CN107335481A - The special cheap AIDS diagnosis micro fluidic device in fluid passage - Google Patents

Abstract

The present invention relates to a kind of special cheap AIDS diagnosis micro fluidic device in fluid passage, belong to analysis testing field.With dimethyl silicone polymer i.e. PDMS that is cheap and easily processing to make AIDS diagnosis with the substrate of micro-fluidic chip be a technical goal；The PDMS has spontaneous slow deformation properties, and the spontaneous slowly deformation properties can cause its pipeline of chip to become narrow gradually, and PDMS surfaces are strongly hydrophobic, and surface chemical modification modified effect is difficult to persistently, its surface and can also adsorb, swallow up large biological molecule.This case main points are that substrate material is the PDMS for having ecosystem surface, and micron silica particle is filled with its pipeline of chip；Its function of the micron silica granule filler includes supporting pipeline inwall, and, with the set of hydrophily fluid channel come the hydrophobic pipeline of compensatory script, and, by hard squeeze, cover the chance for thereby reducing large biological molecule and being contacted with the internal face in inner-walls of duct face.

Description

The special cheap AIDS diagnosis micro fluidic device in fluid passage

Technical field

The present invention relates to a kind of special cheap AIDS diagnosis micro fluidic device in fluid passage, the micro fluidic device It is that analysis testing field is belonged to come the special purpose device of diagnosis of aids based on antigen/antibody specific reaction.

Background technology

The micro-fluidic AIDS diagnosis technical background of associated multi-channel, it is special to may refer to the grade inventions of CN 200910151219.0 Sharp application case.

Only for the microflow control technique overall general picture of itself, famous micro-fluidic expert Mr. Lin Ping Cheng may refer to not The monograph " diagram Microfluid based Lab on a chip " gone out before long, the monograph is published via Science Press, and the monograph is to micro-fluidic Past of technology, now, and, vision of the future etc. etc., suffer from detail, be deep into long discussion of detail.

So, the Important Problems of this case that to have a talk below concern.

The basic framework of micro-fluidic chip, including it is etched with the substrate of conduit and the cover plate to fit together therewith, institute State the fluid course on substrate, before upper cover plate is assembled, it is apparent on see to be exactly some conduits, wait until lid is covered thereon After piece, just really closure forms the fluid course, and the conduit inner surface of the conduit is together with the part that surround the conduit Cover plate forms described fluid course together；So, it is clear that assemble the fluid course after completing, its inner surface face Long-pending major part is the inner surface area of that conduit, and in other words, the state or property of the conduit inner surface are substantially determined The integrality or property of the fluid course are determined；Therefore say, the inner surface state or interior of this conduit of the structure on substrate Surface nature is key factor；In principle, any material that can be kept or keep its solid forms substantially, can be used To make substrate and cover plate, such as, the material that can act as substrate and cover plate can be monocrystalline silicon piece, quartz plate, sheet glass, height Polymers such as dimethyl silicone polymer, polymethyl methacrylate, makrolon etc.；Certainly, the selection of substrate and the choosing of cover plate Material be able to can also be differed with identical；From the point of view of material consumption, manufacture difficulty and application popularization prospect etc. etc., these Not small difference, the especially selection of that substrate between material be present, have a great influence.

In various substrate making materials, dimethyl silicone polymer, i.e. PDMS, comparatively very easily shaping, at this It is extremely simple that conduit is made on the substrate of sample, and the lower cost for material, substrate is made with the polydimethyl siloxane material, Conduit is being suppressed or etched thereon, and is being engaged with the cover plate that the cheap material such as glass or polypropylene or other plastic sheets makes, It is a kind of more satisfactory selection seemingly；Certainly, patch material can also select to use cheap polydimethyl siloxane material： So, this substrate selection is the scheme of polydimethyl siloxane material, and material is extremely cheap, and making is extremely simple, seems and should also be as It is extremely easy to popularize, promotes.

But thing is really not so simple.

First, this polydimethyl siloxane material, that is, the material that alphabetical PDMS is referred to of abridging, itself are a kind of strong Strong hydrophobic material, conduit is built on this material, if without being operated for the modified of the conduit surface, then, it is whole After body assembling is completed, that is, after covering cover plate, because the conduit its inner surface in structure occupies most fluid course Inner surface, then, its strong hydrophobic property of the PDMS conduits inner surface, is deciding factor, it can be similar to water The fine liquid stream of polar liquid of solution by becoming very difficult, its flow resistance is big, or even in general Micropump is all difficult to Promote, certainly, if cover plate also selects to use the PDMS material, then, problem is substantially identical, similar；Therefore, existing Among having technology, modification is modified particular for the conduit inner surface on the PDMS material, is necessary operation；So, this The individual modified operation for PDMS conduit inner surfaces is pretty troublesomeThat falls nor this problem, forms serious technical puzzlement, It is another problem：PDMS polymer molecules inside its body phase of this PDMS material substrate have to be diffused to the surface, moves automatically The characteristic of shifting, the characteristic that this substrate body phase inside PDMS polymer molecules are diffused to the surface, migrated automatically, will cause by table State after the modification of its inner surface of that conduit of face modifying and decorating can not maintain the sufficiently long time, and that is through surface Holding time for conduit its inner surface state after modification is substantially only sufficient to the time needs for completing laboratory internal test experiments； In other words, by surface is modified or the PDMS conduit inner surfaces of surface modification, after it is modified or institute's shape after modification is said Into surface state can not be lasting, but soon automatically tend to or say become again surface be modified before surface state, compared with The strong hydrophobic surface state of that script is returned in the short time, then, just think, such micro-fluidic chip can be big Amount making, mass storage, it is widely popularized, answer is it is obvious that is, impossible.Conduit on this PDMS material, does not do If surface modification, it can not pump and pass through similar to the fine liquid stream of polar solvent of the aqueous solution, chip also cannot just use；And such as Fruit has been cooked surface modification, can not persistently keep its state after modifying again, or equally can not popularization and application.

According to the literature, there is a kind of expedient solution, be that a small amount of surface-active is added in sample to be tested solution Agent, so as to which during test, dynamic, temporary transient effective surface hydrophilic layer is built temporarily in the PDMS conduits inner surface； However, due to the amphipathic characteristic of surfactant, the introduced surfactant of the program is inevitable simultaneously also can be with sample solution In tested composition occur combination so that tested composition can not be detected normally or it is detected ratio and dubiously dropped It is low；The surfactant is possibly even fully wrapped around by tested composition with micelle form so that tested composition can not be detected or Identification；Therefore, this kind adds the scheme of surfactant into sample solution, is far from a preferable solution.

So, how to accomplish that substrate can either be made using cheap PDMS material, and the conduit can be released Inner surface decorating state can not persistently, chip can not largely make, largely lay in and then be widely popularized and such a make this area The puzzlement that numerous professionals are entangled with for a long time, the highly difficult problem that exactly one its obvious technology barrier can not despise.

Be present many year in the highly difficult problem, so far, not yet properly settled.

Second, the PDMS material of non-surface modification, it is stated that, its surface is strongly hydrophobic above, this strong hydrophobic Material surface and also have another problem, that is, this strong hydrophobic PDMS surfaces can adsorb large biological molecule, and And these adsorbed large biological molecules can also further depression further on PDMS surfaces, gradually fall into it is gradually deep, until It is heavy to be trapped within the body phase of PDMS substrates, in fact, this process, partly it is also due to PDMS material body phase interior polymer Molecule, which has, to be diffused to the surface, caused by travel motion；Such case, it can also be explained from another angle, i.e. continue not Disconnectedly from inside PDMS body phases to those polymer molecules of its diffusion into the surface, migration, its result moved, be little by little by that It has been involved in a bit by the large biological molecule of adsorption within the body phase of PDMS substrates, briefly, these adsorbed biologies Macromolecular is exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up the phenomenon of large biological molecule, its institute Caused by influence, necessarily cause the severe deviations of all kinds of test data of experiment for being related to large biological molecule.

As described above, the problem of PDMS substrates, is, its not only adsorption large biological molecule, and swallow up biological big point Son, so, as the large biological molecule of experiment test object, its disappearance will not stop because surface saturation is adsorbed, and It is, it is constantly adsorbed, also constantly swallowed up.

On PDMS substrates, its body phase is constantly swallowed up and tests showing for associated biomolecule macromolecular in related experiment test process As, it is to say that another kind, which is explained, substantial amounts of Minute pores in PDMS body phases be present, associated biomolecule macromolecular by after adsorption, Depression enters these Minute pores, and then is swallowed up；However, inventor thinks, those can allow the sky of miniature scale Qi leel squeezes into the Minute pores therebetween, not equal to saying that they also can directly allow the large biological molecule of relative large scale to enter Enter, both difference on yardstick are huge, must not make sweeping generalizations.Explanation is bypassed, in any case, as dependence test analysis object Large biological molecule is adsorbed by PDMS substrate conduits inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is known objective Existing phenomenon.

, can be from containment PDMS surfaces pair in order to prevent swallow up effect of this PDMS substrate bodies relative to large biological molecule The absorption of large biological molecule addresses, and method is chemically modified modification aiming at the PDMS material surface, for For PDMS is the situation of substrate material, modification exactly is chemically modified to the surface of described channel portion, by chemistry The conduit inner surface of modification, can contain its absorption to large biological molecule, and then avoid large biological molecule quilt PDMS substrate body phases are swallowed up；But or that old problem, that is, the chemical modification on PDMS material surface is modified it Surface state afterwards can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface, migrate automatically Process, can soon by that by surface chemical modification be modified conduit inner surface state become again script it is strong it is hydrophobic simultaneously And the state of strong adsorption large biological molecule, in other words, no matter how professionals in the field turn from side to side, the PDMS substrates its Conduit inner surface is always rapidly to strong hydrophobic surface state evolution.

So, how can either obtain that PDMS material price is extremely cheap, substrate makes extremely easy benefit, and can is enough Reach and contain the absorption process of the PDMS substrate conduit inner surfaces to large biological molecule for a long time, and then prevent PDMS substrate bodies relative The effect of swallowing up of large biological molecule so that related chip manufactured goods are able to maintain that a prolonged enough, rational shelf-life, It is exactly a very intractable problem.The problem equally makes this area numerous specially as another problem addressed above Industry personnel are entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise.Should Also be present many year in problem, so far, also not yet properly settled.

Third, the polydimethyl siloxane material, namely PDMS material, the active force very little wherein between polymer molecule, The polymer molecule of low polymerization degree inside its body phase is in constantly into the dynamic process of surface migration, therefore, includes PDMS After it has been formed, the surface topography in its inner-walls of duct face of chip can be because of described low polymerization degree polymer point for the chip of substrate material Son moves about, pours into the surface and change, and the change of its pattern is somewhat similarly to Rheological Deformation, trickling deformation or creep and become Pattern caused by shape institute is possible changes；In the higher PDMS material of some low polymerization degree component ratios, this kind somewhat similar Can be showed in the phenomenon of Rheological Deformation, trickling deformation or the deformation of creep must be than more significant；This kind include PDMS substrates chip its The dynamic of inner-walls of duct surface topography after shaping changes property, namely the described property or stream that are somewhat similarly to Rheological Deformation Drop down the property of deformation or the property of the deformation of creep, this case applies mechanically the word of rheology one, integration, also referred to as the rheological equationm of state or rheology Deformation properties, the dynamic of corresponding inner-walls of duct face pattern change, and this case is also referred to as rheology；As described above, because of this kind Its own certain Rheological Deformation property as described above for having of material, its manufactured goods actually can at leisure Rheological Deformation and The manufactured goods total form generation is caused to change；Influence caused by its Rheological Deformation property, it is to be not easy in terms of macroscopic perspective Perceive, still, for the very fine micro-fluidic chip of its internal structure, the rheological equationm of state can but cause bigger Influence, the fluid course namely the pipeline therefore, during pre-production formed, because of the wall master of its tube chamber of pipeline If the wall of PDMS materials, so, the cross-sectional area of the pipeline actually can be gradual over time because of rheology Diminish, stated differently, since the reason for the rheology, the natively finer pipe that is flowed through for liquid sample Its tube chamber of road the more can become the more narrow, and in the case of flow time is sufficiently long, or even the tube chamber of the pipeline can be closed partly or entirely Close to portion, and then make it that sample fluid course is thoroughly blocked, with being even also not reaching to its luminal part of pipeline Closure or the degree fully closed, its fluid passage that can be provided of that pipeline narrow because of rheology, then, in pipe In the case that road its inner surface is exactly strongly hydrophobic originally, aqueous sample liquid is just more difficult to by becoming so because of rheology Narrower micro-channel, then, the influence of substrate rheology how is resisted, maintains the basic framework of the pipeline not occur seriously for a long time The problem of deformation, also, keep the long-term unobstructed of the pipeline is exactly a urgent need to resolve.

The content of the invention

The technical problem to be solved by the invention is to provide a package solution, solves totally above The problem for three aspects addressed, also, the solution is applied to AIDS diagnosis multichannel micro-fluidic chip field, Form a kind of new AIDS diagnosis multichannel micro-fluidic device.

The present invention solves the technical problem by following scheme, and the device that the program provides is that a kind of fluid passage is special Cheap AIDS diagnosis micro fluidic device, the structure of the micro fluidic device includes multichannel micro-fluidic chip, the miniflow The structure of control chip includes being bonded to each other the substrate and cover plate of installing together, and the substrate and cover plate are plate object or sheet The channel structure via mould pressing process or etching technics formation, the substrate are contained in thing, that face towards the cover plate of the substrate Also contain and be connected and pierce being formed via mould pressing process, etching technics or simple drilling technology for the substrate with the channel structure Window structure, be bonded to each other the substrate that is installed together and the cover plate and be built into jointly containing pipeline configuration and therewith The micro-fluidic chip of connected liquid pool structure, the locations of structures of the pipeline are located at the interface area that the substrate is bonded to each other with the cover plate Domain, its side of the window is blocked by the cover plate and opposite side opens, and the locations of structures of the window is exactly the structure bit of the liquid pool Put, the quantity of the liquid pool is three, and its locations of structures of two liquid pools therein is located at the sample introduction end of the micro-fluidic chip, remaining The liquid flowing in its chip when being located at the actual sample introduction test of the micro-fluidic chip of liquid pool its locations of structures terminal, the end End is located remotely from each other with the sample introduction end, and one end of the pipeline is via the manifold shape turnout for being similarly positioned in the interface zone being bonded to each other Respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline and the terminal positioned at the micro-fluidic chip A remaining liquid pool UNICOM, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electricity Pole and reference electrode, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded AIDS The gold size sensitive membrane of specific antibody is formed, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by four Lateral is in parallel to be formed, and the quantity of the working electrode is four, and the installation position of four working electrodes is located at institute respectively State in four laterals, and, the specific antibody in its top layer gold size sensitivity membrane structure of four working electrodes is respectively The four kinds of aids antibody materials that can be specifically bound to AIDS antigen, four kinds of antibody materials are aids antibody respectively P24 and aids antibody gp41 and aids antibody gp120 and aids antibody gp36, its material of the working electrode It is gold material or thermal decomposition conducting polymer material, sheet or thread is presented in its pattern of the working electrode, and, Micropump, The Micropump is connected with the sample introduction end of the micro-fluidic chip, and the Micropump is the Micropump of external form or the Micropump of built in version, is weighed Point is that its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, the primary form Surface its be intended to refer to the primary shape of the not material by any surface chemical modification or any surface chemical modification The surface of state；And many silica dioxide granules, many silica dioxide granules are filled in the pipeline, the pipe Its tube chamber of road is filled up by many silica dioxide granules, and its particle size range of the silica dioxide granule is between 10 microns and 200 Between micron, the silica dioxide granule is its institute of silica crystalline particles, silica glass granule or silica composition Account for inorganic glass particles of the 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 any The particle diameter specified, such as 10 microns, 30 microns, 70 microns, 100 microns, 150 microns or 200 microns of the particle diameter, etc..

The scope of further preferred its particle diameter of the silica dioxide granule is between 100 microns and 200 microns.

Its pattern of the silica dioxide granule is unlimited, and the silica dioxide granule for example can be spheric granules, rod-shaped particles, length Cube shape particle or any amorphous granular.

The various silica dioxide granules manufacturing technology of itself is known technology.

Various forms, the silica dioxide granule market of all size are on sale.

The silica dioxide granule can also customize to specialized factory.

The preferred scope of its internal diameter of pipeline is between 500 microns and 1000 microns；It is but excellent compared to above-mentioned The internal diameter of the pipeline scope of choosing, more tiny internal diameter of the pipeline or thicker internal diameter of the pipeline are also what this case was allowed.

The 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 do into or say the embedded micro-fluidic chip The Micropump of the built in version of internal its sample introduction end structure position or the sample introduction end Near-neighbor Structure position, its basic structure key element with it is outer The Micropump for putting form is identical.

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

Involved Micropump can customize to specialized factory.

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

Fluid course described in pipeline described in this case and this case, this two kinds to express its art-recognized meanings identical.

The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and AIDS specific antibody solution uniformly, is used Point sample instrument point sample is coated on specified structure position, and forms its drying and forming-film.AIDS in the gold size sensitive membrane is special Heterogenetic antibody is the aids antibody of horseradish peroxidase or glucose oxidase mark, and the gold size sensitive membrane has been wrapped Containing complementary medium therein is introduced for the above-mentioned each AIDS specific antibody of fixation, the complementary medium such as shell gathers Sugar, cellulose acetate, gelatin be therein a kind of or their mixture.

The pipeline and the lateral and the manifold shape turnout in the microfluidic chip structure, in it Footpath size may each be arbitrarily selected size, still, for as far as possible less with prepare liquid sample and reduction reagent loss etc. Consideration, the pipeline and the lateral and the manifold shape turnout preferably select capillary level passage, institute The passage for stating capillary level implies that its internal diameter passage suitable with the internal diameter of the capillary on ordinary meaning.The capillary is in it The shape of cross section of portion's passage can be arbitrary shape, and the shape of cross section is for example circular, oval, square, rectangle, bar Shape, naturally it is also possible to it is the linear of bending arbitrarily be present, also, the interior shape of the capillary is with the extension of pipeline, The shape of cross section of different parts can also allow to be different shapes.Only for the word of capillary one, its art-recognized meanings is public Know.

What is be related in structure is the electrode of microsize to electrode and reference electrode, and its electrode shape, which may each be, appoints The selected shape of meaning, the arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..It is described Art-recognized meanings to electrode and the reference electrode vocabulary of itself are known.

It is related to several liquid pools in this case microfluidic chip structure, the liquid pool is the pond shape or capsule for transitional liquid storage Shape constructs, and its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, and the cavity shape is for example round Cylindrical cavity shape, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..The size of the liquid pool can be any Selected size, still, in order to as far as possible less with prepare liquid sample and reduce reagent loss, the liquid pool be preferably capable of with The liquid pool of the microminiature of capillary matching.

Only with regard to naked PDMS substrates itself conduit molding or lithographic technique for, be open-and-shut known technology； Similarly, the technology of hole-opening is even more known simple technique on naked PDMS substrates.This case is not also to this expansion superfluous words.

This case device can further include some annexes certainly, and the annex is such as multiple tracks electrochemical workstation Deng the art-recognized meanings of the multiple tracks electrochemical workstation are known.The each work being related in this case microfluidic chip structure Electrode and to electrode and reference electrode etc., special it can get lines crossed and the multiple tracks electrochemical workstation via corresponding respectively The corresponding interface coupled.It is described that special to get lines crossed be for by each phase of each electrode and the multiple tracks electrochemical workstation Answer the private cable that interface is coupled to each other.The micro-fluidic chip in this case device, its structure can also include micro-valve, The quantity of the micro-valve is unlimited, and according to being actually needed, the micro-valve can be installed in any need in the microfluidic chip structure Position to be mounted；The word of micro-valve one is for the professional of micro fluidic chip technical field, the art-recognized meanings of itself It is known；The micro-valve itself manufacturing technology and the use of technology is also known；The component that the micro-valve is not required.

The diameter of the working electrode can allow to be that any setting is easily installed the suitable diameter used, still, It is recommending or say preferable its scope of the diameter between 0.1 micron to 2000 microns；The length of the working electrode can To allow to be that any setting is easily installed the length used, it is however recommended to or to say the preferable length its scope be 1 Micron is between 15000 microns.

It is installed in by spraying or point sample instrument point sample or the coating of other appropriate process described in the working electrode surface layer Gold size sensitive membrane, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness, It is however recommended to thickness preferable thickness is between 10 nanometers and 200 nanometers in other words.

The cover plate in chip structure, its material can allow to be any electrical insulating property material, such as：Polypropylene, Glass, polymethyl methacrylate, dimethyl silicone polymer, etc..Certainly, select to use on large-sized micro-fluidic chip Dimethyl silicone polymer is used as the cover plate, and this case technical scheme is allowed.

Positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal should Air line distance between a remaining liquid pool can be arbitrarily selected suitable distance, still, the distance as needed Preferred value is between 3 centimetres and 7 centimetres.

Described its thickness of cover plate and substrate can allow be any setting the thickness for being easy to assembling, the thickness of recommendation or say Preferable thickness is between 1.0 millimeters and 5.0 millimeters.Less thickness is advantageous to save material.

The application method of this case micro-fluidic chip：

This case is flowed with Micropump driving liquid stream in the capillary channel of the four-way micro-fluidic chip, utilizes four-way Road electrochemical analytical instrument is detected to four kinds of AIDS diagnosis antigens respectively.

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 Micropump driving, various AIDS antigen molecules are by each logical The AIDS specific antibody for the corresponding horseradish peroxidase-labeled that gold size sensitive membrane embeds captures on electrode surface in road.

2nd, the AIDS specific antibody of horseradish peroxidase-labeled is formed with the AIDS antigen in blood serum sample and exempted from Epidemic disease compound.

3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, it is above-mentioned using amperometric detection Curent change caused by reaction, it is derived from the species and content of various analytes.

4th, result is subjected to comprehensive analysis, comprehensive diagnos is carried out to AIDS antigen.

Advantages of the present invention：Its scheme of this case is by having time in addition to electrode installation takes up space in the pipeline Complementary space is all filled up with the silica dioxide granule.Those are filled in the silica dioxide granule in pipeline, and this case is to its entirety Abbreviation silica dioxide granule filler, its function include support, withstand the tube chamber of the pipeline its inwall so that the pipe of the pipeline Chamber prevents its reduced cross-sectional area of the tube chamber of the pipeline or even closed, so as to maintain for a long time from narrowing because of the rheology Serious deformation does not occur for the basic framework of the pipeline.

Numerous silica dioxide granule entities are mutually banked up under this case framework together at random in the pipeline, the titanium dioxide The function of silicon grain filler, also include certainly with the hydrophilic surface of its silica dioxide granule, utilize each adjacent titanium dioxide Mutual formed complications are continuous and its inner surface that is mutually close together by water-wetted surface of silicon grain has hydrophilic The space of property, in the hydrophilic fluid channel of the pipeline Inner Constitution network morphology, although this complications can be continuous All the time the fluid channel with hydrophilic nmature, then, inside the tube chamber of the pipeline simultaneously and a plurality of miniflow deposited The effect of its synthesis of road, integrated, cumulative superposition in other words, is the equal of the relatively fine hydrophilic capillary of caliber Passage；Its presence of the continuous hydrophilic fluid channel of the complications, the PDMS of the primary form is counteracted to a large extent The flow resistance for liquid sample caused by the strong hydrophobic property in its surface of substrate；In other words, because of liquid sample, it is accounted for The composition of maximum ratio is water, and liquid sample is substantially exactly the aqueous solution, therefore, the presence of the silica dioxide granule filler, Can significantly overcome with the unmodified PDMS substrates of hydrophobic property and surface its to the aqueous solution it is incompatible, repel and Barrier effect, so be greatly reduced belong to properties of Aqueous Solution sample liquid stream its be advanced through the resistance of pipeline.

Under this case framework, inside the tube chamber of the pipeline, the area of its lumen wall wall of former pipeline, because of described two The rigid of silicon oxide particle filler ties up, the table of part hydrophobic property that still can also be exposed on lumen wall wall Its area of face is already dramatically reduced, and the area on its still exposed part surface for belonging to hydrophobic property is much Less than the wall surface area of the hydrophobic property of the lumen wall wall in the presence of no silica dioxide granule filler； So, under this case framework, in its lumen of the pipeline, its remaining hydrophobic surface increases surface newly with hydrophilic part, and it is folded Adding, comprehensive, summation, cumulative technique effect, is to form the surface for tending to be hydrophilic on the whole；In other words, in institute State inside the tube chamber of pipeline, its interfacial tension between sample solution of the part surface of remaining hydrophobic property, plus parent The part of aqueous nature increases its interfacial tension between sample solution of surface newly, that it is superimposed, comprehensive, summation, cumulative Technique effect, be so that its solid-liquid interfacial tension inside the tube chamber of the pipeline synergy level off to capillary glass tube its Interfacial tension between tube chamber inner surface and sample solution.

Therefore, exist in the pipeline under this case framework for having stated silica dioxide granule filler, this case scheme is just Driving to sample liquid stream can be reached with relatively low Micropump pump power and relatively low Micropump pumping pressure.

On the other hand, due to its rheological equationms of state of 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 materials Pipeline wall more tightly wrap up, this process eventually causes those part titanium dioxides for pressing close to the lumen wall wall Silicon grain 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 dioxy Silicon carbide particle filler just will not move in the pipeline easily, and silica dioxide granule therein is also substantially all locked In original place, therefore the stream framework of the micro-fluidic chip can be kept for a long time.

The particle size range of its particle of this case silica dioxide granule filler between 10 microns and 200 microns, compared to For general organic molecule, general large biological molecule, the particle diameter of its particle of this case silica dioxide granule filler can be rated as huge It is big incomparable, due to its huge particle diameter, and the surface of its polarity and the inner surface of the pipeline of strong hydrophobic PDMS materials It mutually can not perhaps say and mutually melt, then, the huge silica dioxide granule of this kind of particle diameter can not be by the pipeline of PDMS materials Inner surface adsorbed, can not more be swallowed up by the inner surface of the pipeline of PDMS materials, this kind of particle diameter it is huge described two Silicon oxide particle surely not be fully sunk in easily or sink to completely PDMS materials its among intrinsic many Minute pores, And because above it is stated that the rheology the reason for, the silica dioxide granule filler can be stuck in original place in other words It is without moving easily embedded in original place.

Inside the tube chamber of the pipeline, its lumen wall wall of former pipeline is entirely the surface of hydrophobic property originally, such as Upper described, under this case framework, rigid because of the silica dioxide granule filler ties up, on lumen wall wall still also Its area of the surface of part hydrophobic property that can be exposed is already dramatically reduced, and it is still exposed to belong to hydrophobicity The area on the part surface of matter has been far smaller than the tube chamber in the presence of no silica dioxide granule filler The wall surface area of the hydrophobic property of inwall wall；The reason for because of the rheology, it is close to those dioxies of lumen wall wall Silicon carbide particle, little by little it is partially embedded into or is partly absorbed among the lumen wall wall, the dioxy among the state Silicon carbide particle its towards the part surface of lumen wall wall with have occurred and that matching deformation the lumen wall wall it is tight Closely connected conjunction, then, the matching is deformed and closely pasted with silica particles having occurred and that in lumen wall wall The part wall of conjunction actually can not contact with flowing through the sample solution of pipeline, that is to say, that the wall of this part is Through suction-operated can not be produced to the large biological molecule therein that flows through the sample solution of pipeline and organic molecule.Based on above-mentioned Mechanism, then because fill up the pipeline the silica dioxide granule filler its presence, its lumen wall wall of the pipeline The overwhelming majority in face is tightly covered, and these described walls tightly covered can not be with flowing through the pipeline Sample solution contact, only remaining fraction be not brought into close contact by its surface of silica dioxide granule, tightly cover Hydrophobic surface may be contacted with sample solution, in other words, under this case framework, large biological molecule in sample solution and have Its direct touch opportunity with hydrophobic PDMS walls of machine molecule is significantly reduced, thus, the lumen wall faces of PDMS materials its The adsorptive hindrance and interference of swallowing up of large biological molecule and organic molecule are greatly reduced；As described above, this case scheme Be advantageous to exclude the adsorptive hindrance and swallow up interference, be advantageous to be lifted the reliability of correlation analysis test data.

As described above, this case silica dioxide granule filler, its function actually includes being similar to being directed to PDMS materials Inner surface of pipeline carry out chemical modification effect, functioning as its this respect 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 parents The water chemistry decorative layer retention time is short, hydrophilic effect can not keep that situation prolonged enough is different, and particle described in this case is huge Silica dioxide granule filler, its particle being stuck by rheology can not both be moved easily, 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 the skill of surface chemical modification Seen in art effect, its technique effect of this case, be form it is permanent, can not erase, can not consume, not be corroded, not swallowed up , the hydrophilic surface reforming layer being not dissolved, it is just comparable to a kind of in PDMS base materials its relevant surfaces in effect The permanent hydrophilic modifying superficial layer of structure.

It is related that the technical scheme of this case has dissolved its application to dimethyl silicone polymer substrate addressed above totally A series of technical barriers.Based on this case scheme, the very cheap polydimethyl siloxane material of this kind is just possible to micro- at this It is prepared by fluidic chip, production, using etc. field play bigger effect.

Brief description of the drawings

Fig. 1 is the schematic diagram of this case micro fluidic device embodiment chip part construction, it is shown that this structure Depression angle under chip internal pipeline and the structural form of each electrode and each related liquid pool, do not depict in the figure described Micropump and other annexes.

In figure, 1,2,10 be the different liquid pool of three installation positions respectively, and 3 be manifold shape turnout, and 4,7,11,14 are respectively Installation position is different but four laterals parallel with one another for forming UNICOM's structure in parallel, and 5 be its that be installed in lateral 4 The working electrode that specific antibody material in the gold size sensitivity membrane structure of top layer is AIDS specific antibody p24,6 be to be installed in The work that the specific antibody material in its top layer gold size sensitivity membrane structure in lateral 7 is AIDS specific antibody gp41 Make electrode, 12 be that specific antibody material in its top layer gold size sensitivity membrane structure being installed in lateral 11 is AIDS Specific antibody gp120 working electrode, 13 be the spy in its top layer gold size sensitivity membrane structure being installed in lateral 14 Heterogenetic antibody material is AIDS specific antibody gp36 working electrode, and 8 be to electrode, and 9 be reference electrode.

Embodiment

In this case that Fig. 1 is shown embodiment, the structure of the micro fluidic device includes multichannel micro-fluidic chip, should The structure of micro-fluidic chip includes being bonded to each other installing substrate and cover plate together, the substrate and cover plate be plate object or The channel structure via mould pressing process or etching technics formation is contained in tablet, that face towards the cover plate of the substrate, should Substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or simple drilling technology The window structure of formation, be bonded to each other the substrate that is installed together and the cover plate be built into jointly containing pipeline configuration and The micro-fluidic chip for the liquid pool structure being attached thereto, the liquid pool are liquid pool 1, liquid pool 2, liquid pool 10, the locations of structures of the pipeline The interface zone being bonded to each other positioned at the substrate and the cover plate, its side of the window is blocked by the cover plate and opposite side opens, should The locations of structures of window is exactly the liquid pool 1, liquid pool 2, the locations of structures of liquid pool 10, and the quantity of the liquid pool is three, wherein Two liquid pools be sample introduction end that liquid pool 1 and liquid pool 2 its locations of structures are located at the micro-fluidic chip, a remaining liquid pool is liquid Its locations of structures of pond 10 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 is with being somebody's turn to do Sample introduction end is located remotely from each other, and one end of the pipeline is distinguished via the manifold shape turnout 3 for being similarly positioned in the interface zone being bonded to each other With the liquid pool 1 positioned at sample introduction end and the UNICOM of liquid pool 2, the other end of the pipeline and the terminal positioned at the micro-fluidic chip A remaining liquid pool be the UNICOM of liquid pool 10, and, be sequentially respectively installed in the pipeline on diverse location work electricity Pole and to electrode 8 and reference electrode 9, the working electrode is by conductive electrode and is attached on the conductive electrode The gold size sensitive membrane for having embedded AIDS specific antibody is formed, and the construction of the pipeline is in parallel construction, and described is in parallel construction Pipeline be made up of four lateral parallel connections, the quantity of the working electrode is four, the installing position of four working electrodes Put respectively in four laterals, four working electrodes are working electrode 5, working electrode 6, working electrode respectively 12nd, working electrode 13, and, the specific antibody in its top layer gold size sensitivity membrane structure of four working electrodes is to Chinese mugwort respectively Grow four kinds of aids antibody materials that disease antigen can be specifically bound, four kinds of antibody materials be aids antibody p24 respectively with And aids antibody gp41 and aids antibody gp120 and aids antibody gp36, for specifically deploying, 5 be installing The specific antibody material in its top layer gold size sensitivity membrane structure in lateral 4 is AIDS specific antibody p24's Working electrode, 6 be that specific antibody material in its top layer gold size sensitivity membrane structure being installed in lateral 7 is AIDS Specific antibody gp41 working electrode, 12 be special in its top layer gold size sensitivity membrane structure being installed in lateral 11 Property antibody materials be AIDS specific antibody gp120 working electrode, 13 be installed in lateral 14 its top layer gold The working electrode that specific antibody material in glue sensitivity membrane structure is AIDS specific antibody gp36, the working electrode 5, Working electrode 6, working electrode 12, working electrode 13 its material are gold material or thermal decomposition conducting polymer material, the work Make electrode 5, working electrode 6, working electrode 12, its pattern presentation sheet or thread of working electrode 13, and, Micropump, the Micropump It is connected with the sample introduction end of the micro-fluidic chip, the Micropump is the Micropump of external form or the Micropump of built in version, and emphasis is to be somebody's turn to do Its material of substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, the surface of the primary form It is intended to refer to not by any surface chemical modification or the table of the primary form of the material of any surface chemical modification Face；And many silica dioxide granules, many silica dioxide granules are filled in the pipeline, its pipe of the pipeline Chamber is filled up by many silica dioxide granules, its particle size range of the silica dioxide granule between 10 microns with 200 microns it Between, the silica dioxide granule is silica crystalline particles, silica glass granule or silica composition its shared weight Inorganic glass particles of the percentage more than 80%.

Micropump is depicted without in Fig. 1.

Also the associate members such as multiple tracks electrochemical workstation are depicted without in legend.

Each working electrode in this example structure and can be respectively via each special electricity to electrode and reference electrode Cable or say is being got lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as annex or saying interface connection of getting lines crossed.

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 do into or say the embedded micro-fluidic chip The Micropump of the built in version of internal its sample introduction end structure position or the sample introduction end Near-neighbor Structure position, its basic structure key element with it is outer The Micropump for putting form is identical.

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

Involved Micropump can customize to specialized factory.

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

Claims (9)

1. the special cheap AIDS diagnosis micro fluidic device in fluid passage, the structure of the micro fluidic device include multichannel Micro-fluidic chip, the structure of the micro-fluidic chip include being bonded to each other the substrate and cover plate of installing together, the substrate and lid Piece is plate object or tablet, and that face towards the cover plate of the substrate is contained to be formed via mould pressing process or etching technics Channel structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics Or the window structure that simple drilling technology is formed, it is bonded to each other the substrate being installed together and has been built into jointly with the cover plate and contains The micro-fluidic chip of liquid pool structure for having pipeline configuration and being attached thereto, the locations of structures of the pipeline are located at the substrate and the lid The interface zone that piece is bonded to each other, its side of the window is blocked by the cover plate and opposite side opens, and the locations of structures of the window is just It is the locations of structures of the liquid pool, the quantity of the liquid pool is three, and its locations of structures of two liquid pools therein is located at the miniflow The sample introduction end of chip is controlled, its locations of structures of a remaining liquid pool is located at when the actual sample introduction of the micro-fluidic chip is tested in its chip The terminal of liquid flowing, the terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is via being similarly positioned in what this was bonded to each other The manifold shape turnout of interface zone is micro- with being located at this with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline respectively A remaining liquid pool UNICOM for the terminal of fluidic chip, and, sequentially it is respectively installed in diverse location in the pipeline On working electrode and to electrode and reference electrode, the working electrode is by conductive electrode and is attached to the electric conductivity The gold size sensitive membrane for having embedded AIDS specific antibody on electrode is formed, and the construction of the pipeline is in parallel construction, described to be in The pipeline of parallel construction is made up of four lateral parallel connections, and the quantity of the working electrode is four, four working electrodes Installation position respectively in four laterals, and, its top layer gold size sensitivity membrane structure of four working electrodes In specific antibody be the four kinds of aids antibody materials that can be specifically bound to AIDS antigen respectively, four kinds of antibody things Matter is aids antibody p24 and aids antibody gp41 and aids antibody gp120 and aids antibody gp36 respectively, Its material of the working electrode is gold material or thermal decomposition conducting polymer material, and sheet is presented in its pattern of the working electrode Or it is thread, and, Micropump, the Micropump is connected with the sample introduction end of the micro-fluidic chip, the Micropump be external form Micropump or The Micropump of built in version, it is characterised in that its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is primary The surface of 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；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 of the silica dioxide granule For scope 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%.

2. the special cheap AIDS diagnosis micro fluidic device in fluid passage according to claim 1, its feature exist In the pipeline and the lateral and the manifold shape turnout are capillary channel.

3. the special cheap AIDS diagnosis micro fluidic device in fluid passage according to claim 1, its feature exist In the thermal decomposition conducting polymer is the conductive material formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated.

4. the special cheap AIDS diagnosis micro fluidic device in fluid passage according to claim 1, its feature exist In, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the length of the working electrode Between 1 micron to 15000 microns.

5. the special cheap AIDS diagnosis micro fluidic device in fluid passage according to claim 1, its feature exist In the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.

6. the special cheap AIDS diagnosis micro fluidic device in fluid passage according to claim 1, its feature exist In the cover plate its material in structure is dimethyl silicone polymer material.

7. the special cheap AIDS diagnosis micro fluidic device in fluid passage according to claim 1, its feature exist In, positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal this is remaining Air line distance between one liquid pool is between 3 centimetres and 7 centimetres；Described its thickness of cover plate and substrate in structure between Between 1.0 millimeters and 5.0 millimeters.

8. the special cheap AIDS diagnosis micro fluidic device in fluid passage according to claim 1, its feature exist In its particle size range of the silica dioxide granule is between 100 microns and 200 microns.

9. the special cheap AIDS diagnosis micro fluidic device in fluid passage according to claim 1, its feature exist In its inside diameter ranges of the pipeline are between 500 microns and 1000 microns.