Background technology
Multichannel micro-fluidic hypotype swine flu diagnostic techniques background, may refer to the patent of invention such as CN 201110311127.1 ShenPlease 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 agoMonograph " diagram Microfluid based Lab on a chip ", the monograph is published via Science Press, and the monograph is to microflow control techniquePast, 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 substrateOn 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 conduitInto described fluid course；So, it is clear that assemble the fluid course after completing, the main portion of its inner surface areaPoint 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 toThe integrality or property in road；Therefore say, the inner surface state or inner surface property of this conduit of the structure on substrate are crucialFactor；In principle, any material that can be kept or keep its solid forms substantially, can be used to make substrate and lidPiece, 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 polymerRadical 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 materialsNot 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, soSubstrate 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, seeminglyIt 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 toPopularization, 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 strongHydrophobic material, conduit is built on this material, if without being operated for the modified of the conduit surface, then, it is overallAfter assembling is completed, that is, after covering cover plate, because the conduit its inner surface in structure is occupied in most fluid courseSurface, then, its strong hydrophobic property of the PDMS conduits inner surface, is deciding factor, and it can be similar to water-solubleThe 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, existingAmong 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 expandedDissipate, the characteristic of migration, the characteristic that PDMS polymer molecules are diffused to the surface, migrated automatically inside this substrate body phase, will makeThe 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, thatHolding time for conduit its inner surface state after surface-modified is substantially only sufficient to the time for completing laboratory internal test experimentsNeed；In other words, by surface is modified or the PDMS conduit inner surfaces of surface modification, after it is modified or modification is saidThe 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 energyEnough a large amount of making, mass storages, it is widely popularized, answer is it is obvious that is, impossible.On this PDMS materialConduit, 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 cannotUse；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, withJust 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 solutionCombination occurs for composition so that tested composition can not be detected normally or it is detected ratio and dubiously reduced；Live on the surfaceProperty agent is possibly even fully wrapped around by tested composition with micelle form so that tested composition can not be detected or identify；Therefore, shouldKind 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 releasedDecorating 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 areaThe 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 hydrophobicMaterial surface and also another problem, that is, this strong hydrophobic PDMS surfaces can adsorb large biological molecule, andAnd these adsorbed large biological molecules can also further depression further on PDMS surfaces, gradually fall into it is gradually deep, directlyIt is trapped within the body phase of PDMS substrates to heavy, in fact, this process, is partly also due to inside PDMS material body phasePolymer 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 byGradually those are involved within the body phase of PDMS substrates by the large biological molecule of adsorption, briefly, these are inhaledAttached large biological molecule is exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up large biological moleculePhenomenon, 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, noIt 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, separatelyIt 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, depressionInto these Minute pores, and then swallowed up；However, inventor thinks, those can allow the air point of miniature scaleSon 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, twoPerson's difference on yardstick is huge, must not make sweeping generalizations.Explanation is bypassed, in any case, the biology as dependence test analysis objectMacromolecular is adsorbed by PDMS substrate conduits inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is known objective depositsPhenomenon.
, can be from containment PDMS surfaces to life in order to prevent swallow up effect of this PDMS substrate bodies relative to large biological moleculeThe absorption of thing macromolecular addresses, and method is chemically modified modification aiming at the PDMS material surface, forFor PDMS is the situation of substrate material, modification exactly is chemically modified to the surface of described channel portion, by chemistryThe conduit inner surface of modification, can contain its absorption to large biological molecule, and then avoid large biological molecule quiltPDMS substrate body phases are swallowed up；But or that old problem, that is, the chemical modification on PDMS material surface changesSurface 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 hydrophobicAnd 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 basesIts 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 reachesGrowth stage contains the absorption process of the PDMS substrate conduit inner surfaces to large biological molecule, and then prevents PDMS substrate bodies relativeThe 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 abovePersonnel 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 possibleAlso 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, itsThe polymer molecule of low polymerization degree inside body phase is in constantly into the dynamic process of surface migration, therefore, includes PDMS basesAfter 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 materialMigrate disconnectedly, pour into the surface and change, the change of its pattern is somewhat similarly to Rheological Deformation, trickling deformation or deformation of creep institutePattern changes caused by possible；In the higher PDMS material of some low polymerization degree component ratios, this kind is somewhat similarly to flowThe 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 substratesThe dynamic of inner-walls of duct surface topography afterwards changes property, namely the described property for being somewhat similarly to Rheological Deformation or trickling deformationProperty 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 ownThe certain Rheological Deformation property as described above having, its manufactured goods actually can at leisure Rheological Deformation and cause the manufactured goods wholeIndividual 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 advanceThe fluid course namely the pipeline formed when first making, because the wall of its tube chamber of pipeline is mainly PDMS materialsWall, 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 throughNarrow, 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 causedSample fluid course is thoroughly blocked, the journey for closing or fully closing with being even also not reaching to its luminal part of pipelineDegree, its fluid passage that can be provided of that pipeline narrow because of rheology, then, in pipeline, its inner surface is exactly originally strongIt 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 pipelineLong-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 totallyA series of problems, also, the solution is applied to hypotype swine flu diagnosis multichannel micro-fluidic chip field, form oneMultichannel micro-fluidic device is used in the new hypotype swine flu diagnosis of kind.
The present invention solves the technical problem by following scheme, and the device that the program provides is that one kind of multiple hypotype swine flus are sameWhen the multichannel micro-fluidic chip device that detects, the structure of the micro fluidic device includes multichannel micro-fluidic chip, the micro-fluidic coreThe structure of piece includes being bonded to each other the substrate and cover plate of installing together, and the substrate and cover plate are plate object or tablet, are somebody's turn to doThat face towards the cover plate of substrate contain via mould pressing process or etching technics formation channel structure, the substrate also contain withThe channel structure is connected and pierces the window knot formed via mould pressing process, etching technics or simple drilling technology of the substrateStructure, 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 plateThe 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 itsSide 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 poolQuantity 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 poolStructure 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 mutualIt 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 endThe 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 joinIt is logical, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode and reference electrode is describedWorking electrode is by conductive electrode and the gold size for having embedded hypotype swine flu specific antibody being attached on the conductive electrodeSensitive membrane is formed, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of three lateral parallel connections,The quantity of the working electrode is three, and the installation position of three working electrodes is located in three laterals respectively, withAnd the specific antibody in three working electrodes its top layer gold size sensitivity membrane structures be respectively can be special to hypotype swine flu antigenProperty combine three kinds of hypotype swine flu antibody materials, three kinds of antibody materials are hypotype swine flu specific antibody H respectively1N1、H3N2And H1N2, its material of the working electrode is gold material or thermally decomposes conducting polymer material, and its pattern of the working electrode is inExisting sheet or thread, emphasis is that its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is primary formSurface, the surface of the primary form its be intended to refer to not by any surface chemical modification or any surface chemical modification shouldThe surface of the primary form of material, the structure of the micro fluidic device also include miniature ultrasonic transducer units, and, higher-order of oscillation electricitySignal transmission cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable link together, and this is micro-Type ultrasonic transducer is installed in the position of the cover plate of the micro-fluidic chip or the neighbouring terminal of substrate with attaching；This is miniature superIts major function of acoustic wave transducer is in the actual sample introduction test of micro-fluidic chip, using the sample introduction end and the terminal with being somebody's turn to doDifference in the distance between miniature ultrasonic transducer units installation position difference and its ultrasonic intensity experienced, induce shapeDifference between described its interfacial tension of sample introduction end and the terminal its interfacial tension, the boundary between the micro-fluidic chip both endsFace tension difference can form pressure gap between the both ends of the micro-fluidic chip, and the pressure gap can drive sample solution to instituteState end flow；It is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and include with it to the strong suction of ultrasonic waveThe property of receipts, ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic chip terminal to limited between the sample introduction endThe rapid decrement of ultrasonic intensity is realized within short distance；And many silica dioxide granules, many silicaGrain be filled in the pipeline, its tube chamber of the pipeline is filled up by many silica dioxide granules, the silica dioxide granule itsFor particle size range between 10 microns and 200 microns, the silica dioxide granule is silica crystalline particles, silica glassGlass 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 designatedParticle 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, cuboidShape 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-mentionedInternal 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 gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and hypotype swine flu specific antibody solution uniformly, is usedPoint sample instrument point sample is coated on specified structure position, and forms its drying and forming-film.Hypotype swine flu in the gold size sensitive membraneSpecific antibody be horseradish peroxidase or glucose oxidase mark hypotype swine flu antibody, the gold size sensitive membraneIt has been included as fixing above-mentioned each hypotype swine flu specific antibody and introducing complementary medium therein, the complementary medium is for exampleChitosan, 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, its internal diameter chiIt 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 turnoutPassage imply that its internal diameter passage suitable with the internal diameter of the capillary on ordinary meaning.Its inner passage of capillary it is transversalFace shape can be arbitrary shape, the shape of cross section is for example circular, oval, square, rectangle, bar shaped, certainlyCan the linear of bending arbitrarily be present, also, the interior shape of the capillary is with the extension of pipeline, different partsShape 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 choosingFixed shape, the arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..It is described to electricityThe 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 storageMake, its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, the cavity shape such as cylindrical emptyCavity-like, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..The size of the liquid pool can be arbitrarily selectedSize, 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 possibleThe 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 fieldKnow.
Various sizes, variously-shaped ultrasonic transducer are commercially available；Commercially available miniature ultrasonic transducer units its sizes can be withIt 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 andSpeech, 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；EquallyGround, 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 electricityIts 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 isIt 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 2 milliwatts and 2000 milliwatts itBetween；The preferred scope of the frequency of its ultrasonic wave operationally launched of the miniature ultrasonic transducer units be between 100KHz withBetween 12MHz.
This case device can further include some annexes, the annex such as multiple tracks electrochemical workstation etc., institute certainlyThe 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 phaseThe 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-valveMeasure 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-valveThe 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 toOr say preferable its scope of the diameter between 0.1 micron to 2000 microns；The length of the working electrode can permitPermitted 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 micronTo 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 quickFeel film, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness, still, push awayPreferable 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, glassGlass, polymethyl methacrylate, dimethyl silicone polymer, etc., in order to make smaller size of micro-fluidic chip, for example doInto 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 waveExtremely fast decay, can preferably dimethyl silicone polymer be used as cover plate.Certainly, selected on large-sized micro-fluidic chipUsing 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 remainingAir line distance between one liquid pool can be arbitrarily selected suitable distance as needed, and still, the preferred value of the distance isBetween 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 preferablyThickness 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 chipIn, 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 liquidStream flows in the capillary channel of the triple channel micro-fluidic chip, using multi-channel electrochemical analyzer device respectively to three kinds of hypotypesSwine flu 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 hypotype swine flu antigen molecules are eachIn passage on electrode surface gold size sensitive membrane embed corresponding horseradish peroxidase-labeled hypotype swine flu specific antibodyCapture.
2nd, the hypotype swine flu specific antibody of horseradish peroxidase-labeled is formed with the hypotype swine flu antigen in blood serum sampleImmune complex.
3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, using the above-mentioned reaction of amperometric detectionCaused 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 hypotype swine flu antigen.
Changed it is an advantage of the invention that installing miniature ultrasonic in its close position attaching of the terminal of the micro-fluidic chipEnergy device, with the ultrasonic wave of miniature ultrasonic transducer units transmitting low-power, high-frequency band, meanwhile, utilize dimethyl silicone polymerIts strong absorbability to ultrasonic wave of substrate, in shorter distance, it is, from the terminal to the sample introduction end itBetween only several centimeters yardsticks very short distance in, reach the rapid decrement of ultrasonic intensity, thereby in the institute of the micro-fluidic chipState 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 twoPressure gap between end, driving sample liquid stream flow in the pipeline to the terminal direction.By this case liquid stream driving sideCase, 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 inSilica 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 granuleFill 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 andNarrow, 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 timeRaw serious deformation.
Numerous silica dioxide granule entities are mutually banked up under this case framework together at random in the pipeline, the silicaThe function of grain filler, also includes with the hydrophilic surface of its silica dioxide granule, utilizes each adjacent silicon dioxide particle certainlyMutual formed complications are continuous and its inner surface that is mutually close together by water-wetted surface has the sky of hydrophilic nmatureGap, in the hydrophilic fluid channel of the pipeline Inner Constitution network morphology, the having all the time although this complications can be continuousThe 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 complicationsIts presence of continuous hydrophilic fluid channel, counteracts its surface of the PDMS substrates of the primary form to a large extentThe flow resistance for liquid sample caused by strong hydrophobic property；In other words, because of liquid sample its account for maximum ratio intoIt 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 significantlyOvercome 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 dioxideThe rigid of silicon grain filler ties up, on lumen wall wall still can also be exposed its face of the surface of part hydrophobic propertyProduct is already dramatically reduced, and the area on its still exposed part surface for belonging to hydrophobic property does not have far smaller thanThe wall surface area of the hydrophobic property of the lumen wall wall in the presence of silica dioxide granule filler；So, at thisUnder 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 pipelineInside tube chamber, its interfacial tension between sample solution of the part surface of remaining hydrophobic property, plus that of hydrophilic nmatureNewly-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 withInterfacial 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 sampleLiquid 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 drivesSample 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 pipelineThe silica dioxide granule filler, can gradually by constantly Rheological Deformation and to arest neighbors free space promote PDMSThe pipeline wall of material more tightly wraps up, and this process eventually causes those part dioxies for pressing close to the lumen wall wallSilicon 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 partThe silica dioxide granule banked up with being mutually closely packed together each other incarceration together, due to this reason, the titanium dioxideSilicon grain filler just will not move in the pipeline easily, and silica dioxide granule therein, which is also substantially all, is locked in originalLocate, 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 generalFor 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, byIn 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 compatibleOr 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 materialsFace 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 diameterSilicon grain surely not be fully sunk in easily or sink to completely PDMS materials its among intrinsic many Minute pores, andAnd 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 embeddingIn 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 wallIts area of the surface of part hydrophobic property be already dramatically reduced, its still exposed part for belonging to hydrophobic propertyThe area on surface be far smaller than no silica dioxide granule filler in the presence of the lumen wall wall dredgeThe 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, graduallyGround is partially embedded into or is partly absorbed among the lumen wall wall, its direction pipe of the silica dioxide granule among the stateThe 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 chamberThe 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 actuallyIt 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 pipelineSample solution large biological molecule therein and organic molecule produce suction-operated.Based on above-mentioned mechanism, then because filling up describedIts presence of the silica dioxide granule filler of pipeline, the overwhelming majority of its lumen wall wall of the pipeline are tightly hiddenLid, these described walls tightly covered can not contact with flowing through the sample solution of the pipeline, be only remainderThe 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 solutionTouch, in other words, under this case framework, large biological molecule and organic molecule in sample solution its with hydrophobic PDMS wallsDirect touch opportunity significantly reduce, thus, the lumen wall faces of PDMS materials its to large biological molecule and organic moleculeAdsorptive hindrance and swallow up interference be greatly reduced；As described above, this case scheme is advantageous to exclude or weakens the absorptionInterference 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 materialsRoad 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 materialsBy the surface modification of hydrophobic property into the surface of hydrophilic nmature, still, with general, usual PDMS surface chemical modifications itsThe 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 hugeSilica dioxide granule filler, its particle being stuck by rheology can not both be moved easily, and the particle of its huge particle diameter is moreIt 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 modificationSeen 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 effectThe 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 systemRow technical barrier.Based on this case scheme, the very cheap polydimethyl siloxane material of this kind is just possible in micro-fluidic chip systemStandby, production, using etc. field play bigger effect.