CN107754912A - The multichannel micro-fluidic chip device that a variety of hypotype swine flus detect simultaneously - Google Patents

The multichannel micro-fluidic chip device that a variety of hypotype swine flus detect simultaneously Download PDF

Info

Publication number
CN107754912A
CN107754912A CN201610728071.2A CN201610728071A CN107754912A CN 107754912 A CN107754912 A CN 107754912A CN 201610728071 A CN201610728071 A CN 201610728071A CN 107754912 A CN107754912 A CN 107754912A
Authority
CN
China
Prior art keywords
micro
fluidic chip
pipeline
substrate
hypotype swine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201610728071.2A
Other languages
Chinese (zh)
Inventor
李榕生
葛宇杰
蒋剑萍
葛光奇
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to CN201610728071.2A priority Critical patent/CN107754912A/en
Publication of CN107754912A publication Critical patent/CN107754912A/en
Pending legal-status Critical Current

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502707Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/50273Containers 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 means or forces applied to move the fluids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502746Containers 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 means for controlling flow resistance, e.g. flow controllers, baffles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502761Containers 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
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531Production of immunochemical test materials
    • G01N33/532Production of labelled immunochemicals
    • G01N33/535Production of labelled immunochemicals with enzyme label or co-enzymes, co-factors, enzyme inhibitors or enzyme substrates
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56983Viruses
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/026Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0631Purification arrangements, e.g. solid phase extraction [SPE]
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0645Electrodes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0832Geometry, shape and general structure cylindrical, tube shaped
    • B01L2300/0838Capillaries
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0887Laminated structure
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/12Specific details about materials
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/16Surface properties and coatings
    • B01L2300/161Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/16Surface properties and coatings
    • B01L2300/161Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B01L2300/165Specific details about hydrophobic, oleophobic surfaces
    • B01L2300/166Suprahydrophobic; Ultraphobic; Lotus-effect
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0433Moving fluids with specific forces or mechanical means specific forces vibrational forces
    • B01L2400/0439Moving fluids with specific forces or mechanical means specific forces vibrational forces ultrasonic vibrations, vibrating piezo elements
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2458/00Labels used in chemical analysis of biological material
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2469/00Immunoassays for the detection of microorganisms
    • G01N2469/10Detection of antigens from microorganism in sample from host
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Virology (AREA)
  • Food Science & Technology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Fluid Mechanics (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

The present invention relates to the multichannel micro-fluidic chip device that one kind of multiple hypotype swine flus detect simultaneously, belong to analysis testing field.The substrate physical presence series problem of hypotype swine flu diagnosis micro-fluidic chip is made using dimethyl silicone polymer i.e. PDMS that is cheap and easily processing.This case main points are, the selected PDMS with ecosystem surface of substrate, 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

The multichannel micro-fluidic chip device that a variety of hypotype swine flus detect simultaneously
Technical field
The present invention relates to the multichannel micro-fluidic chip device that one kind of multiple hypotype swine flus detect simultaneously, the micro-fluidic dress It is to diagnose the special purpose device of hypotype swine flu antigen based on antigen/antibody specific reaction to put, and belongs to analysis testing field.
Background technology
Multichannel micro-fluidic hypotype swine flu diagnostic techniques background, it is special to may refer to the grade inventions of CN 201110311127.1 Sharp 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 hypotype swine flu diagnosis multichannel micro-fluidic chip field, Form a kind of new hypotype swine flu diagnosis multichannel micro-fluidic device.
The present invention solves the technical problem by following scheme, and the device that the program provides is one kind of multiple hypotype pig streams The multichannel micro-fluidic chip device of sense detection simultaneously, the structure of the micro fluidic device include multichannel micro-fluidic chip, and this is micro- The structure of 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 piece The channel structure via mould pressing process or etching technics formation, the base are contained in shape thing, that face towards the cover plate of the substrate Piece also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or simple drilling technology shape Into window structure, be bonded to each other the substrate that is installed together and the cover plate be built into jointly containing pipeline configuration and with Connected liquid pool structure micro-fluidic chip, the locations of structures of the pipeline be located at the interface that the substrate and the cover plate are bonded to each other Region, 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 structure of the liquid pool Position, 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, remaining Under the liquid flowing in its chip when being located at the actual sample introduction test of the micro-fluidic chip of liquid pool its locations of structures terminal, should Terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is branched off via the manifold shape for being similarly positioned in the interface zone being bonded to each other Road 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 the terminal A remaining liquid pool UNICOM, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and right Electrode and reference electrode, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded hypotype The gold size sensitive membrane of swine flu specific antibody is formed, and the construction of the pipeline is in parallel construction, the pipeline in parallel construction It is made up of three lateral parallel connections, the quantity of the working electrode is three, the installation position difference of three working electrodes In three laterals, and, the specific antibody in its top layer gold size sensitivity membrane structure of three working electrodes It is the three kinds of hypotype swine flu antibody materials that can be specifically bound to hypotype swine flu antigen respectively, three kinds of antibody materials difference It is hypotype swine flu specific antibody H1N1、H3N2And H1N2, its material of the working electrode is that gold material or thermal decomposition are conductive Sheet or thread is presented in macromolecule material, its pattern of the working electrode, and emphasis is that its material of the substrate is polydimethylsiloxanes Alkane material, its surface of the substrate are the surfaces of primary form, the surface of the primary form its be intended to refer to not by any The surface of the primary form of surface chemical modification or the material of any surface chemical modification, the structure of the micro fluidic device are also wrapped Miniature ultrasonic transducer units are included, and, higher-order of oscillation electric signal transmission cable, one end of the higher-order of oscillation electric signal transmission cable Linked together with the miniature ultrasonic transducer units, the miniature ultrasonic transducer units are installed in the lid of the micro-fluidic chip with attaching The position of the neighbouring terminal of piece or substrate;Its major function of the miniature ultrasonic transducer units be micro-fluidic chip it is actual enter When sample is tested, the sample introduction end and the distance between the terminal and the miniature ultrasonic transducer units installation position difference are utilized And the difference on its ultrasonic intensity for being experienced, its interfacial tension of sample introduction end described in induced synthesis and its boundary of the terminal Difference between the tension force of face, the interfacial tension difference between the micro-fluidic chip both ends can be at the both ends of the micro-fluidic chip Between form pressure gap, the pressure gap can drive sample solution to the end flow;It is soft and have elasticity this poly- two Its function of the substrate of methylsiloxane material is included with its property to the strong absorption of ultrasonic wave, and ultrasonic wave is inhaled strongly Receive, and thereby realize ultrasonic intensity within micro-fluidic chip terminal to the limited short distance between the sample introduction end Rapid decrement;And many silica dioxide granules, many silica dioxide granules are filled in the pipeline, the pipe Its tube chamber of road is filled up by many silica dioxide granules, and its particle size range of the silica dioxide granule is between 10 microns and 200 Between micron, the silica dioxide granule is its institute of silica crystalline particles, silica glass granule or silica composition Inorganic glass particles of the percentage by weight more than 80% are accounted for, a remaining liquid pool is also referred to as terminal liquid pool, the terminal liquid Some high hydroscopic resin particles are filled with pond, 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 hypotype swine flu specific antibody solution It is even, with point sample instrument point sample or specified structure position is coated on, and form its drying and forming-film.Hypotype in the gold size sensitive membrane Swine flu specific antibody be horseradish peroxidase or glucose oxidase mark hypotype swine flu antibody, the gold Glue sensitive membrane has been included as fixing above-mentioned each hypotype swine flu specific antibody and introducing complementary medium therein, the auxiliary Property medium such as chitosan, cellulose acetate, gelatin be 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 triple channel micro-fluidic chip, right respectively using multi-channel electrochemical analyzer device Three kinds of hypotype swine flu diagnostic 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 hypotype swine flu antigen molecules The hypotype swine flu of the corresponding horseradish peroxidase-labeled embedded by gold size sensitive membrane on electrode surface in each passage is special Property antibody capture.
2nd, the hypotype swine flu specific antibody of horseradish peroxidase-labeled resists with the hypotype swine flu in blood serum sample Original shape is into immune complex.
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 hypotype swine flu 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, 1,2,8 be the different liquid pool of three installation positions respectively, and 3 be manifold shape turnout, and 4,9,12 be installing respectively Position is different but three laterals parallel with one another for forming UNICOM's structure in parallel, and 5 be its top layer being installed in lateral 4 Specific antibody material in gold size sensitivity membrane structure is hypotype swine flu specific antibody H1N1Working electrode, 10 be installing The specific antibody material in its top layer gold size sensitivity membrane structure in lateral 9 is hypotype swine flu specific antibody H3N2Working electrode, 11 be the specific antibody material in its top layer gold size sensitivity membrane structure being installed in lateral 12 For hypotype swine flu specific antibody H1N2Working electrode, 6 be to electrode, and 7 be reference electrode, and 13 be dimethyl silicone polymer The substrate of material, 14 be cover plate, and 15 be higher-order of oscillation electric signal transmission cable, and 16 be miniature ultrasonic transducer units, and 17 be that this is micro- The sample introduction end of fluidic chip, 18 be the terminal of the micro-fluidic chip;It is micro-fluidic that arrow in legend indicates this 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 13 and cover plate 14 of installing together, the substrate 13 and cover plate 14 be plate object or tablet, and that face towards the cover plate 14 of the substrate 13 is contained via mould pressing process or etching technics The channel structure of formation, the substrate 13 also containing be connected with the channel structure and pierce the substrate 13 via mould pressing process, The window structure that etching technics or simple drilling technology are formed, is bonded to each other the substrate 13 being installed together and the cover plate 14 is common With the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto has been built into, the locations of structures of the pipeline is located at The interface zone that the substrate 13 is bonded to each other with the cover plate 14, its side of the window is blocked by the cover plate 14 and opposite side opens, The locations of structures of the window is exactly the locations of structures of the liquid pool, and the quantity of the liquid pool is three, and three liquid pools are respectively Liquid pool 1, liquid pool 2, liquid pool 8, two liquid pools therein are that liquid pool 1 and liquid pool 2 its locations of structures are located at entering for the micro-fluidic chip Sample end, a remaining liquid pool are liquid in its chip when liquid pool 8 its locations of structures is located at the micro-fluidic chip actual sample introduction test The terminal 18 of body flowing, the terminal 18 is located remotely from each other with the sample introduction end 17, and one end of the pipeline is mutually pasted via being similarly positioned in this The manifold shape turnout 3 of the interface zone of conjunction is liquid pool 1 and the UNICOM of liquid pool 2 with two liquid pools positioned at sample introduction end 17 respectively, is somebody's turn to do The other end of pipeline and a remaining liquid pool for the terminal 18 positioned at the micro-fluidic chip are the UNICOM of liquid pool 8, and, The working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode and reference electrode, the working electrode By conductive electrode and the gold size sensitive membrane for having embedded hypotype swine flu 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 three lateral parallel connections, the work The quantity for making electrode is three, and the installation position of three working electrodes is located in three laterals respectively, and, should Specific antibody in three working electrode its top layer gold size sensitivity membrane structures is respectively can specificity to hypotype swine flu antigen With reference to three kinds of hypotype swine flu antibody materials, three kinds of antibody materials are hypotype swine flu specific antibody H respectively1N1、H3N2 And H1N2, for specific expansion, 5 be the specific antibody thing in its top layer gold size sensitivity membrane structure being installed in lateral 4 Matter is hypotype swine flu specific antibody H1N1Working electrode, 10 be its top layer gold size sensitive membrane being installed in lateral 9 Specific antibody material in structure is hypotype swine flu specific antibody H3N2Working electrode, 11 be to be installed in lateral The specific antibody material in its top layer gold size sensitivity membrane structure in 12 is hypotype swine flu specific antibody H1N2Work electricity Pole, its material of the working electrode are gold material or thermal decomposition conducting polymer material, and its pattern of the working electrode is presented Sheet is thread, and emphasis is, its material of the substrate 13 is dimethyl silicone polymer material, and its surface of substrate 13 is primary form Surface, the surface of the primary form its be intended to refer to and do not pass through any surface chemical modification or any surface chemical modification The material primary form surface, the structure of the micro fluidic device also includes miniature ultrasonic transducer units 16, and, high frequency Electric signal transmission cable 15 is vibrated, one end of the higher-order of oscillation electric signal transmission cable 15 connects with the miniature ultrasonic transducer units 16 It is connected together, the miniature ultrasonic transducer units 16 are installed in cover plate 14 or the neighbouring institute of substrate 13 of the micro-fluidic chip with attaching State the position of terminal 18;Its major function of the miniature ultrasonic transducer units 16 is the profit in micro-fluidic chip actual sample introduction test With the sample introduction end 17 and the distance between the terminal 18 and the installation position of miniature ultrasonic transducer units 16 difference and Difference on its ultrasonic intensity experienced, its interfacial tension of sample introduction end 17 described in induced synthesis and described its boundary of terminal 18 Difference between the tension force of face, the interfacial tension difference between the micro-fluidic chip both ends can be at the both ends of the micro-fluidic chip Between form pressure gap, the pressure gap can drive sample solution to be flowed to the terminal 18;It is soft and have elasticity this is poly- Its function of the substrate 13 of dimethyl siloxane material is included with its property to the strong absorption of ultrasonic wave, ultrasonic wave is carried out strong Absorb, and thereby realize ultrasonic wave within micro-fluidic chip terminal 18 to the limited short distance between the sample introduction end 17 The rapid decrement of intensity;And many silica dioxide granules, many silica dioxide granules are filled in the pipeline, Its tube chamber of the pipeline is filled up by many silica dioxide granules, and its particle size range of the silica dioxide granule is between 10 microns Between 200 microns, the silica dioxide granule is silica crystalline particles, silica glass granule or silica composition Its inorganic glass particles of shared percentage by weight more than 80%, a remaining liquid pool are also referred to as terminal liquid pool, the end Some high hydroscopic resin particles are filled with the liquid pool of end, its opening end of the terminal liquid pool is covered by breathable microporous film.
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 16 and higher-order of oscillation electric signal transmission cable 15 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 16 are commercially available;It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal transmission cable 15 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 multichannel micro-fluidic chip device that more than kinds of hypotype swine flu detects simultaneously, the structure of the micro fluidic device include leading to more Road 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 substrate and Cover plate is plate object or tablet, and that face towards the cover plate of the substrate is contained via mould pressing process or etching technics shape Into channel structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etch work The window structure that skill or simple drilling technology are formed, it is bonded to each other the substrate being installed together and is built into jointly with the cover plate Micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the locations of structures of the pipeline are located at the substrate with being somebody's turn to do The interface zone that cover plate is bonded to each other, its side of the window is blocked by the cover plate and opposite side opens, the locations of structures of the window It is exactly the locations of structures of the liquid pool, the quantity of the liquid pool is three, and it is micro- that its locations of structures of two liquid pools therein is located at this The sample introduction end of fluidic chip, its locations of structures of a remaining liquid pool are located at its chip when the actual sample introduction of the micro-fluidic chip is tested The terminal of interior liquid flowing, the terminal are located remotely from each other with the sample introduction end, and one end of the pipeline is bonded to each other via this is similarly positioned in Interface zone manifold shape turnout respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline with positioned at should A remaining liquid pool UNICOM for the terminal of micro-fluidic chip, and, sequentially it is respectively installed in different positions in the pipeline The working electrode put and to electrode and reference electrode, the working electrode is by conductive electrode and is attached to the conduction Property electrode on embedded hypotype swine flu specific antibody gold size sensitive membrane form, the construction of the pipeline is in parallel construction, The pipeline in parallel construction is made up of three lateral parallel connections, and the quantity of the working electrode is three, three works The installation position for making electrode is located in three laterals respectively, and, its top layer gold size of three working electrodes is sensitive Specific antibody in membrane structure is the three kinds of hypotype swine flu antibody things that can be specifically bound to hypotype swine flu antigen respectively Matter, three kinds of antibody materials are hypotype swine flu specific antibody H respectively1N1、H3N2And H1N2, its material of the working electrode is Sheet or thread is presented in gold material or thermal decomposition conducting polymer material, its pattern of the working electrode, it is characterised in that should Its material of substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, the surface of the primary form It is intended to refer to not by any surface chemical modification or the table of the primary form of the material of any surface chemical modification Face, the structure of the micro fluidic device also include miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, the height Frequency vibration swings one end of electric signal transmission cable and the miniature ultrasonic transducer units link together, miniature ultrasonic transducer units patch The position of the cover plate of the micro-fluidic chip or the neighbouring terminal of substrate is installed in attachedly;Its master of the miniature ultrasonic transducer units It is in the actual sample introduction test of micro-fluidic chip to want function, is changed using the sample introduction end and the terminal with the miniature ultrasonic Difference in the distance between energy device installation position difference and its ultrasonic intensity experienced, sample introduction described in induced synthesis Hold the difference between its interfacial tension and the terminal its interfacial tension, the interfacial tension between the micro-fluidic chip both ends is poor Different to form pressure gap between the both ends of the micro-fluidic chip, the pressure gap can drive sample solution to the terminal 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 short between the sample introduction end The rapid decrement of ultrasonic intensity is realized within distance;And many silica dioxide granules, many silica dioxide granules Be filled in the pipeline, its tube chamber of the pipeline is filled up by many silica dioxide granules, the silica dioxide granule its For particle size range between 10 microns and 200 microns, the silica dioxide granule is silica crystalline particles, silica glass Particle or silica composition its inorganic glass particles of shared percentage by weight more than 80%, a remaining liquid pool Also referred to as terminal liquid pool, the terminal liquid pool is interior to be filled with some high hydroscopic resin particles, and its opening end of terminal liquid pool is by ventilative micro- Pore membrane is covered.
2. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 detect simultaneously, its feature It is, the pipeline and the lateral and the manifold shape turnout are capillary channel.
3. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 detect simultaneously, its feature It is, the thermal decomposition conducting polymer is the electric conductivity material formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated Material.
4. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 detect simultaneously, its feature Be, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the length of the working electrode Degree is between 1 micron to 15000 microns.
5. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 detect simultaneously, its feature It is, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 detect simultaneously, its feature It is, the cover plate its material in structure is dimethyl silicone polymer material.
7. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 detect simultaneously, its feature Be, positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with the remainder positioned at the micro-fluidic chip terminal A liquid pool between air line distance between 3 centimetres and 7 centimetres;Described its thickness of cover plate and substrate in structure is situated between Between 1.0 millimeters and 5.0 millimeters.
8. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 detect simultaneously, its feature Be, its particle size range of the silica dioxide granule between 100 microns and 200 microns, its inside diameter ranges of the pipeline between Between 500 microns and 1000 microns.
9. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 detect simultaneously, its feature It is, the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission cable Its other end is connected with the higher-order of oscillation electric signal generator.
10. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 detect simultaneously, its feature It is, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 2 milliwatts and 2000 milliwatts, the miniature ultrasonic The frequency of its ultrasonic wave operationally launched of wave transducer is between 100KHz and 12MHz.
CN201610728071.2A 2016-08-15 2016-08-15 The multichannel micro-fluidic chip device that a variety of hypotype swine flus detect simultaneously Pending CN107754912A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610728071.2A CN107754912A (en) 2016-08-15 2016-08-15 The multichannel micro-fluidic chip device that a variety of hypotype swine flus detect simultaneously

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610728071.2A CN107754912A (en) 2016-08-15 2016-08-15 The multichannel micro-fluidic chip device that a variety of hypotype swine flus detect simultaneously

Publications (1)

Publication Number Publication Date
CN107754912A true CN107754912A (en) 2018-03-06

Family

ID=61264887

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610728071.2A Pending CN107754912A (en) 2016-08-15 2016-08-15 The multichannel micro-fluidic chip device that a variety of hypotype swine flus detect simultaneously

Country Status (1)

Country Link
CN (1) CN107754912A (en)

Similar Documents

Publication Publication Date Title
CN107754915A (en) Interfacial characteristics is relied on to carry out the cheap micro fluidic device of cholera diagnosis of liquid stream driving
CN107754909A (en) The special cheap AIDS diagnosis micro fluidic device of fluid type of drive
CN107754878A (en) Using the controller used in syphilis diagnosis of interfacial characteristics transmission liquid stream with cheap micro fluidic device
CN107349978A (en) Additional driving liquid stream is easy to the hypotype swine flu detection means of removal with component
CN107344125A (en) The special cheap AIDS diagnosis micro fluidic device of fluid type of drive
CN107754906A (en) Strong hypotype swine flu detection chip apparatus of the hydrophobic PDMS as substrate material
CN107754874A (en) The strong hydrophobic controller used in syphilis diagnosis Multichannel device of its substrate of micro-fluidic chip
CN107754912A (en) The multichannel micro-fluidic chip device that a variety of hypotype swine flus detect simultaneously
CN107754916A (en) The multichannel micro-fluidic chip device of a variety of hypotype swine flus is detected simultaneously
CN107345959A (en) The multichannel micro-fluidic chip device of a variety of hypotype swine flus is detected simultaneously
CN107345960A (en) Interfacial characteristics is relied on to carry out the cheap micro fluidic device of cholera diagnosis of liquid stream driving
CN107754880A (en) Additional driving liquid stream is easy to the hypotype swine flu detection means of removal with component
CN107754879A (en) The special cheap cholera diagnosis micro fluidic device of sap flow process mode
CN107754873A (en) The hypotype swine flu detection device that fluid driving can be removed rapidly with component
CN107754877A (en) Substrate material is PDMS cholera diagnosis multi-channel chip device
CN107754911A (en) The easily-disassembled cholera diagnosis device of liquid stream driving is carried out by means of interfacial characteristics
CN107349980A (en) The hypotype swine flu detection device that fluid driving can be removed rapidly with component
CN107345963A (en) Using the controller used in syphilis diagnosis of interfacial characteristics transmission liquid stream with cheap micro fluidic device
CN107349975A (en) The easily-disassembled cholera diagnosis device of liquid stream driving is carried out by means of interfacial characteristics
CN107754913A (en) Liquid stream driving is with the easily-disassembled controller used in syphilis diagnosis micro fluidic device of adapter
CN107754902A (en) Its substrate of chip uses the cholera diagnosis micro fluidic device of strong hydrophobic material
CN107754914A (en) Cheap controller used in syphilis diagnosis micro fluidic device based on new liquid stream driving principle
CN107377012A (en) Substrate material is PDMS cholera diagnosis multi-channel chip device
CN107754881A (en) Easily-disassembled hypotype swine flu multi-channel testing device comprising electromagnetism auxiliary part
CN107754876A (en) The cholera diagnosis micro fluidic device that can be fast removed for the annex for driving liquid stream

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20180306

WD01 Invention patent application deemed withdrawn after publication