ultrasonic transducer units 18 difference and its ultrasound experienced Difference between difference in intensity of wave, its interfacial tension of sample introduction end 19 described in induced synthesis and the terminal 20 its interfacial tension Different, the micro-fluidic chip both ends are that the interfacial tension difference between sample introduction end 19 and terminal 20 being somebody's turn to do in the micro-fluidic chip Both ends are to form pressure gap between sample introduction end 19 and terminal 20, and the pressure gap can drive sample solution to the side of terminal 20 To flowing；It is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and include with it to the strong absorption of ultrasonic wave Property, ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic chip terminal to limited between the sample introduction end The rapid decrement of ultrasonic intensity is realized within short distance；And many silica dioxide granules, many silica Grain is filled in the pipeline, and its tube chamber of the pipeline is filled up by many silica dioxide granules, the silica dioxide granule For its particle size range between 10 microns and 200 microns, the silica dioxide granule is silica crystalline particles, silica glass Glass particle or silica composition its inorganic glass particles of shared percentage by weight more than 80%, a remaining liquid Pond is also referred to as terminal liquid pool, is filled with some high hydroscopic resin particles in the terminal liquid pool, and its opening end of the terminal liquid pool is breathed freely Microporous barrier is covered.
Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, its try The flow direction of sample liquid stream.
Miniature ultrasonic transducer units 18 and higher-order of oscillation electric signal transmission cable 17 are depicted without in Fig. 1；Also, Fig. 1 And the associate members such as the higher-order of oscillation electric signal generator and multiple tracks electrochemical workstation are depicted without in Fig. 2.
Involved miniature ultrasonic transducer units 18 are commercially available；It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal transmission cable 17 is commercially available；It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；It can also determine to relevant manufacturers System.
Each working electrode in this example structure and can be respectively via each special electricity to electrode and reference electrode Cable or say is being got lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as annex or saying interface connection of getting lines crossed.

Claims (10)

1. the cheap controller used in syphilis diagnosis micro fluidic device based on new liquid stream driving principle, the structure of the micro fluidic device include Multichannel micro-fluidic chip, the structure of the micro-fluidic chip include being bonded to each other the substrate and cover plate of installing together, the base Piece and cover plate are plate object or tablet, and that face towards the cover plate of the substrate is contained via mould pressing process or etching work Skill formed channel structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, quarter The window structure that etching technique or simple drilling technology are formed, is bonded to each other the substrate being installed together and is built jointly with the cover plate Into the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the locations of structures of the pipeline is located at the substrate The interface zone being bonded to each other with the cover plate, its side of the window is blocked by the cover plate and opposite side opens, the structure of the window Position is exactly the locations of structures of the liquid pool, and the quantity of the liquid pool is three, and its locations of structures of two liquid pools therein is located at The sample introduction end of the micro-fluidic chip, when its locations of structures of a remaining liquid pool is located at the test of the micro-fluidic chip actual sample introduction its The terminal that liquid flows in chip, the terminal are located remotely from each other with the sample introduction end, and one end of the pipeline is mutual via this is similarly positioned in The manifold shape turnout of the interface zone of fitting respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline and position In a remaining liquid pool UNICOM for the terminal of the micro-fluidic chip, and, sequentially it is respectively installed in the pipeline not With the working electrode on position and to electrode and reference electrode, the working electrode is by conductive electrode and is attached to this The gold size sensitive membrane for having embedded syphilis specific antibody on conductive electrode is formed, and the construction of the pipeline is in parallel construction, institute State and be made up of in the pipeline of parallel construction four lateral parallel connections, the quantity of the working electrode is four, this four work The installation position of electrode is located in four laterals respectively, and, its top layer gold size sensitive membrane of four working electrodes Specific antibody in structure is the four kinds of syphilis antibody materials that can be specifically bound to Treponema pallidum antigen respectively, four kinds of antibody things Matter is syphilis specific antibody TP0684, TP0453, TP0821 and TP0319 respectively, and its material of the working electrode is gold material Sheet or thread is presented in matter or thermal decomposition conducting polymer material, the working electrode its pattern, it is characterised in that the substrate its Material is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, its meaning of the surface of the primary form Refer to that this is micro- not by any surface chemical modification or the surface of the primary form of the material of any surface chemical modification The structure of flow control apparatus also includes miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, higher-order of oscillation electricity One end of signal transmission cable links together with the miniature ultrasonic transducer units, and the miniature ultrasonic transducer units attach ground installing The micro-fluidic chip cover plate or substrate the neighbouring terminal position；Its major function of the miniature ultrasonic transducer units is In the actual sample introduction test of micro-fluidic chip, installed using the sample introduction end and the terminal with the miniature ultrasonic transducer units Difference in the distance between position difference and its ultrasonic intensity experienced, its interface of sample introduction end described in induced synthesis Difference between tension force and the terminal its interfacial tension, the interfacial tension difference between the micro-fluidic chip both ends can be at this Pressure gap is formed between the both ends of micro-fluidic chip, the pressure gap can drive sample solution to the end flow；It is soft The substrate of the dimethyl silicone polymer material its function that is soft and having elasticity is included with its property to the strong absorption of ultrasonic wave, right Ultrasonic wave is absorbed strongly, and thereby within micro-fluidic chip terminal to the limited short distance between the sample introduction end Realize the rapid decrement of ultrasonic intensity；And many silica dioxide granules, many silica dioxide granules are filled in institute State in pipeline, its tube chamber of the pipeline is filled up by many silica dioxide granules, its particle size range of the silica dioxide granule Between 10 microns and 200 microns, the silica dioxide granule is silica crystalline particles, silica glass granule or two Its inorganic glass particles of shared percentage by weight more than 80% of silica composition, a remaining liquid pool are also referred to as terminal Liquid pool, some high hydroscopic resin particles are filled with the terminal liquid pool, its opening end of the terminal liquid pool is hidden by breathable microporous film Lid.
2. the cheap controller used in syphilis diagnosis micro fluidic device according to claim 1 based on new liquid stream driving principle, its It is characterised by, the pipeline and the lateral and the manifold shape turnout are capillary channel.
3. the cheap controller used in syphilis diagnosis micro fluidic device according to claim 1 based on new liquid stream driving principle, its It is characterised by, the thermal decomposition conducting polymer is the electric conductivity formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated Material.
4. the cheap controller used in syphilis diagnosis micro fluidic device according to claim 1 based on new liquid stream driving principle, its Be characterised by, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the working electrode Length between 1 micron to 15000 microns.
5. the cheap controller used in syphilis diagnosis micro fluidic device according to claim 1 based on new liquid stream driving principle, its It is characterised by, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. the cheap controller used in syphilis diagnosis micro fluidic device according to claim 1 based on new liquid stream driving principle, its It is characterised by, the cover plate its material in structure is dimethyl silicone polymer material.
7. the cheap controller used in syphilis diagnosis micro fluidic device according to claim 1 based on new liquid stream driving principle, its Be characterised by, positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal should Air line distance between a remaining liquid pool is between 3 centimetres and 7 centimetres；Described its thickness of cover plate and substrate in structure Between 1.0 millimeters and 5.0 millimeters.
8. the cheap controller used in syphilis diagnosis micro fluidic device according to claim 1 based on new liquid stream driving principle, its It is characterised by, its particle size range of the silica dioxide granule is between 100 microns and 200 microns, its inside diameter ranges of the pipeline Between 500 microns and 1000 microns.
9. the cheap controller used in syphilis diagnosis micro fluidic device according to claim 1 based on new liquid stream driving principle, its It is characterised by, the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission Its other end of cable is connected with the higher-order of oscillation electric signal generator.
10. the cheap controller used in syphilis diagnosis micro fluidic device according to claim 1 based on new liquid stream driving principle, its It is characterised by, for its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units between 2 milliwatts and 2000 milliwatts, this is miniature The frequency of its ultrasonic wave operationally launched of ultrasonic transducer is between 100KHz and 12MHz.
CN201610728073.1A 2016-08-15 2016-08-15 Cheap controller used in syphilis diagnosis micro fluidic device based on new liquid stream driving principle Pending CN107754914A (en)

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