CN107362838A - The readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function - Google Patents

The readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function Download PDF

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CN107362838A
CN107362838A CN201610356760.5A CN201610356760A CN107362838A CN 107362838 A CN107362838 A CN 107362838A CN 201610356760 A CN201610356760 A CN 201610356760A CN 107362838 A CN107362838 A CN 107362838A
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micro
pipeline
substrate
liquid stream
fluidic chip
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李榕生
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    • 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
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416Systems
    • 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
    • B01L2200/10Integrating 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
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Electrochemistry (AREA)
  • Molecular Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Dispersion Chemistry (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

The present invention relates to a kind of readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function, 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.This case main points are, the selected PDMS with ecosystem surface of substrate, and the chain ring type magnetic holding device for being equiped with miniature ultrasonic transducer units socket is positioned at the sample liquid stream terminal of the micro-fluidic chip its neighbor positions, sample liquid stream is induced to be flowed from its sample introduction end of the chip along its pipeline of the chip to the terminal direction with ultrasonic wave, 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.

Description

The readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function
Technical field
The present invention relates to a kind of readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function, the micro fluidic device is Based on antigen/antibody specific reaction come the special purpose device of Diagnosis of Syphilis antigen, belong to analysis testing field.
Background technology
The micro-fluidic controller used in syphilis diagnosis technical background of associated multi-channel, may refer to the applications for a patent for invention such as CN200910152141.4 Case.
Only for the microflow control technique overall general picture of itself, it may refer to famous micro-fluidic expert Mr. Lin Ping Cheng and go out not long ago Monograph " diagram Microfluid based Lab on a chip ", the monograph is published via Science Press, and the monograph is for microflow control technique Past, 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, the substrate On fluid course, before upper cover plate is assembled, it is apparent on see to be exactly some conduits, wait until cover cover plate thereon after, Just really closure forms the fluid course, and the conduit inner surface of the conduit is together with the part cover plate structure that surround the conduit Into described fluid course;So, it is clear that assemble the fluid course after completing, the main portion of its inner surface area Point it is the inner surface area of that conduit, in other words, the state or property of the conduit inner surface substantially determine that the liquid stream is led to The integrality or property in road;Therefore say, the inner surface state or inner surface property of this conduit of the structure on substrate are crucial Factor;In principle, any material that can be kept or keep its solid forms substantially, can be used to make substrate and lid Piece, such as, the material that can act as substrate and cover plate can be for example poly- diformazan of monocrystalline silicon piece, quartz plate, sheet glass, high polymer Radical siloxane, polymethyl methacrylate, makrolon etc.;Certainly, the selection of substrate and the selection of cover plate can with identical, It can also differ;From the point of view of material consumption, manufacture difficulty and application popularization prospect etc. etc., exist between these materials Not small difference, the especially selection of that substrate, have a great influence.
In various substrate making materials, dimethyl silicone polymer, i.e. PDMS, comparatively very easily shaping, so Substrate on to make conduit extremely simple, and the lower cost for material, substrate is made with the polydimethyl siloxane material, Conduit is suppressed or etched thereon, and is engaged with the cover plate that the cheap material such as glass or polypropylene or other plastic sheets makes, seemingly It is a kind of more satisfactory selection;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 being extremely easy to Popularization, promote.
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 Hydrophobic material, conduit is built on this material, if without being operated for the modified of the conduit surface, then, it is overall After assembling is completed, that is, after covering cover plate, because the conduit its inner surface in structure is occupied in most fluid course Surface, then, its strong hydrophobic property of the PDMS conduits inner surface, is deciding factor, and it can be similar to water-soluble The fine liquid stream of polar liquid of liquid 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 is pretty troublesome for the modified operation of PDMS conduit inner surfacesThat falls nor this problem, forms serious technical puzzlement , it is another problem:PDMS polymer molecules inside its body phase of this PDMS material substrate, which have from trend surface, to be expanded Dissipate, the characteristic of migration, the characteristic that PDMS polymer molecules are diffused to the surface, migrated automatically inside this substrate body phase, will make The sufficiently long time must can not be maintained by the state after the modification of its inner surface of that conduit of surface modifying and decorating, that Holding time for conduit its inner surface state after surface-modified is substantially only sufficient to the time for completing laboratory internal test experiments Need;In other words, by surface is modified or the PDMS conduit inner surfaces of surface modification, after it is modified or modification is said The surface state formed afterwards can not be lasting, but soon automatically tends to or say the surface state before becoming surface modification again, The strong hydrophobic surface state of that script is returned in the shorter time, then, just think, such micro-fluidic chip energy Enough a large amount of making, mass storages, it is widely popularized, answer is it is obvious that is, impossible.On this PDMS material Conduit, if not doing surface modification, it can not pump and pass through similar to the fine liquid stream of polar solvent of the aqueous solution, chip also just cannot Use;And if having done surface modification, its state after modifying can not be persistently kept 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 surfactant is added in sample to be tested solution, with Just 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 being tested in sample solution Combination occurs for composition so that tested composition can not be detected normally or it is detected ratio and dubiously reduced;Live on the surface Property agent is possibly even fully wrapped around by tested composition with micelle form so that tested composition can not be detected or identify;Therefore, should 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 inner surface can be released Decorating state can not persistently, chip can not largely make, largely lay in and then be widely popularized and such a make the numerous specialties in this area The puzzlement that personnel 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 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, directly It is trapped within the body phase of PDMS substrates to heavy, in fact, this process, is partly also due to inside PDMS material body phase 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. Continuously from inside PDMS body phases to those polymer molecules of its diffusion into the surface, migration, its result moved, be by Gradually those are involved within the body phase of PDMS substrates by the large biological molecule of adsorption, briefly, these are inhaled Attached large biological molecule is exactly to be swallowed up by PDMS substrate body phases;So, this PDMS substrates body phase swallows up large biological molecule Phenomenon, the influence caused by it, 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 large biological molecule, So, as the large biological molecule of experiment test object, its disappearance will not stop because surface saturation is adsorbed, but, no It is disconnected adsorbed, also constantly swallowed up.
On PDMS substrates in related experiment test process its body phase constantly swallow up test associated biomolecule macromolecular phenomenon, separately It is to say that one kind, which is explained, substantial amounts of Minute pores in PDMS body phases be present, and associated biomolecule macromolecular is by after adsorption, depression Into these Minute pores, and then swallowed up;However, inventor thinks, those can allow the air point of miniature scale Son 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, two Person's difference on yardstick is huge, must not make sweeping generalizations.Explanation is bypassed, in any case, the biology as dependence test analysis object Macromolecular is adsorbed by PDMS substrate conduits inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is known objective deposits Phenomenon.
, can be from containment PDMS surfaces to life in order to prevent swallow up effect of this PDMS substrate bodies relative to large biological molecule The absorption of thing macromolecular 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 changes Surface state after property can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface automatically, The process of migration, soon it can become that conduit inner surface state being modified by surface chemical modification again script strong hydrophobic 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 bases Its conduit inner surface of piece 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 enough reaches Growth stage contains the absorption process of the PDMS substrate conduit inner surfaces to large biological molecule, and then prevents 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 the numerous specialties in this area as another problem addressed above 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.The hardly possible Also be present many year in topic, so far, also not yet properly settled.
Third, the polydimethyl siloxane material, namely PDMS material, the active force very little wherein between polymer molecule, its The polymer molecule of low polymerization degree inside body phase is in constantly into the dynamic process of surface migration, therefore, includes PDMS bases 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 molecule not for the chip of sheet material Migrate disconnectedly, pour into the surface and change, the change of its pattern is somewhat similarly to Rheological Deformation, trickling deformation or deformation of creep institute Pattern changes caused by possible;In the higher PDMS material of some low polymerization degree component ratios, this kind is somewhat similarly to flow The phenomenon of deformation, trickling deformation or the deformation of creep can show must be than more significant;Its shaping of chip of this kind comprising PDMS substrates The dynamic of inner-walls of duct surface topography afterwards changes property, namely the described property for being somewhat similarly to Rheological Deformation or trickling deformation Property or the deformation of creep property, this case applies mechanically the word of rheology one, integration, also referred to as the rheological equationm of state or Rheological Deformation property, The dynamic of corresponding inner-walls of duct face pattern changes, and this case is also referred to as rheology;As described above, because this kind of material its own The certain Rheological Deformation property as described above having, its manufactured goods actually can at leisure Rheological Deformation and cause the manufactured goods whole Individual structural form changes;Influence caused by its Rheological Deformation property, in terms of macroscopic perspective be it is subtle, still, For the very fine micro-fluidic chip of its internal structure, the rheological equationm of state can but cause bigger influence, therefore, in advance The fluid course namely the pipeline formed when first making, because the wall of its tube chamber of pipeline is mainly PDMS materials Wall, so, the cross-sectional area of the pipeline can actually taper into because of rheology over time, in other words, Due to the rheology, can more it become more for natively finer its tube chamber of the pipeline that liquid sample flows through Narrow, in the case of flow time is sufficiently long, or even the tube chamber of the pipeline can partly be closed or fully closed, and then be caused Sample fluid course is thoroughly blocked, the journey for closing or fully closing with being even also not reaching to its luminal part of pipeline Degree, its fluid passage that can be provided of that pipeline narrow because of rheology, then, in pipeline, its inner surface is exactly originally strong It is strong it is hydrophobic in the case of, aqueous sample liquid is just more difficult to by becoming narrower micro-channel so because of rheology, then, The influence of substrate rheology how is resisted, maintains the basic framework of the pipeline that gross distortion does not occur for a long time, also, keep the pipeline Long-term unobstructed, the problem of being 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, solve what is addressed above totally A series of problems, also, the solution is applied to controller used in syphilis diagnosis multichannel micro-fluidic chip field, formed a kind of new Controller used in syphilis diagnosis multichannel micro-fluidic device.
The present invention solves the technical problem by following scheme, and the device that the program provides is a kind of liquid stream driving function structure The readily removable controller used in syphilis diagnosis micro fluidic device removed of part, the structure of the micro fluidic device include multichannel micro-fluidic chip, and this is micro-fluidic The structure of chip includes being bonded to each other installing substrate and cover plate together, and the substrate and cover plate are plate object or tablet, The channel structure via mould pressing process or etching technics formation is contained in that face towards the cover plate of the substrate, and the substrate also contains Be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or simple drilling technology formed window knot Structure, it is bonded to each other the substrate being installed together and has been built into jointly containing pipeline configuration and the liquid pool being attached thereto with the cover plate The micro-fluidic chip of structure, the locations of structures of the pipeline are located at the interface zone that the substrate is bonded to each other with the cover plate, the window its Side is blocked by the cover plate and opposite side opens, and the locations of structures of the window is exactly the locations of structures of the liquid pool, the liquid pool Quantity is three, and its locations of structures of two liquid pools therein is located at the sample introduction end of the micro-fluidic chip, its knot of a remaining liquid pool Structure position is located at the terminal of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, and the terminal and the sample introduction end are mutual It is remote, one end of the pipeline via be similarly positioned in the manifold shape turnout of the interface zone being bonded to each other respectively with positioned at sample introduction end The Liang Ge liquid pools UNICOM, the other end of the pipeline and a remaining liquid pool for the terminal positioned at the micro-fluidic chip join It is logical, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode and reference electrode is described Working electrode is 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, and, should Specific antibody in four working electrode its top layer gold size sensitivity membrane structures is can be specifically bound to Treponema pallidum antigen four respectively Kind syphilis antibody material, four kinds of antibody materials are syphilis specific antibody TP0684, TP0453, TP0821 and TP0319 respectively, Its material of the working electrode is gold material or thermal decomposition conducting polymer material, the working electrode its pattern present sheet or Thread, emphasis is that its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, should The surface of primary form its be intended to refer to the not no material by any surface chemical modification or any surface chemical modification The surface of primary form, the structure of the device also include chain ring type magnetic holding device, and six are shared in its structure of the chain ring type magnetic holding device Individual link, the link is in strip, shaft-like or bar-shaped, and each adjacent link is hinged to form chain link, its profile wheel of the chain link Wide hexagonal cyclic structure, its locations of structures of each drift angle of the hexagonal annular structure is articulated structure position, six side Two therein of shape cyclic structure is magnetic conductivity material in the link of opposite side position its material, the remainder of the hexagonal annular structure Its material of four processes is non-magnetic material, and the non magnetic material refers to the material not responded strongly to externally-applied magnetic field, Magnet exciting coil is wound with a link among two links of the magnetic conductivity material, this is wound with the link of magnet exciting coil at it The pole shoe of a magnetic conductivity material is respectively equiped with the both sides neighbor positions of magnet exciting coil, shares two pole shoes, two poles Boots are directed to the link of another magnetic conductivity material, attached on its surface of the link of another magnetic conductivity material it is fixed be equiped with it is micro- Type ultrasonic transducer, the chain ring type magnetic holding device socket of electromagnetism adhesive strength is relied on to be positioned at its described end of the micro-fluidic chip The close position at end, and, higher-order of oscillation electric signal transmission cable, one end of the higher-order of oscillation electric signal transmission cable is micro- with this Type ultrasonic transducer links together;The chain ring type magnetic holding device provides a function of facilitating the device to disassemble;This is miniature Its major function of ultrasonic transducer be in the test of micro-fluidic chip actual sample introduction, using the sample introduction end and the terminal with Difference in the distance between miniature ultrasonic transducer units installation position difference and its ultrasonic intensity experienced, induction The difference formed between described its interfacial tension of sample introduction end and the terminal its interfacial tension, between the micro-fluidic chip both ends Interfacial tension difference can form pressure gap between the both ends of the micro-fluidic chip, the pressure gap can drive sample solution to The end flow;Softness simultaneously has its function of the substrate of the dimethyl silicone polymer material of elasticity including strong to ultrasonic wave with it The property of absorption, ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic chip terminal to limited between the sample introduction end Short distance within realize the rapid decrement of ultrasonic intensity;And many silica dioxide granules, many silica It is particles filled in the pipeline, 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 particle or silica composition its inorganic glass particles of shared percentage by weight more than 80%.
Its particle diameter of the silica dioxide granule can be that the basis between 10 microns and 200 microns is actually needed and is arbitrarily designated Particle diameter, 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, cuboid 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 preferred compared to above-mentioned Internal diameter of the pipeline scope, more tiny internal diameter of the pipeline or thicker internal diameter of the pipeline are also what this case was allowed.
The word of magnet exciting coil one art-recognized meanings of itself are known.
The word of magnetic conductivity material one art-recognized meanings of itself are known;Belong to magnetic conductivity material material such as pure iron, Silicon steel, soft magnetic ferrite etc..
Non magnetic material described in this case refers to the material not responded strongly to externally-applied magnetic field, belongs to the non magnetic material Material such as metallic copper, metallic zinc, ormolu, metallic aluminium, almag etc..
The be hinged word art-recognized meanings of itself field in Machine Design is known.
The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and syphilis specific antibody-solutions uniformly, uses point sample instrument Point sample is coated on specified structure position, and forms its drying and forming-film.Syphilis specific antibody in the gold size sensitive membrane is equal The syphilis antibody marked for horseradish peroxidase or glucose oxidase, the gold size sensitive membrane have been included as fixing above-mentioned each Syphilis specific antibody and introduce complementary medium therein, the complementary medium such as chitosan, cellulose acetate, gelatin Therein a kind of or their mixture.
The pipeline and the lateral and the manifold shape turnout in the microfluidic chip structure, its internal diameter chi It is very little to may each be arbitrarily selected size, still, for prepare liquid sample and reducing the consideration of reagent loss etc. less as far as possible, The passage of capillary level, the capillary level are preferably selected in the pipeline and the lateral and the manifold shape turnout Passage imply that its internal diameter passage suitable with the internal diameter of the capillary on ordinary meaning.Its inner passage of capillary it is transversal Face shape can be arbitrary shape, the shape of cross section is for example circular, oval, square, rectangle, bar shaped, certainly Can the linear of bending arbitrarily be present, also, the interior shape of the capillary is with the extension of pipeline, different parts Shape of cross section can also allow to be different shapes.Only for the word of capillary one, its art-recognized meanings is known.
What is be related in structure is the electrode of microsize to electrode and reference electrode, and its electrode shape may each be any choosing Fixed shape, the arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..It is described to electricity The art-recognized meanings of pole 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 scrotiform structure for transitional liquid storage Make, its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, the cavity shape such as cylindrical empty Cavity-like, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..The size of the liquid pool can be arbitrarily selected Size, still, in order to which less with prepare liquid sample and reduction reagent loss, the liquid pool is preferably capable of and capillary as far as possible The liquid pool of the microminiature of matching.
It is public only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field Know.
Various sizes, variously-shaped ultrasonic transducer are commercially available;Commercially available miniature ultrasonic transducer units its sizes can be with It is small to arrive 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 itself and Speech, is known general technology for the professional in ultrasonic technology field.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;Equally Ground, 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 transmission electricity Its other end of 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, for the professional in ultrasonic technology field, it is It is 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 be between 5 milliwatts and 9000 milliwatts it 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, the annex such as multiple tracks electrochemical workstation etc., institute certainly The art-recognized meanings for stating multiple tracks electrochemical workstation are known.Each working electrode for being related in this case microfluidic chip structure and , can be respectively via corresponding special the corresponding interface got lines crossed with the multiple tracks electrochemical workstation to electrode and reference electrode etc. Coupled.It is described that special to get lines crossed be for each the corresponding interface of each electrode and the multiple tracks electrochemical workstation is carried out into phase The private cable being mutually coupled with.The micro-fluidic chip in this case device, its structure can also include micro-valve, the number of the micro-valve Measure unlimited, according to being actually needed, the micro-valve can be installed in the position of any required installation in the microfluidic chip structure; For the word of micro-valve one for the professional of micro fluidic chip technical field, the art-recognized meanings of itself are known;The micro-valve The manufacturing technology of itself 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, it is however recommended to Or say preferable its scope of the diameter between 0.1 micron to 2000 microns;The length of the working electrode can permit Permitted 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 at 1 micron To between 15000 microns.
The gold size that the working electrode surface layer is installed in by spraying or point sample instrument point sample or the coating of other appropriate process is quick Feel film, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness, still, push away Preferable thickness is between 10 nanometers and 200 nanometers to the thickness recommended in other words.
The cover plate in chip structure, its material can allow to be any electrical insulating property material, such as:Polypropylene, glass 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 this is remaining Air line distance between one liquid pool can be arbitrarily selected suitable distance as needed, and still, the preferred value of the distance is Between 3 centimetres and 7 centimetres.
Described its thickness of cover plate and substrate can allow be any setting be easy to assembling thickness, the thickness of recommendation or say preferably Thickness be 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 running of this case micro-fluidic chip In, 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, drive liquid Stream flows in the capillary channel of the four-way micro-fluidic chip, using four-way electrochemical analytical instrument respectively to four kinds of syphilis Diagnostic antigen is 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 passage The syphilis specific antibody capture for the corresponding horseradish peroxidase-labeled that gold size sensitive membrane embeds on electrode surface.
2nd, the syphilis specific antibody of horseradish peroxidase-labeled forms immune complex with the Treponema pallidum antigen in blood serum sample.
3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, using the above-mentioned reaction of amperometric detection Caused curent change, 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 relies on the socket of electromagnetism adhesive strength fixed in the terminal of the micro-fluidic chip Chain ring type magnetic holding device described in position, installation miniature ultrasonic is attached in the chain ring type magnetic holding device one magnetic conductivity link and is changed Energy device, with the ultrasonic wave of miniature ultrasonic transducer units transmitting low-power, high-frequency band, meanwhile, utilize dimethyl silicone polymer Its strong absorbability to ultrasonic wave of substrate, in shorter distance, it is, from the terminal to the sample introduction end it Between only several centimeters yardsticks very short distance in, reach the rapid decrement of ultrasonic intensity, thereby in the institute of the micro-fluidic chip State the difference that the interfacial tension is caused at both ends, and then, using the interfacial tension between the both ends difference its formed this two Pressure gap between end, driving sample liquid stream flow in the pipeline to the terminal direction.By this case liquid stream driving side Case, the equipment of traditional Micropump etc is altogether dispensed with;The micro-fluidic chip of Micropump is eliminated, its structure is more succinct, Its production process is less, and its cost of manufacture is lower, and this kind of succinct structure is more beneficial for the low cost application for reaching micro-fluidic chip.
Its scheme of this case and by the pipeline except electrode installation take up space in addition to all clearance spaces all use described in Silica dioxide granule fills up.Those are filled in the silica dioxide granule in pipeline, and this case is filled out to its overall abbreviation silica dioxide granule Fill thing, its function includes support, withstands the tube chamber of the pipeline its inwall so that the tube chamber of the pipeline from because of the rheology and Narrow, prevent its reduced cross-sectional area of the tube chamber of the pipeline or even close, so as to maintain the basic framework of the pipeline not send out for a long time Raw serious deformation.
Numerous silica dioxide granule entities are mutually banked up under this case framework together at random in the pipeline, the silica The function of grain filler, also includes with the hydrophilic surface of its silica dioxide granule, utilizes each adjacent silicon dioxide particle certainly Mutual formed complications are continuous and its inner surface that is mutually close together by water-wetted surface has the sky of hydrophilic nmature Gap, in the hydrophilic fluid channel of the pipeline Inner Constitution network morphology, the having all the time although this complications can be continuous The fluid channel of hydrophilic nmature, then, inside the tube chamber of the pipeline simultaneously and a plurality of fluid channel deposited its synthesis, The effect of integrated, cumulative superposition in other words, is the equal of the relatively fine hydrophilic capillary channel of caliber;The complications Its presence of continuous hydrophilic fluid channel, counteracts its surface of the PDMS substrates of the primary form to a large extent The flow resistance for liquid sample caused by strong hydrophobic property;In other words, because of liquid sample its account for maximum ratio into It is water to divide, and liquid sample is substantially exactly the aqueous solution, and therefore, the presence of the silica dioxide granule filler can be significantly Overcome with the unmodified PDMS substrates of hydrophobic property and surface its to the aqueous solution it is incompatible, repel and barrier effect, And then 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 the titanium dioxide The rigid of silicon grain filler ties up, on lumen wall wall still can also be exposed its face of the surface of part hydrophobic property Product is already dramatically reduced, and the area on its still exposed part surface for belonging to hydrophobic property does not have far smaller than The wall surface area of the hydrophobic property of the lumen wall wall in the presence of silica dioxide granule filler;So, at this Under the case framework, in its lumen of the pipeline, its remaining hydrophobic surface increases surface newly with hydrophilic part, that it is superimposed, comprehensive , summation, cumulative technique effect, be to form the surface for tending to be hydrophilic on the whole;In other words, in the pipeline Inside tube chamber, its interfacial tension between sample solution of the part surface of remaining hydrophobic property, plus that of hydrophilic nmature Newly-increased its interfacial tension between sample solution of surface in part, 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 its tube chamber inner surface of capillary glass tube with Interfacial tension between 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 the examination of this case mechanism drives Sample liquid flows 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 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 dioxies for pressing close to the lumen wall wall Silicon carbide particle is stuck in original place or is stuck in original place or embedding in-situ silica dioxide granule and remaining embedded in original place, the part The silica dioxide granule banked up with being mutually closely packed together each other incarceration together, due to this reason, the titanium dioxide Silicon grain filler just will not move in the pipeline easily, and silica dioxide granule therein, which is also substantially all, is locked in original Locate, 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 is between 10 microns and 200 microns, compared to general For organic molecule, general large biological molecule, the particle diameter of its particle of this case silica dioxide granule filler can be rated as it is huge, by In its huge particle diameter, and the inner surface of the surface of its polarity and the pipeline of strong hydrophobic PDMS materials can not be compatible Or say and mutually melt, then, the huge silica dioxide granule of this kind of particle diameter can not be by the interior table of the pipeline of PDMS materials Face 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 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, as described above, Under this case framework, rigid because of the silica dioxide granule filler ties up, still can also be exposed on lumen wall wall Its area of the surface of part hydrophobic property be already dramatically reduced, its still exposed part for belonging to hydrophobic property The area on surface be far smaller than no silica dioxide granule filler in the presence of the lumen wall wall dredge The wall surface area of aqueous nature;The reason for because of the rheology, it is close to those silica dioxide granules of lumen wall wall, gradually Ground is partially embedded into or is partly absorbed among the lumen wall wall, its direction pipe of the silica dioxide granule among the state The part surface of cavity wall wall is with having occurred and that the lumen wall wall of matching deformation is brought into close contact, then, in tube chamber The part wall that the matching is deformed and is brought into close contact with silica particles of having occurred and that in wall wall is actually It can not be contacted with flowing through the sample solution of pipeline, that is to say, that the wall of this part can not be to flowing through the examination of pipeline Sample solution large biological molecule therein and organic molecule produce suction-operated.Based on above-mentioned mechanism, then because filling up described Its presence of the silica dioxide granule filler of pipeline, the overwhelming majority of its lumen wall wall of the pipeline are tightly hidden Lid, these described walls tightly covered can not contact with flowing through the sample solution of the pipeline, be only remainder The hydrophobic surface for not being brought into close contact by its surface of silica dioxide granule, tightly covering of fraction may be connect with sample solution Touch, in other words, under this case framework, large biological molecule and organic molecule in sample solution its with hydrophobic PDMS walls Direct touch opportunity significantly reduce, thus, the lumen wall faces of PDMS materials its to large biological molecule and organic molecule Adsorptive hindrance and swallow up interference be greatly reduced;As described above, this case scheme is advantageous to exclude or weakens the absorption Interference is disturbed and swallowed up, is 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 the pipe for PDMS materials Road inner surface carries out the effect of chemical modification, and functioning as its this respect of this case is by the inner surface of pipeline of the PDMS materials By the surface modification of hydrophobic property into the surface of hydrophilic nmature, still, with general, usual PDMS surface chemical modifications its The hydrophilic chemical decorative layer retention time is short, hydrophilic effect can not keep that situation prolonged enough is different, and particle described in this case is huge Silica dioxide granule filler, its particle being stuck by rheology can not both be moved easily, and the particle of its huge particle diameter is more It can not be swallowed up easily by the inner-walls of duct of PDMS materials, therefore, its from this respect is similar to the technology of surface chemical modification Seen in effect, its technique effect of this case, be form it is permanent, can not erase, can not consume, not be corroded, not swallowed up , the hydrophilic surface reforming layer being not dissolved, it is just comparable to a kind of in PDMS base materials its relevant surfaces in effect The permanent hydrophilic modifying superficial layer of structure.
The technical scheme of this case dissolved totally address above to dimethyl silicone polymer substrate its apply related system Row technical barrier.Based on this case scheme, the very cheap polydimethyl siloxane material of this kind is just possible in the micro-fluidic chip Prepare, production, using etc. field play bigger effect.
Fixation is attached in the chain ring type magnetic holding device one magnetic conductivity link in this case structure and has installed the miniature ultrasonic Transducer, this architecture provides a function of facilitating the device to disassemble, in this way, the chain ring type magnetic holding device is led together with one The miniature ultrasonic transducer units attached in magnetic link just easily can be mutually disengaged with the micro-fluidic chip, then, the portion The component that dividing freely to depart from is reused many times in which just can circulate benignly;The architectural feature is advantageous to save making for the device Use cost.
Brief description of the drawings
Fig. 1 is the schematic diagram of this case device embodiment chip part construction, it is shown that the depression angle of this structure Under chip internal pipeline and the structural form of each electrode and each related liquid pool, do not depict the chain ring type electromagnetic clamp in the figure Tool and the miniature ultrasonic transducer units set up thereon and other annexes.
Fig. 2 be this case device chain ring type magnetic holding device its with outside side view rough under the micro-fluidic chip socket state, The legend and indicate the relative position relation under the socket state between each component.
Fig. 3 is the outside side view under another viewing angle of this case device;Fig. 3 viewing angle and Fig. 2 sight Angle is examined to be mutually perpendicular to.
In figure, 1,2,10 be the different liquid pool of three installation positions respectively, and 3 be manifold shape turnout, 4,7,11,14 It is that installation position is different but four laterals parallel with one another for forming UNICOM's structure in parallel respectively, 5 be to be installed in lateral 4 The working electrode that specific antibody material in its interior top layer gold size sensitivity membrane structure is syphilis specific antibody TP0684,6 It is that specific antibody material in its top layer gold size sensitivity membrane structure being installed in lateral 7 is syphilis specific antibody TP0453 working electrode, 12 be the specific antibody in its top layer gold size sensitivity membrane structure being installed in lateral 11 Material is syphilis specific antibody TP0821 working electrode, and 13 be that its top layer gold size being installed in lateral 14 is sensitive The working electrode that specific antibody material in membrane structure is syphilis specific antibody TP0319,8 be to electrode, and 9 be reference electricity Pole, 15 be chain ring type magnetic holding device, and 16 be the terminal of the micro-fluidic chip, and 17 be the sample introduction of the micro-fluidic chip End, 18 be the substrate of dimethyl silicone polymer material, and 19 be cover plate, and 20 be miniature ultrasonic transducer units, and 21 be high frequency vibrating Electric signal transmission cable is swung, 22,29 be the link of two magnetic conductivity materials positioned at different structure position respectively, and this two are led The link of magnetic material end-to-end relation each other in the structure shown here, 23,32 be two pole shoes positioned at different structure position respectively, 24th, 26,28,31,34,36 be six pin joints in six diverse locations respectively, and 25,27,33,35 distinguish It is the link of four non magnetic materials in four diverse locations, 30 be magnet exciting coil;The chain ring type electromagnetic clamp in legend Lamps structure is only the legend structure of signal, and the actual chain ring type magnetic holding device structure is not limited to the legend chain ring type electromagnetic clamp and signed an undertaking Structure;Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, its sample liquid stream Flow direction.
Embodiment
In this case that Fig. 1, Fig. 2 and Fig. 3 are shown embodiment, the structure of the micro fluidic device includes multichannel miniflow Chip is controlled, the structure of the micro-fluidic chip includes being bonded to each other the substrate 18 and cover plate 19 of installing together, the substrate 18 Be plate object or tablet with cover plate 19, that face towards the cover plate 19 of the substrate 18 contain via mould pressing process or Etching technics formed channel structure, the substrate 18 also containing be connected with the channel structure and pierce the substrate 18 via mould The window structure that pressure technique, etching technics or simple drilling technology are formed, the substrate 18 being installed together is bonded to each other with being somebody's turn to do Cover plate 19 has been built into the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto jointly, and the liquid pool is liquid Pond 1, liquid pool 2, liquid pool 10, the locations of structures of the pipeline are located at the interface zone that the substrate 18 is bonded to each other with the cover plate 19, Its side of the window is blocked by the cover plate 19 and opposite side opens, the locations of structures of the window be exactly the liquid pool 1, liquid pool 2, The locations of structures of liquid pool 10, the quantity of the liquid pool is three, and two liquid pools therein are liquid pool 1 and liquid pool 2 its structure bit Setting in the sample introduction end 17 of the micro-fluidic chip, a remaining liquid pool is that liquid pool 10 its locations of structures is located at the micro-fluidic chip The terminal 16 that liquid flows in its chip during actual sample introduction test, the terminal 16 are located remotely from each other with the sample introduction end 17, the pipeline One end via be similarly positioned in the manifold shape turnout 3 of the interface zone being bonded to each other respectively with the liquid pool positioned at sample introduction end 17 1 and the UNICOM of liquid pool 2, the other end of the pipeline and a remaining liquid for the terminal 16 positioned at the micro-fluidic chip Pond is the UNICOM of liquid pool 10, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode 8 with And reference electrode 9, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded syphilis specific The gold size sensitive membrane of antibody is formed, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by four laterals Parallel connection is formed, and the quantity of the working electrode is four, and the installation position of four working electrodes is located at four branches respectively In pipeline, four working electrodes are working electrode 5, working electrode 6, working electrode 12, working electrode 13 respectively, and, Specific antibody in its top layer gold size sensitivity membrane structure of four working electrodes can be specifically bound to Treponema pallidum antigen respectively Four kinds of syphilis antibody materials, four kinds of antibody materials be respectively syphilis specific antibody TP0684, TP0453, TP0821 and TP0319, for specifically deploying, 5 be that specificity in its top layer gold size sensitivity membrane structure being installed in lateral 4 resists Body material is syphilis specific antibody TP0684 working electrode, and 6 be that its top layer gold size being installed in lateral 7 is sensitive The working electrode that specific antibody material in membrane structure is syphilis specific antibody TP0453,12 be to be installed in lateral 11 The working electrode that specific antibody material in its interior top layer gold size sensitivity membrane structure is syphilis specific antibody TP0821,13 It is that specific antibody material in its top layer gold size sensitivity membrane structure being installed in lateral 14 is syphilis specific antibody TP0319 working electrode, the working electrode 5, working electrode 6, working electrode 12, working electrode 13 its material are yellow Golden material or thermal decomposition conducting polymer material, the working electrode 5, working electrode 6, working electrode 12, working electrode 13 Sheet or thread is presented in its pattern, and emphasis is, its material of the substrate 18 is dimethyl silicone polymer material, the substrate 18 its Surface is the surface of primary form, the surface of the primary form its be intended to refer to and do not pass through any surface chemical modification or any The surface of the primary form of the material of surface chemical modification, the structure of the device also include chain ring type magnetic holding device 15, the chain Share six links 22,25,27,29,33,35 in its structure of ring type magnetic holding device 15, the link 22,25,27, 29th, 33,35 in strip, shaft-like or bar-shaped, and each adjacent link is hinged to form chain link, and its appearance profile of the chain link is in Hexagonal annular structure, each drift angle of the hexagonal annular structure is its structure bit of drift angle 24,26,28,31,34,36 It is articulated structure position to put, links of two therein of the hexagonal annular structure in opposite side position be link 22,29 its Material is magnetic conductivity material, the remaining four processes of the hexagonal annular structure be link 25,27,33,35, its material it is equal It is non-magnetic material, the non magnetic material refers to the material not responded strongly to externally-applied magnetic field, the two of the magnetic conductivity material Individual link is that a link among link 22,29 is wound with magnet exciting coil 30 in link 29, and this is wound with magnet exciting coil 30 link 29 is respectively equiped with the pole shoe of a magnetic conductivity material in the both sides neighbor positions of its magnet exciting coil 30, shares two The individual pole shoe, the pole shoe are pole shoe 23 and pole shoe 32, two pole shoes are pole shoe 23 and pole shoe 32 be directed to it is another The link 22 of individual magnetic conductivity material, fixation is attached on its surface of the link 22 of another magnetic conductivity material and is equiped with miniature ultrasonic Wave transducer 20, the chain ring type magnetic holding device 15 socket of electromagnetism adhesive strength is relied on to be positioned at its described end of the micro-fluidic chip The close position at end 16, and, higher-order of oscillation electric signal transmission cable 21, the higher-order of oscillation electric signal transmission cable 21 One end links together with the miniature ultrasonic transducer units 20;The chain ring type magnetic holding device 15 provides one and facilitates the device The function of disassembling;Its major function of the miniature ultrasonic transducer units 20 is in the actual sample introduction test of micro-fluidic chip, utilizes institute State sample introduction end 17 and the distance between the terminal 16 and the installation position of miniature ultrasonic transducer units 20 difference and its institute The difference on ultrasonic intensity experienced, its interfacial tension of sample introduction end 17 described in induced synthesis and described its interface of terminal 16 Difference between tension force, the micro-fluidic chip both ends are that the interfacial tension difference between sample introduction end 17 and terminal 16 can be at this The both ends of micro-fluidic chip are to form pressure gap between sample introduction end 17 and terminal 16, and the pressure gap can drive sample molten Liquid flows to the direction of terminal 16;It is soft and have the substrate 18 of the dimethyl silicone polymer material of elasticity its function and include With its property to the strong absorption of ultrasonic wave, ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic chip terminal 16 The rapid decrement of ultrasonic intensity is realized within to the limited short distance between the sample introduction end 17;And many titanium dioxides Silicon grain, many silica dioxide granules are filled in the pipeline, and its tube chamber of the pipeline is by many silica Grain is filled up, and for its particle size range of the silica dioxide granule between 10 microns and 200 microns, the silica dioxide granule is two Inorganic glass of its shared percentage by weight of silica crystalline particles, silica glass granule or silica composition more than 80% Glass particle.
Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, its test liquid The flow direction of stream.
The chain ring type magnetic holding device 15 is depicted without in Fig. 1 and fixed installing is attached in one magnetic conductivity material link The miniature ultrasonic transducer units 20 and higher-order of oscillation electric signal transmission cable 21;Also, in Fig. 1, Fig. 2 and Fig. 3 It is depicted without the associate members such as the higher-order of oscillation electric signal generator and multiple tracks electrochemical workstation.
Involved magnetic conductive material and involved nonmagnetic substance market are on sale.
Involved miniature ultrasonic transducer units 20 are commercially available;It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal transmission cable 21 is commercially available;Can also be to ultrasonic transducer producer or cable special manufacturer Family's customization.
Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available;It can also be customized to relevant manufacturers.
Each working electrode in this example structure and electrode and reference electrode via each special cable or can be said respectively Get 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 readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function, the structure of the micro fluidic device includes 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 lid Piece is plate object or tablet, and what is formed via mould pressing process or etching technics contained in that face towards the cover plate of the substrate Channel structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or letter The window structure that single drilling technology is formed, it is bonded to each other the substrate being installed together and has been built into jointly with the cover plate and contain pipeline The micro-fluidic chip of structure and the liquid pool structure being attached thereto, the locations of structures of the pipeline are located at the substrate and mutually pasted with the cover plate The interface zone of conjunction, 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 manifold for being similarly positioned in the interface zone being bonded to each other Shape 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 the end A remaining liquid pool UNICOM at end, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and right Electrode and reference electrode, the working electrode by conductive electrode and be attached on the conductive electrode embedded syphilis spy The gold size sensitive membrane of heterogenetic antibody is formed, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by four branches Pipeline is in parallel to be formed, and the quantity of the working electrode is four, and the installation position of four working electrodes is located at described four respectively In lateral, and, the specific antibody in its top layer gold size sensitivity membrane structure of four working electrodes is that syphilis is resisted respectively Proper energy specific binding four kinds of syphilis antibody materials, four kinds of antibody materials be respectively syphilis specific antibody TP0684, TP0453, TP0821 and TP0319, its material of the working electrode are gold material or thermally decompose conducting polymer material, institute State working electrode its pattern presentation sheet or thread, it is characterised in that its material of the substrate is dimethyl silicone polymer material, should Its surface of substrate is the surface of primary form, the surface of the primary form its be intended to refer to and do not pass through any surface chemical modification , should or the surface of the primary form of the material of any surface chemical modification, the structure of the device also include chain ring type magnetic holding device Share six links in its structure of chain ring type magnetic holding device, for the link in strip, shaft-like or bar-shaped, each adjacent link is mutual It is be hinged to form chain link, the hexagonal cyclic structure of its appearance profile of the chain link, its structure of each drift angle of the hexagonal annular structure Position is articulated structure position, and in the link of opposite side position, its material is magnetic conductivity to two therein of the hexagonal annular structure Material, its material of the remaining four processes of the hexagonal annular structure is non-magnetic material, and the non magnetic material refers to pair The material that externally-applied magnetic field does not respond strongly, excitation wire is wound with a link among two links of the magnetic conductivity material Circle, the link for being wound with magnet exciting coil are respectively equiped with the pole of a magnetic conductivity material in the both sides neighbor positions of its magnet exciting coil Boots, two pole shoes are shared, two pole shoes are directed to the link of another magnetic conductivity material, another magnetic conductivity material Its surface of link on attach fixed chain ring type magnetic holding device for being equiped with miniature ultrasonic transducer units, relying on electromagnetism adhesive strength Socket is positioned at the close position of its terminal of the micro-fluidic chip, and, higher-order of oscillation electric signal transmission cable, the high frequency One end of vibration electric signal transmission cable links together with the miniature ultrasonic transducer units;The chain ring type magnetic holding device provides one The individual function of facilitating the device to disassemble;Its major function of the miniature ultrasonic transducer units is in the actual sample introduction test of micro-fluidic chip When, utilize the sample introduction end and the distance between the terminal and the miniature ultrasonic transducer units installation position difference and its institute Between the difference on ultrasonic intensity experienced, its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension Difference, the interfacial tension difference between the micro-fluidic chip both ends can form pressure between the both ends of the micro-fluidic chip Difference, the pressure gap can drive sample solution to the end flow;The dimethyl silicone polymer material that is soft and having elasticity Substrate its function include, with its property to the strong absorption of ultrasonic wave, absorbing ultrasonic wave strongly, and thereby in the miniflow Control chip terminal is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end;It is and many Silica dioxide granule, many silica dioxide granules are filled in the pipeline, and its tube chamber of the pipeline is by the two of many Silicon oxide particle is filled up, and its particle size range of the silica dioxide granule is between 10 microns and 200 microns, the silica Particle is silica crystalline particles, silica glass granule or silica composition its shared percentage by weight more than 80% Inorganic glass particles.
2. the readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function according to claim 1, its feature It is, the pipeline and the lateral and the manifold shape turnout are capillary channel.
3. the readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function according to claim 1, its feature It is, the thermal decomposition conducting polymer is the conductive material formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated.
4. the readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function according to claim 1, its feature Be, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the working electrode Length is between 1 micron to 15000 microns.
5. the readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function according to claim 1, its feature It is, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. the readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function according to claim 1, its feature It is, the cover plate its material in structure is dimethyl silicone polymer material.
7. the readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function according to claim 1, its feature Be, positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal this is remaining Air line distance between one liquid pool is between 3 centimetres and 7 centimetres;Described its thickness of cover plate and substrate in structure between Between 1.0 millimeters and 5.0 millimeters.
8. the readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function according to claim 1, 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 readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function according to claim 1, its feature Be, 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 The other end is connected with the higher-order of oscillation electric signal generator.
10. the readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function according to claim 1, its feature It is, for its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units between 5 milliwatts and 9000 milliwatts, this is miniature super The frequency of its ultrasonic wave operationally launched of acoustic wave transducer is between 100KHz and 12MHz.
CN201610356760.5A 2016-05-13 2016-05-13 The readily removable controller used in syphilis diagnosis micro fluidic device removed of liquid stream driving building blocks of function Withdrawn CN107362838A (en)

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Application publication date: 20171121