CN107457011A - Detect a variety of hypotype swine flu dual drive CGCM micro flow control chip devices - Google Patents

Abstract

The present invention relates to one kind to detect a variety of hypotype swine flu dual drive CGCM micro flow control chip devices, belongs to analysis testing field.The substrate of hypotype swine flu diagnosis micro-fluidic chip is made using dimethyl silicone polymer i.e. PDMS that is cheap and easily processing, a series of problems be present.This case main points are, the selected PDMS with ecosystem surface of substrate, and its neighbor positions fixes installing miniature ultrasonic transducer units in the sample liquid stream terminal of the micro-fluidic chip, with driving force of the ultrasonic wave induced synthesis based on interfacial tension difference, its driving force couples running with Micropump simultaneously, collaboration drives test liquid to flow to terminal direction flowing, 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

Detect a variety of hypotype swine flu dual drive CGCM micro flow control chip devices

Technical field

The present invention relates to one kind to detect a variety of hypotype swine flu dual drive CGCM micro flow control chip devices, belongs to analysis test Field.

Background technology

Multichannel micro-fluidic hypotype swine flu diagnostic techniques background, may refer to the patent of invention such as CN 201110311127.1 Shen Please 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 to 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, as described above, the PDMS conduit inner surfaces are strongly hydrophobic, and targetedly surface chemical modification or surface chemistry Modification is difficult to persistently again, therefore, actually can only still belong to effective short-term in the surface state after the modification of its surface or surface modification Within use it；If having had been subjected to that ofer short duration period of validity, and still by force if use, due to surface state Bigger flow resistance is then already certainly existed using usual Micropump driving sample liquid stream close to hydrophobic state again, this Sample, just by increasing Micropump pump power and pumping pressure test liquid can only be forced to flow to target direction flowing, as described above, this Kind of PDMS material is soft, pumps sample liquid stream with too high, mechanical pumping pressure, will cause its sample introduction of the substrate Bubbling, expanded, distortion, deformation occur for the conduit that end includes sample introduction end near zone, also, under this high-pressure situations, Under the sample introduction end and its conduit of near zone and its periphery also easily stripping between generation substrate and cover plate, this situation, Sample solution flows in the crack for entering appearance of the stripping afterwards between the substrate and cover plate of formation everywhere, and this is actually resulted in The damage of the micro-fluidic chip；Certainly, it is not in place if surface modification or surface modification script, also result in of short duration There is said circumstances within the usual term of validity；In the case where carrying out liquid stream driving using additional Micropump merely, the above-mentioned problem All the time exist.As described above, if the pre actions such as any surface modification or surface modification were not done completely, then, The above-mentioned problem will be even more serious, even without conduit bubbling, expanded, distortion, change described in generation sample introduction end and its near zone The problems such as being peeled off between shape and substrate and cover plate, merely because the flow resistance is excessive, it be able to may not also be driven using high pressure Micropump Dynamic sample liquid stream is marched forward towards terminal side.

Fourth, 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, while solves the system addressed above The problem of row, also, the solution is applied to hypotype swine flu diagnosis multichannel micro-fluidic chip field, formed a kind of Multichannel micro-fluidic chip device is used in new hypotype swine flu diagnosis.

The present invention solves the technical problem by following scheme, and the device that the program provides is a kind of a variety of hypotype pig streams of detection Dual drive CGCM micro flow control chip device is used in sense, and the structure of the device includes multichannel micro-fluidic chip, the micro-fluidic chip Structure include being bonded to each other installing substrate and cover plate together, the substrate and cover plate are plate object or tablet, the base The channel structure via mould pressing process or etching technics formation is contained in that face towards the cover plate of piece, is bonded to each other installed in one The substrate risen has been built into the micro-fluidic chip containing pipeline configuration jointly with the cover plate, and the locations of structures of the pipeline is located at the base The juncture area that piece is bonded to each other with the cover plate, the both ends of the pipeline connect with the sample introduction end of the micro-fluidic chip and terminal respectively Connect, the sample introduction end is the injection end of the micro-fluidic chip sample solution, when the terminal is the micro-fluidic chip actual sample introduction test its The terminal that sample solution flows in chip, the terminal are located remotely from each other with the sample introduction end, and the distance between the terminal and the sample introduction end are situated between Between 3 centimetres and 10 centimetres, working electrode is sequentially equiped with diverse location in the pipeline and to electrode and reference Electrode, the working electrode are resisted by conductive electrode and the hypotype swine flu specificity that embedded being attached on the conductive electrode Former gold size sensitive membrane is formed, and the construction of the pipeline is in parallel construction, the pipeline in parallel construction by three laterals simultaneously Connection is formed, and the quantity of the working electrode is three, and the installation position of three working electrodes is located at three branched pipes respectively In road, and, the specific antigen in its top layer gold size sensitivity membrane structure of three working electrodes is that hypotype swine flu is resisted respectively Three kinds of hypotype swine flu antigenic substances of physical efficiency specific binding, three kinds of antigenic substances are hypotype swine flu specific antigen respectively H₁N₁、H₃N₂And H₁N₂, its material of the working electrode be gold material or thermal decomposition conducting polymer material, the working electrode Sheet or thread is presented in its pattern, and emphasis is that its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is former The surface of raw form, the surface of the primary form its be intended to refer to and do not pass through any surface chemical modification or any surface chemistry The surface of the primary form of the modified material, the structure of the device also include miniature ultrasonic transducer units, and, the higher-order of oscillation Electric signal transmission cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable link together, should Miniature ultrasonic transducer units are installed in the position of the cover plate of the micro-fluidic chip or the neighbouring terminal of substrate with attaching；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 Micropump, the Micropump are connected with the sample introduction end, the Micropump is Built-in Micropump or external Micropump；The function of the Micropump is to induce with the ultrasonic wave with the mechanicalness pumping strength of the Micropump The both ends between interfacial tension difference its caused driving force support mutually, adjust mutually, be mutually coupled, with association Mode with running pools one strength for driving test liquid to flow to the terminal direction flowing；Described its thickness of cover plate and substrate Between 1.0 millimeters and 5.0 millimeters；And many silica dioxide granules, many silica dioxide granule fillings In the pipeline, its tube chamber of the pipeline is filled up by many silica dioxide granules, its particle diameter model of the silica dioxide granule Enclose between 10 microns and 200 microns, the silica dioxide granule is silica crystalline particles, silica glass granule Or silica composition its inorganic glass particles of shared percentage by weight more than 80%.

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 Micropump one art-recognized meanings of itself are known for the professional in micro-fluidic chip field.

The Micropump both can be the Micropump of external form；The Micropump can also be done into or say inside the embedded micro-fluidic chip The Micropump of the built in version of its sample introduction end structure position or the sample introduction end Near-neighbor Structure position.

For example miniature piezoelectric pump of the Micropump, miniature peristaltic pump or miniature air driven pump.

The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and hypotype swine flu specific antibody solution uniformly, is used Point 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 membrane Specific antibody be horseradish peroxidase or glucose oxidase mark hypotype swine flu antibody, the gold size sensitive membrane It has been included as fixing above-mentioned each hypotype swine flu specific antibody and introducing complementary medium therein, the complementary medium is for example Chitosan, cellulose acetate, gelatin be therein a kind of or their mixture.

The pipeline in the microfluidic chip structure includes the lateral, and its internal diameter size may each be arbitrarily selected Size, still, for prepare liquid sample and the consideration of reagent loss etc. is reduced less as far as possible, the pipeline includes described Lateral preferably selects the passage of capillary level, and the passage of the capillary level implies that its internal diameter and the capillary on ordinary meaning The suitable passage of the internal diameter of pipe.The shape of cross section of its inner passage of capillary can be arbitrary shape, the cross section Shape is for example circular, oval, square, rectangle, bar shaped, naturally it is also possible to be arbitrarily exist bending it is linear, also, With the extension of pipeline, the shape of cross section of different parts can also allow to be different shapes the interior shape of the capillary. 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 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.

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 2 milliwatts and 2000 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.

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：

This case is flowed with dual drive coupling operating mode driving liquid stream in the capillary channel of the triple channel micro-fluidic chip, Three kinds of hypotype swine flu diagnostic antigens are detected respectively using multi-channel electrochemical analyzer device.

Detect corresponding three kinds of hypotypes swine flu antibody with three kinds of hypotype swine flu antigens, with three kinds of hypotype swine flu antibody come Corresponding three kinds of hypotypes swine flu antigen is detected, similarly, corresponding hypotype swine flu can be diagnosed；The principle of its foundation It is necessarily antigen, antibody and to be deposited in hypotype swine flu patient, and mutual Reversible binding, reversible conjugate is formed, because This, is detected antibody and is thereby diagnosed corresponding hypotype swine flu with antigen, with antibody go detect antigen and diagnosis it is corresponding Asia Type swine flu, diagnostic purpose can be reached.Certainly, its corresponding electrode sensitive decorative layer of different means is not technically It is identical.

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 dual drive coupling operating mode driving, various hypotype swine flus The hypotype pig for the corresponding horseradish peroxidase-labeled that antibody molecule is embedded by gold size sensitive membrane on electrode surface in each passage is flowed Feel specific antigen capture.

2nd, the hypotype swine flu specific antigen of horseradish peroxidase-labeled is formed with the hypotype swine flu antibody in blood serum sample Immune complex.

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 hypotype swine flu antibody.

Changed it is an advantage of the invention that installing miniature ultrasonic in its close position attaching of the terminal of the micro-fluidic chip 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 The difference that the interfacial tension is caused at both ends is stated, the pressure gap that this kind is formed by Ultrasonic Radiation itself is exactly one driving Strength from sample solution to the end flow, while it also and the driving force that is provided of Micropump intercouple, Collaboration, Above-mentioned two bursts of strength makes a concerted effort to drive sample liquid stream to flow to the terminal direction in the pipeline in the lump.

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.

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 pipeline for PDMS materials 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 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 Big silica dioxide granule filler, its particle being stuck by rheology can not both be moved easily, the particle of its huge particle diameter It can not more be swallowed up easily by the inner-walls of duct of PDMS materials, therefore, its from this respect is similar to surface chemical modification Seen on technique effect, its technique effect of this case, be form it is permanent, can not erase, can not consume, not be corroded, not by Hydrophilic surface reforming layer swallowing up, being not dissolved, it is just comparable to a kind of in its correlation of PDMS base materials in effect The permanent hydrophilic modifying superficial layer built on surface.

With the simultaneous Micropump of miniature ultrasonic transducer units in its structure of micro-fluidic chip, its function is, with the Micropump Interfacial tension difference its caused driving force for coming between the both ends of ultrasonic wave induction of mechanicalness pumping strength Support mutually, adjust mutually, be mutually coupled, one driving test liquid is pooled in a manner of Collaboration and flows to the terminal side To the strength of flowing；The presence of the Micropump so that its ultrasonic wave emissive porwer of the miniature ultrasonic transducer units can be allowed to appropriateness Reduce, this is particularly suitable for for the situation containing ultrasonic wave sensitive composition in detection object；And due to the miniature ultrasonic transducer units And its presence of radiated ultrasonic wave, the micro-fluidic chip its both ends interfacial tension can be induced and difference occur and thereby bring spy Other driving force for sample solution, meanwhile, due also to being filled with its pipeline of this case micro-fluidic chip with hydrophily The silica dioxide granule of matter, then, in the scenario above, its flow resistance in the pipeline of sample liquid stream is greatly reduced, phase Ying Di, its running resistance of the Micropump are greatly reduced, so, the Micropump just can with than relatively low pumping pressure to be directed to The pumping work of sample solution is stated, because mechanical pumping pressure is greatly reduced, therefore, in such a situation, just not The conduit of the sample introduction end and its near zone caused by Yi Fashengyin sample introductions end its mechanicalness pumping pressure of Micropump is excessive Between bubbling, expansion, deformation, distortion and the region substrate and cover plate the problems such as stripping etc.；This case dual drive coupling running Scheme and add for the sample fluid flow action it is handling, can allow for using ultrasonic intensity, ultrasonic wave frequency Rate, Micropump pump power, the Micropump multiple indexs of pumping pressure etc. come be directed to the flow rate of the flowing, flowing action including to Preceding flowing or pause flowing or acceleration flowing etc. flowing action carry out multi-parameter and accurately manipulated；As described above, the presence of the Micropump, Its ultrasonic wave emissive porwer of the miniature ultrasonic transducer units is enabled to be allowed to appropriate reduction, then, the feature additionally aids guarantor The working electrode its sensitive coating is protected, is allowed to from ultrasound injury.

Based on this case scheme, repaiied completely without the surface chemistry carried out for the dimethyl silicone polymer substrate its relevant surfaces Decorations or surface chemical modification operation, therefore, this surface chemical modification layer or surface chemical modification layer not need to exist, So, its body phase interior polymer molecule of the dimethyl silicone polymer substrate is constantly diffused to the surface, migrated caused by it automatically The damaging influence of the surface chemical modification layer or surface chemical modification layer is also just not present.

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, very cheap and easily processing and fabricating the polydimethyl siloxane material of this kind just has can Can in the micro-fluidic chip its prepare, production, using etc. field play bigger effect.

Brief description of the drawings

Fig. 1 is its rough outside side view of this case device.

In figure, 1 is the substrate of dimethyl silicone polymer material, and 2 be cover plate, and 3 be higher-order of oscillation electric signal transmission cable, 4 It is miniature ultrasonic transducer units, 5 be the sample introduction end of the micro-fluidic chip, and 6 be the terminal of the micro-fluidic chip, 7 It is Micropump, 8 be infusion tube；Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends Difference driving, the flow direction of its sample liquid stream.

Embodiment

In this case that Fig. 1 is shown embodiment, the structure of the device includes multichannel micro-fluidic chip, the micro-fluidic core The structure of piece includes being bonded to each other the substrate 1 and cover plate 2 of installing together, and the substrate 1 and cover plate 2 are plate object or piece The channel structure via mould pressing process or etching technics formation, phase are contained in shape thing, that face towards the cover plate 2 of the substrate 1 The substrate 1 being mutually jointly mounted to together has been built into the micro-fluidic chip containing pipeline configuration jointly with the cover plate 2, the pipeline Locations of structures be located at the juncture area that the substrate 1 and the cover plate 2 are bonded to each other, the both ends of the pipeline respectively with the micro-fluidic core The sample introduction end 5 of piece and terminal 6 connect, and the sample introduction end 5 is the injection end of the micro-fluidic chip sample solution, and the terminal 6 is The terminal that sample solution flows in its chip when the actual sample introduction of the micro-fluidic chip is tested, the terminal 6 and the sample introduction end 5 are mutually remote From the distance between the terminal 6 and the sample introduction end 5 are between 3 centimetres and 10 centimetres, in the pipeline on diverse location Sequentially it is equiped with working electrode and to electrode and reference electrode, the working electrode is by conductive electrode and is attached to this and leads The gold size sensitive membrane for having embedded hypotype swine flu specific antigen on conductive electrodes is formed, and the construction of the pipeline is in parallel construction, The pipeline in parallel construction is made up of three lateral parallel connections, and the quantity of the working electrode is three, this three work The installation position of electrode is located in three laterals respectively, and, its top layer gold size sensitive membrane knot of three working electrodes Specific antigen in structure is the three kinds of hypotype swine flu antigenic substances that can be specifically bound to hypotype swine flu antibody respectively, and this three Kind antigenic substance is hypotype swine flu specific antigen H respectively₁N₁、H₃N₂And H₁N₂, its material of the working electrode is gold material Or sheet or thread is presented in thermal decomposition conducting polymer material, the working electrode its pattern, emphasis is, its material of the substrate 1 Dimethyl silicone polymer material, its surface of substrate 1 is the surface of primary form, the surface of the primary form its be meant to It is not by any surface chemical modification or the surface of the primary form of the material of any surface chemical modification, the knot of the device Structure also includes miniature ultrasonic transducer units 4, and, higher-order of oscillation electric signal transmission cable 3, higher-order of oscillation electric signal transmission One end of cable 3 links together with the miniature ultrasonic transducer units 4, and the miniature ultrasonic transducer units 4 are installed in this with attaching The position of the cover plate 2 of micro-fluidic chip or the neighbouring terminal 6 of substrate 1；Its main work(of the miniature ultrasonic transducer units 4 It can be in the actual sample introduction test of micro-fluidic chip, utilize the sample introduction end 5 and the terminal 6 and the miniature ultrasonic transducing Difference in the distance between the installation position of device 4 difference and its ultrasonic intensity experienced, sample introduction end described in induced synthesis Difference between 5 its interfacial tension and the terminal 6 its interfacial tension, the interface between the micro-fluidic chip both ends 5,6 Tension difference can form pressure gap between the both ends 5,6 of the micro-fluidic chip, and the pressure gap can drive sample solution Flowed to the direction of terminal 6；Softness simultaneously has its function of the substrate 1 of the dimethyl silicone polymer material of elasticity including right with its The property that ultrasonic wave absorbs strongly, ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic chip, the terminal 6 arrives the sample introduction The rapid decrement of ultrasonic intensity is realized within limited short distance between end 5；And Micropump 7, the Micropump 7 enter with this Sample end 5 connects；The function of the Micropump 7 is to carry out described two with ultrasonic wave induction with the mechanicalness pumping strength of the Micropump 7 Interfacial tension difference its caused driving force between end 5,6 is supported mutually, adjusts mutually, is mutually coupled, with collaboration The mode of running pools the strength that one driving test liquid flows to the direction of terminal 6 flowing；The cover plate 2 and substrate 1 Its thickness is between 1.0 millimeters and 5.0 millimeters；And many silica dioxide granules, many silica Grain be filled in the pipeline, its tube chamber of the pipeline is filled up by many silica dioxide granules, the silica dioxide granule its For particle size range between 10 microns and 200 microns, the silica dioxide granule is silica crystalline particles, silica glass Glass particle or silica composition its inorganic glass particles of shared percentage by weight more than 80%.

Arrow in legend indicate the micro-fluidic chip its in actual motion, by both ends 5,6 pressure differentials drive, its try The flow direction of sample liquid stream.

Fig. 1 is depicted without the associate members such as the higher-order of oscillation electric signal generator.

Involved miniature ultrasonic transducer units 4 are commercially available；It can also be customized to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal transmission cable 3 is commercially available；It can also be customized to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；It can also be customized to relevant manufacturers.

Micropump 7 involved by legend can customize to specialized factory.

Its connected mode with various micro-fluidic chip of various Micropump is known.

Its inner passage of the micro-fluidic chip involved by this case is the pipeline of hydrophobic capillary form.

The Micropump both can be the Micropump of external form；The Micropump can also be done into or say inside the embedded micro-fluidic chip The Micropump of the built in version of its sample introduction end structure position or the sample introduction end Near-neighbor Structure position, its basic structure key element and external form Micropump it is identical.Micropump in legend is the Micropump of external form.

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 (1)

1. a variety of hypotype swine flu dual drive CGCM micro flow control chip devices of detection, the structure of the device is micro- including multichannel Fluidic chip, the structure of the micro-fluidic chip include being bonded to each other the substrate and cover plate of installing together, and the substrate and cover plate are equal For plate object or tablet, the conduit via mould pressing process or etching technics formation is contained in that face towards the cover plate of the substrate Structure, it is bonded to each other the substrate being installed together and has been built into the micro-fluidic chip containing pipeline configuration jointly with the cover plate, should The locations of structures of pipeline is located at the juncture area that the substrate and the cover plate are bonded to each other, the both ends of the pipeline respectively with the micro-fluidic core The sample introduction end of piece and terminal connection, the sample introduction end is the injection end of the micro-fluidic chip sample solution, and the terminal is that this is micro-fluidic During the test of chip actual sample introduction in its chip sample solution flowing terminal, the terminal is located remotely from each other with the sample introduction end, the terminal and The distance between the sample introduction end is sequentially equiped with work electricity between 3 centimetres and 10 centimetres in the pipeline on diverse location Pole and to electrode and reference electrode, the working electrode is by conductive electrode and the embedding being attached on the conductive electrode The gold size sensitive membrane of hypotype swine flu specific antigen is formed, and the construction of the pipeline be in parallel construction, and described is in parallel construction Pipeline is made up of three lateral parallel connections, and the quantity of the working electrode is three, the installation position point of three working electrodes Not Wei Yu in three laterals, and, the specific antigen in its top layer gold size sensitivity membrane structure of three working electrodes It is the three kinds of hypotype swine flu antigenic substances that can be specifically bound to hypotype swine flu antibody respectively, three kinds of antigenic substances are respectively Hypotype swine flu specific antigen H₁N₁、H₃N₂And H₁N₂, its material of the working electrode is gold material or thermal decomposition conductive polymer Sheet or thread is presented in sub- material, its pattern of the working electrode, it is characterised in that its material of the substrate is polydimethylsiloxanes Alkane material, its surface of the substrate are the surfaces of primary form, the surface of the primary form its be intended to refer to and do not pass through any table The surface of the primary form of the material of face chemical modification or any surface chemical modification, the structure of the device also include miniature ultrasonic Wave transducer, and, higher-order of oscillation electric signal transmission cable, one end of the higher-order of oscillation electric signal transmission cable is miniature super with this Acoustic wave transducer links together, and the miniature ultrasonic transducer units are installed in cover plate or the neighbour of substrate of the micro-fluidic chip with attaching The position of the nearly terminal；Its major function of the miniature ultrasonic transducer units is in the actual sample introduction test of micro-fluidic chip, is utilized The distance between the sample introduction end and the terminal and miniature ultrasonic transducer units installation position difference and its experienced Ultrasonic intensity on difference, the difference between its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension Different, the interfacial tension difference between the micro-fluidic chip both ends can form pressure differential between the both ends of the micro-fluidic chip Different, the pressure gap can drive sample solution to the end flow；The dimethyl silicone polymer material that is soft and having elasticity Its function of substrate includes, with its property to the strong absorption of ultrasonic wave, absorbing ultrasonic wave strongly, and thereby micro-fluidic at this The chip terminal is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end；And Micropump, The Micropump is connected with the sample introduction end, and the Micropump is built-in Micropump or external Micropump；The function of the Micropump is, with the Micropump Interfacial tension difference its caused driving force that mechanicalness pumping strength is come between the both ends of ultrasonic wave induction is mutual Mutually support, adjust mutually, be mutually coupled, one driving test liquid is pooled in a manner of Collaboration and flows to the terminal direction The strength of flowing；Described its thickness of cover plate and substrate is between 1.0 millimeters and 5.0 millimeters；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.