CN107670719A

CN107670719A - Four-way and the AIDS diagnosis micro fluidic device of dual drive coupling running

Info

Publication number: CN107670719A
Application number: CN201610688742.7A
Authority: CN
Inventors: 陈航
Original assignee: Individual
Current assignee: Individual
Priority date: 2016-08-02
Filing date: 2016-08-02
Publication date: 2018-02-09

Abstract

The present invention relates to a kind of four-way and the AIDS diagnosis micro fluidic device of dual drive coupling running, belong to analysis testing field.The substrate of AIDS diagnosis micro-fluidic chip is made with dimethyl silicone polymer i.e. PDMS cheap and easily process, a lot of technology barrier be present；This case is directed to the obstacle.This case main points are, the selected PDMS with ecosystem surface of substrate, and the chain ring type magnetic holding device for being equiped with miniature ultrasonic transducer units socket is positioned at the sample liquid stream terminal of the micro-fluidic chip its neighbor positions, interfacial tension is reduced with ultrasonic wave, strong absorbability using PDMS to ultrasonic wave simultaneously, reach ultrasonic intensity rapid decrement in short distance, so as to form interfacial tension difference at the both ends of the chip, the difference provides a kind of strength driven sample liquid stream and flowed along hydrophobic capillary channel to the terminal direction, the strength with Micropump its mechanicalness pumping strength included in structure while intercouple, Collaboration.

Description

Four-way and the AIDS diagnosis micro fluidic device of dual drive coupling running

Technical field

The present invention relates to a kind of four-way and the AIDS diagnosis micro fluidic device of dual drive coupling running, the 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 be etched with the substrate of small fluid course and fit together therewith Cover plate, the small fluid course on the substrate, before upper cover plate is assembled, it is apparent on see to be exactly some micro-channels, to wait until After covering cover plate thereon, just really closure forms the small fluid course, the conduit inner surface of the micro-channel together with The part cover plate that surround the micro-channel forms described small fluid course together；So, it is clear that after assembling completes The small fluid course, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, should The state or property of micro-channel inner surface substantially determine the integrality or property of the small fluid course；Therefore say, this The inner surface state or inner surface property of micro-channel of the individual structure on substrate are key factors；In principle, it is any can The material of its solid forms is kept or kept substantially, can be used to make substrate and cover plate, such as, it can act as substrate and lid The material of piece can be monocrystalline silicon piece, quartz plate, sheet glass, high polymer for example dimethyl silicone polymer, polymethyl methacrylate, Makrolon etc.；Certainly, the selection of substrate and the selection of cover plate be able to can also be differed with identical；From material consumption, make From the point of view of difficulty and application popularization prospect etc. etc., not small difference, the especially choosing of that substrate between these materials be present Material, 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 micro-channel is made on the substrate of sample, and the lower cost for material, base is made with the polydimethyl siloxane material Piece, micro-channel, and the cover plate phase made with the cheap material such as glass or polypropylene or other plastic sheets are being suppressed or etched thereon Coordinate, be a kind of more satisfactory selection seemingly；Certainly, patch material can also select to use cheap dimethyl silicone polymer Material：So, this substrate selection is the scheme of polydimethyl siloxane material, and material is extremely cheap, and making is extremely simple, seems It should be extremely easy to popularize, 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 Strong hydrophobic material, micro-channel is built on this material, if without being operated for the modified of the micro-channel surface, that , after overall assembling is completed, that is, after covering cover plate, because the micro-channel its inner surface in structure occupies most liquid The inner surface of circulation road, then, its strong hydrophobic property of the PDMS micro-channels inner surface, is deciding factor, it can cause Similar to the aqueous solution the fine liquid stream of polar liquid by becoming very difficult, its flow resistance is big, or even in general is micro- Pump is all difficult to promote, certainly, if cover plate also selects to use the PDMS material, then, problem is substantially identical, similar； Therefore, among prior art, modification is modified particular for the micro-channel inner surface on the PDMS material, is necessary behaviour Make；So, this is pretty troublesome for the modified operation of PDMS micro-channel inner surfacesThat falls nor this problem, is formed tight Weight technology puzzlement, be another problem：PDMS polymer molecules inside its body phase of this PDMS material substrate have automatic The characteristic diffuse to the surface, migrated, the spy that this substrate body phase inside PDMS polymer molecules are diffused to the surface, migrated automatically Property, the state after modification by its inner surface of that micro-channel of surface modifying and decorating will be caused can not to maintain long enough Time, the holding time for micro-channel its inner surface state after that is surface-modified be substantially only sufficient to complete laboratory internal The time of test experiments needs；In other words, by surface modification or the PDMS micro-channel inner surfaces of surface modification, it is modified The surface state that is formed can not be lasting afterwards or after saying modification, but soon automatically tends to or say and become surface modification again Surface state before, the strong hydrophobic surface state of that script is returned in the shorter time, then, just think, this The micro-fluidic chip of sample can largely make, mass storage, be widely popularized, and answer is it is obvious that is, impossible.This Micro-channel on PDMS material, if not doing surface modification, similar to the aqueous solution the fine liquid stream of polar solvent can not pump it is logical Cross, chip also cannot just use；And if having done surface modification, its state after modifying can not be persistently kept again, or together Sample can not popularization and application.

So, how to accomplish that substrate can either be made using cheap PDMS material, and the microflute can be released Road inner surface decorating state can not persistently, chip can not largely make, largely lay in and then be widely popularized and such a make ability The puzzlement that the numerous professionals in domain 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 micro-channels inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is person in charge of reception at ceremonies Phenomenon existing for sight.

, 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 micro-channel part, by changing The micro-channel inner surface of modification is learned, its absorption to large biological molecule can be contained, and then avoid large biological molecule Swallowed up by PDMS substrate body phases；But or that old problem, that is, the chemical modification on PDMS material surface is modified Surface state afterwards can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface, move automatically The process of shifting, it soon can become that micro-channel inner surface state being modified by surface chemical modification again script strong and dredge Water 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 micro-channel 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 is enough Reach and contain the absorption process of the PDMS substrate micro-channel inner surfaces to large biological molecule for a long time, and then prevent PDMS substrate body phases The effect of swallowing up to large biological molecule so that related chip manufactured goods be able to maintain that one it is prolonged enough, reasonably guarantee the quality Phase, it is exactly a very intractable problem.The problem equally makes this area numerous as another problem addressed above Professional is entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise. Also be present many year in the problem, so far, also not yet properly settled.

Third, as described above, the PDMS micro-channel inner surfaces are strongly hydrophobic, and targetedly surface chemical modification or surface Chemical modification is difficult to persistently again, therefore, actually can only still belong to effective in the surface state after the modification of its surface or surface modification It is short-term within use it；If having had been subjected to that ofer short duration period of validity, and still by force if use, due to table Again close to hydrophobic state, bigger flowing is then already certainly existed using usual Micropump driving sample liquid stream for surface state Resistance, so, just by increasing Micropump pump power and pumping pressure test liquid can only be forced to flow to target direction flowing, as above Described, this PDMS material is soft, pumps sample liquid stream with too high, mechanical pumping pressure, will cause the substrate Bubbling, expanded, distortion, deformation, also, this high pressure feelings occur for the micro-channel that its sample introduction end includes sample introduction end near zone Under condition, the stripping between substrate and cover plate also easily occurs in the sample introduction end and its micro-channel of near zone and its periphery, Under this situation, the crack for the appearance that sample solution will enter after the stripping between the substrate and cover plate formed and it is horizontal everywhere Stream, this actually results in the damage of the micro-fluidic chip；It is certainly, not in place if surface modification or surface modification script, It can cause said circumstances occur within the of short duration usual term of validity；The feelings of liquid stream driving are being carried out using additional Micropump merely Under condition, the above-mentioned problem exists all the time.As described above, if any surface modification or surface modification etc. were not done completely Pre action, then, the above-mentioned problem will be even more serious, is roused even without micro-channel described in sample introduction end and its near zone occurs The problems such as being peeled off between bubble, expanded, distortion, deformation and substrate and cover plate, merely because the flow resistance is excessive, using high pressure Micropump also may not can drive sample liquid stream to be marched forward towards terminal side.

The content of the invention

The technical problem to be solved by the invention is to provide a package solution, while solve to address above Three aspects a series of problem actually mutually involved together, also, the solution is applied to AIDS Multichannel micro-fluidic chip field is used in diagnosis, forms a kind of new AIDS diagnosis Multichannel device.

The present invention solves the technical problem by following scheme, and the device that the program provides is a kind of four-way and double The AIDS diagnosis micro fluidic device of driving coupling running, the structure of the device include 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, mutually patch are contained in thing, that face towards the cover plate of the substrate Close the substrate being installed together and be built into the micro-fluidic chip containing pipeline configuration, the structure of the pipeline jointly with the cover plate Position is located at the juncture area that the substrate and the cover plate are bonded to each other, the both ends of the pipeline sample introduction with the micro-fluidic chip respectively End and terminal connection, the sample introduction end are the injection ends of the micro-fluidic chip sample solution, and the terminal is micro-fluidic chip reality The terminal that sample solution flows in its chip during the sample introduction test of border, the terminal are located remotely from each other with the sample introduction end, and the terminal is entered with this Between 3 centimetres and 10 centimetres, the terminal links together with terminal liquid pool at the distance between sample end, its knot of the terminal liquid pool The profile of structure is in pond shape, pit shape or cup-shaped, and the terminal liquid pool is used to receive the sample solution for flowing to terminal via the pipeline, Working electrode is sequentially equiped with diverse location in the pipeline and to electrode and reference electrode, the working electrode is by leading Conductive electrodes and the gold size sensitive membrane for having embedded AIDS specific antibody being attached on the conductive electrode are formed, the pipe The construction in road is in parallel construction, and the pipeline in parallel construction is made up of four lateral parallel connections, the working electrode Quantity is four, and the installation position of four working electrodes is located in four laterals respectively, and, this four work Specific antibody in its top layer gold size sensitivity membrane structure of electrode is the four kinds of Chinese mugworts that can be specifically bound to AIDS antigen respectively Disease antibody materials are grown, four kinds of antibody materials are that aids antibody p24 and aids antibody gp41 and AIDS resist respectively Body gp120 and aids antibody gp36, its material of the working electrode be gold material or thermal decomposition conducting polymer material, Sheet or thread is presented in the working electrode its pattern, and emphasis is, its material of the substrate is dimethyl silicone polymer material, the base Its surface of piece is the surface of primary form, the surface of the primary form its be intended to refer to and do not pass through any surface chemical modification Or the surface of the primary form of the material of any surface chemical modification, the structure of the device also include chain ring type magnetic holding device, Six links are shared in its structure of the chain ring type magnetic holding device, the link is in strip, shaft-like or bar-shaped, each adjacent link phase It is mutually be hinged to form chain link, the hexagonal cyclic structure of its appearance profile of the chain link, each drift angle of the hexagonal annular structure its Locations of structures is articulated structure position, and in the link of opposite side position, its material is two therein of the hexagonal annular structure Magnetic conductivity material, its material of the remaining four processes of the hexagonal annular structure is non-magnetic material, the non magnetic material Refer to the material not responded strongly to externally-applied magnetic field, wound in a link among two links of the magnetic conductivity material There is magnet exciting coil, the link for being wound with magnet exciting coil is respectively equiped with a magnetic conduction in the both sides neighbor positions of its magnet exciting coil The pole shoe of property material, shares two pole shoes, and two pole shoes are directed to the link of another magnetic conductivity material, this another Fixed chain for being equiped with miniature ultrasonic transducer units, relying on electromagnetism adhesive strength is attached on its surface of the link of magnetic conductivity material Ring type magnetic holding device is socketed the close position for being positioned at its terminal of the micro-fluidic chip, and, higher-order of oscillation electric signal passes Transmission cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable link together；The chain ring type Magnetic holding device provides a function of facilitating the device to disassemble；Its major function of the miniature ultrasonic transducer units is micro-fluidic During the test of chip actual sample introduction, the ultrasonic wave launched using it reduces sample solution and its inner passage of the micro-fluidic chip Inwall between interfacial tension, can be compatible, also, utilize the sample introduction end and the terminal and the miniature ultrasonic Difference in the distance between wave transducer installation position difference and its ultrasonic intensity experienced, described in induced synthesis Difference between its interfacial tension of sample introduction end and the terminal its interfacial tension, the interface between the micro-fluidic chip both ends Power difference can form pressure gap between the both ends of the micro-fluidic chip, and the pressure gap can drive sample solution to described End flow；The ultrasonic wave that its function of the miniature ultrasonic transducer units also includes being launched with it checks life contained in sample Its absorption on the micro-fluidic chip its inner passage inner surface of thing macromolecular, and then check the dimethyl silicone polymer material Swallow up effect of its body phase of substrate to the large biological molecule；The substrate of the dimethyl silicone polymer material that is soft and having elasticity Its function includes, with its property to the strong absorption of ultrasonic wave, absorbing ultrasonic wave strongly, and thereby in the micro-fluidic core The piece terminal is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end；And Micropump, should Micropump is connected with the sample introduction end；The function of the Micropump is the inwall in the sample solution Yu its inner passage of micro-fluidic chip Between interfacial tension reduced, under the increased precondition of alternate compatibility by the ul-trasonic irradiation, with the machinery of the Micropump Property interfacial tension difference its caused driving force for coming between the both ends of ultrasonic wave induction of pumping strength it is mutual Support, adjust mutually, be mutually coupled, one driving test liquid is pooled in a manner of Collaboration and flows to the terminal direction stream Dynamic strength, some high hydroscopic resin particles are filled with the terminal liquid pool, its opening end of the terminal liquid pool is by breathable microporous film Covered.

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

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

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 its internal sample introduction end structure position or the sample introduction end Near-neighbor Structure position.

The word of magnet exciting coil one art-recognized meanings of itself are known.

The word of magnetic conductivity material one art-recognized meanings of itself are known；The material for belonging to magnetic conductivity material is for example pure Iron, silicon steel, soft magnetic ferrite etc..

Non magnetic material described in this case refers to the material not responded strongly to externally-applied magnetic field, belongs to the non magnetic material The material of matter such as metallic copper, metallic zinc, ormolu, metallic aluminium, almag etc..

The be hinged word art-recognized meanings of itself field in Machine Design is known.

The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and 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 in the microfluidic chip structure includes the lateral, and its internal diameter size may each be any Selected size, still, for using prepare liquid sample less as far as possible and reducing the consideration of reagent loss etc., the pipeline includes The lateral preferably selects the passage of capillary level, and the passage of the capillary level is implied that on its internal diameter and ordinary meaning Capillary the suitable passage of internal diameter.The shape of cross section of its inner passage of capillary can be arbitrary shape, institute State for example circular shape of cross section, oval, square, rectangle, bar shaped, naturally it is also possible to it is the linear of bending arbitrarily be present, Also, the interior shape of the capillary, with the extension of pipeline, the shape of cross section of different parts can also allow to be different Shape.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, 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.

Only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field, It is known.

Various sizes, variously-shaped ultrasonic transducer are commercially available；Its size of commercially available miniature ultrasonic transducer units It may diminish to the magnitude only calculated with millimeter.

Only with regard to miniature ultrasonic transducer units its technique for fixing on general industry application solid body surface its It is known general technology for the professional in ultrasonic technology field for body.This case is not to this expansion superfluous words.

Only with regard to naked PDMS substrates itself micro-channel molding or lithographic technique for, be open-and-shut known skill Art.

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 device can also include higher-order of oscillation electric signal generator；The higher-order of oscillation electric signal transmission cable Its other end can be connected with the higher-order of oscillation electric signal generator.

The involved higher-order of oscillation electric signal generator technology of itself, come for the professional in ultrasonic technology field Say, be simple and known；The higher-order of oscillation electric signal generator can customize to ultrasonic instrument specialized factory.

The preferred scope of its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 5 milliwatts and 9000 milliwatts Between；The preferred scope of the frequency of its ultrasonic wave operationally launched of the miniature ultrasonic transducer units be between 100KHz with Between 12MHz.

Only for the word of high hydroscopic resin one art-recognized meanings of itself, come for the professional of chemical field Say, be known.

The high hydroscopic resin is commercially available.

Only for the word of breathable microporous film one art-recognized meanings of itself, for the professional of technical field of membrane, It is known.

The breathable microporous film is commercially available.

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

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

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

The cover plate in chip structure, its material can allow to be any electrical insulating property material, such as：Polypropylene, Glass, polymethyl methacrylate, dimethyl silicone polymer, etc., in order to make smaller size of micro-fluidic chip, for example do Into the micro-fluidic chip of only 2.0 centimetres to 3.0 centimetres of super-small of length, and realized in the extremely short distance to ultrasonic wave Extremely fast decay, can preferably dimethyl silicone polymer be used as cover plate.Certainly, selected on large-sized micro-fluidic chip Using dimethyl silicone polymer it is used as the cover plate, and this case technical scheme is allowed.

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 drives liquid stream in the capillary channel of the four-way micro-fluidic chip with dual drive coupling operating mode Middle flowing, four kinds of AIDS diagnosis antigens are detected respectively using four-way electrochemical analytical instrument.

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 AIDS The AIDS for the corresponding horseradish peroxidase-labeled that antigen molecule is embedded by gold size sensitive membrane on electrode surface in each passage Specific antibody captures.

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.

It is an advantage of the invention that its close position relies on electromagnetism adhesive strength set in the terminal of the micro-fluidic chip The described chain ring type magnetic holding device of positioning is connect, is installed with institute's attaching in the chain ring type magnetic holding device one magnetic conductivity link micro- Type ultrasonic transducer, the low-power launched using it, the ultrasonic wave of high-frequency band so that without surface chemical modification or It is compatible between strong hydrophobic its tube wall of micro-fluidic chip internal pipeline and the test object aqueous solution of surface chemical modification Property be significantly increased, this is sample liquid stream by providing a realistic possibility；Meanwhile utilize dimethyl silicone polymer substrate Its strong absorbability to ultrasonic wave, in shorter distance, it is, from the terminal to the sample introduction end In the very short distance of only several centimeters yardsticks, reach the rapid decrement of ultrasonic intensity, thereby described in the micro-fluidic chip The difference of the interfacial tension is caused at both ends, and the difference of the interfacial tension between the both ends can cause a kind of driving force, this kind Its function of driving force is to drive sample liquid stream in strong hydrophobic capillary channel originally caused by interfacial tension difference The introversive terminal direction flowing；And the simultaneous Micropump in structure, its function are, in the sample solution and the miniflow Interfacial tension between the inwall of its inner passage of control chip is reduced, the increased premise of alternate compatibility by the ul-trasonic irradiation Under the conditions of, the interfacial tension difference come between the both ends of ultrasonic wave induction with the mechanicalness of Micropump pumping strength its Caused driving force is supported mutually, adjusts mutually, is mutually coupled, and one driving sample is pooled in a manner of Collaboration The strength that liquid stream flows to the terminal direction；The presence of the Micropump so that the miniature ultrasonic transducer units its ultrasonic wave transmitting Intensity can be allowed to appropriate reduction, and this is particularly suitable for for the situation containing ultrasonic wave sensitive composition in detection object；And by In the presence of the ultrasonic transducer and its radiated ultrasonic wave, it is possible to increase alternate compatibility, reduce interfacial tension, and provide The both ends interfacial tension difference special driving force caused by it, then, in this case, sample liquid stream its in the microflute Flow resistance in road is greatly reduced, and correspondingly, its running resistance of the Micropump is greatly reduced, so, the Micropump just can with than Relatively low pumping pressure carries out the pumping work for the sample solution, because mechanical pumping pressure is greatly reduced, Therefore, in such a situation, be just not susceptible to caused by sample introduction terminal tool pumping pressure is excessive the sample introduction end and Peel off etc. and to ask between the micro-channel bubbling of its near zone, expansion, deformation, distortion and the region substrate and cover plate Topic；This case dual drive couples the scheme of running and adds handling, the Neng Gouyun for sample fluid flow action Perhaps pressure etc. multiple indexs are pumped to be directed to the flowing using ultrasonic intensity, ultrasonic frequency, Micropump pump power, Micropump Flow rate, flowing action include flow forward or pause flowing or accelerate flowing etc. flowing action progress multi-parameter it is accurate Manipulation；By the scheme of this case dual drive coupling running, entirely without must its be micro- to the substrate of the dimethyl silicone polymer material Conduit etc. relevant surfaces carry out any surface chemical modification or surface chemical modification, have altogether dispensed with the surface chemical modification Or the laborious procedures of surface chemical modification；On the other hand, the ultrasonic wave of the low-power, high-frequency band, additionally it is possible to contain in sample Absorption of the large biological molecule on literalness naked its inner surface of pipeline of dimethyl silicone polymer substrate, and then contain should Swallow up effect of its body phase of dimethyl silicone polymer substrate to the large biological molecule；The antigen, antibody and antigen are with resisting The Reversible binding thing of body is all the type for belonging to described large biological molecule certainly；Due to described suction-operated and described The effect of swallowing up effectively is contained that therefore, dependence test result will be better able to objectively reflect actual conditions；The low-power, The effect of high-frequency band ultrasonic wave, also include facilitating what the Reversible binding between antigen, antibody react quickly to reach certainly, this makes Obtaining dependence test operation can be with than the completion of faster speed.

As described above, the presence of the Micropump so that its ultrasonic wave emissive porwer of the miniature ultrasonic transducer units can be permitted Perhaps appropriateness reduces, then, the feature helps to protect its sensitive coating of the working electrode, is allowed to from ultrasound injury.

Based on this case scheme, completely without carrying out coming to the surface for its relevant surfaces of dimethyl silicone polymer substrate Modification or surface chemical modification operation are learned, therefore, this surface chemical modification layer or surface chemical modification layer not need In the presence of, then, its body phase interior polymer molecule of the dimethyl silicone polymer substrate constantly diffuses to the surface, migrates its institute automatically It is caused that the damaging influence of the surface chemical modification layer or surface chemical modification layer is also just not present.

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, this kind be very cheap and the easily dimethyl silicone polymer material of processing and fabricating Material be just possible in the micro-fluidic chip its prepare, production, using etc. field play bigger effect.

Attached in the chain ring type magnetic holding device one magnetic conductivity link in this case structure it is fixed installed it is described miniature Ultrasonic transducer, this architecture provides a function of facilitating the device to disassemble, in this way, the chain ring type magnetic holding device is together with it The miniature ultrasonic transducer units attached in one magnetic conductivity link just easily can be mutually disengaged with the micro-fluidic chip, So, the component that the part can freely depart from is reused many times in which just can circulate benignly；The architectural feature is advantageous to save The about use cost of the device.

Brief description of the drawings

Fig. 1 be this case device chain ring type magnetic holding device its with appearance side rough under the micro-fluidic chip socket state View, the legend and indicates the relative position relation under the socket state between each component.

Fig. 2 is the outside side view under another viewing angle of this case device；Fig. 2 viewing angle and Fig. 1's Viewing angle is mutually perpendicular to；The components such as infusion tube and Micropump are depicted without in Fig. 2.

In figure, 1 is chain ring type magnetic holding device, and 2 be the terminal of the micro-fluidic chip, and 3 be the institute of the micro-fluidic chip Sample introduction end is stated, 4 be the substrate of dimethyl silicone polymer material, and 5 be cover plate, and 6 be miniature ultrasonic transducer units, and 7 be the higher-order of oscillation Electric signal transmission cable, 8,15 respectively be positioned at different structure position two magnetic conductivity materials link, two magnetic conductivity The link of material end-to-end relation each other in the structure shown here, 9,22 be two pole shoes positioned at different structure position respectively, 10,12, 14th, 17,19,21 be six pin joints in six diverse locations respectively, and 11,13,18,20 be to be in four different positions respectively The link for the four non magnetic materials put, 16 be magnet exciting coil, and 23 be infusion tube, and 24 be Micropump；The chain ring type in legend Magnetic holding device structure is only the legend structure of signal, and the actual chain ring type magnetic holding device structure is not limited to the legend chain ring type electromagnetism Clamp structure；Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, its try The flow direction of sample liquid stream.

Embodiment

In this case that Fig. 1 and Fig. 2 are shown embodiment, the structure of the device includes multichannel micro-fluidic chip, should The structure of micro-fluidic chip includes being bonded to each other the substrate 4 and cover plate 5 of installing together, and the substrate 4 and cover plate 5 are tabular The conduit knot via mould pressing process or etching technics formation is contained in thing or tablet, that face towards the cover plate 5 of the substrate 4 Structure, it is bonded to each other the substrate 4 being installed together and has been built into the micro-fluidic chip containing pipeline configuration jointly with the cover plate 5, The locations of structures of the pipeline is located at the juncture area that the substrate 4 is bonded to each other with the cover plate 5, and the both ends of the pipeline are micro- with this respectively The sample introduction end 3 of fluidic chip and terminal 2 connect, and the sample introduction end 3 is the injection end of the micro-fluidic chip sample solution, the terminal 2 be the terminal of sample solution flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, the terminal 2 and the phase of sample introduction end 3 Mutually remote, between 3 centimetres and 10 centimetres, the terminal 2 joins with terminal liquid pool for the distance between the terminal 2 and the sample introduction end 3 It is tied, the profile of its structure of the terminal liquid pool is in pond shape, pit shape or cup-shaped, and the terminal liquid pool is used to receive via the pipe Road flow to the sample solution of terminal 2, working electrode is sequentially equiped with diverse location in the pipeline and to electrode and Reference electrode, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded AIDS disease-specific The gold size sensitive membrane of antibody is formed, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by four branched pipes Road is in parallel to be formed, and the quantity of the working electrode is four, and the installation position of four working electrodes is located at described four respectively In lateral, and, the specific antibody in its top layer gold size sensitivity membrane structure of four working electrodes is to AIDS respectively Four kinds of aids antibody materials that sick antigen can be specifically bound, four kinds of antibody materials be respectively aids antibody p24 and Aids antibody gp41 and aids antibody gp120 and aids antibody gp36, its material of the working electrode is gold Sheet or thread is presented in material or thermal decomposition conducting polymer material, the working electrode its pattern, and emphasis is, the substrate 4 its Material is dimethyl silicone polymer material, and its surface of substrate 4 is the surface of primary form, its meaning of the surface of the primary form Refer to not by any surface chemical modification or the surface of the primary form of the material of any surface chemical modification, the dress The structure put also includes chain ring type magnetic holding device 1, shared in its structure of the chain ring type magnetic holding device 1 six links 8,11,13, 15th, 18,20, in strip, shaft-like or bar-shaped, each adjacent link is hinged to form chain the link 8,11,13,15,18,20 Ring, the hexagonal cyclic structure of its appearance profile of the chain link, each drift angle 10 of the hexagonal annular structure, 12,14,17,1g, 21 its locations of structures are articulated structure position, two therein links 8,15 for being in opposite side position of the hexagonal annular structure Its material is magnetic conductivity material, and its material of the remaining four processes 11,13,18,20 of the hexagonal annular structure is non magnetic Material, the non magnetic material refer to the material not responded strongly to externally-applied magnetic field, two links of the magnetic conductivity material Among a link 15 on be wound with magnet exciting coil 16, this is wound with the link 15 of magnet exciting coil 16 in its magnet exciting coil 16 The pole shoe of a magnetic conductivity material is respectively equiped with the neighbor positions of both sides, shares two pole shoes 9,22, two pole shoes 9, 22 are directed to the link 8 of another magnetic conductivity material, and fixed installing is attached on its surface of the link 8 of another magnetic conductivity material There are miniature ultrasonic transducer units 6, rely on the chain ring type magnetic holding device 1 socket of electromagnetism adhesive strength to be positioned at the micro-fluidic chip The close position of its terminal 2, and, higher-order of oscillation electric signal transmission cable 7, the higher-order of oscillation electric signal transmission cable 7 One end linked together with the miniature ultrasonic transducer units 6；The chain ring type magnetic holding device 1 provides one and facilitates the device to tear open The function of solution；Its major function of the miniature ultrasonic transducer units 6 is in the actual sample introduction test of micro-fluidic chip, is sent out using it The ultrasonic wave penetrated reduces the interfacial tension between sample solution and the inwall of its inner passage of micro-fluidic chip, can It is compatible, also, utilize the sample introduction end 3 and the distance between the terminal 2 and the installation position of miniature ultrasonic transducer units 6 Difference in difference and its ultrasonic intensity experienced, its interfacial tension of sample introduction end 3 described in induced synthesis and the end The difference between 2 its interfacial tension is held, the interfacial tension difference between the micro-fluidic chip both ends 2,3 can be in the micro-fluidic core Pressure gap is formed between the both ends 2,3 of piece, the pressure gap can drive sample solution to be flowed to the direction of terminal 2；Should The ultrasonic wave that miniature ultrasonic transducer units 6 its functions also includes being launched with it check large biological molecule contained in sample its Absorption on the micro-fluidic chip its inner passage inner surface, so check the dimethyl silicone polymer material substrate 4 its Swallow up effect of the body phase to the large biological molecule；It is soft and have the substrate 4 of the dimethyl silicone polymer material of elasticity its function Including with its property to the strong absorption of ultrasonic wave, being absorbed strongly to ultrasonic wave, and thereby at the micro-fluidic chip end End 2 is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 3；And Micropump 24, this is micro- Pump 24 is connected with the sample introduction end 3；The function of the Micropump 24 is, in the sample solution and its inner passage of the micro-fluidic chip Interfacial tension between wall is reduced, under the increased precondition of alternate compatibility by the ul-trasonic irradiation, with the Micropump 24 Interfacial tension difference its caused driving force that mechanicalness pumping strength is come between the both ends 2,3 of ultrasonic wave induction Amount is supported mutually, adjusts mutually, is mutually coupled, and one driving test liquid is pooled in a manner of Collaboration and flows to the terminal The strength of 2 directions flowing, is filled with some high hydroscopic resin particles in the terminal liquid pool, and its opening end of the terminal liquid pool is breathed freely Microporous barrier is covered.

Arrow in legend indicate the micro-fluidic chip its in actual motion, by both ends 2,3 pressure differentials drive, its The flow direction of sample liquid stream.

The associate members such as the higher-order of oscillation electric signal generator are depicted without in Fig. 1 and Fig. 2.

Involved magnetic conductive material and involved nonmagnetic substance market are on sale.

Involved miniature ultrasonic transducer units 6 are commercially available；It can also be customized to ultrasonic transducer producer.

The Micropump 24 can customize to specialized factory.

Involved higher-order of oscillation electric signal transmission cable 7 is commercially available；Can also be special to ultrasonic transducer producer or cable Industry producer customizes.

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

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 do into or say the embedded micro-fluidic chip The Micropump of the built in version of its internal sample introduction end structure position or the sample introduction end Near-neighbor Structure position.Micropump in legend is external The Micropump of form；The Micropump can certainly do into or say sample introduction end or its neighbour knot inside the embedded microfluidic chip structure The Micropump of the built in version of structure position, its basic structure key element are identical with the Micropump of external form.

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

Claims

1. the AIDS diagnosis micro fluidic device that four-way and dual drive coupling operate, the structure of the 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, be bonded to each other the substrate being installed together and be built into jointly containing the micro-fluidic of pipeline configuration with the cover plate Chip, the locations of structures of the pipeline are located at the juncture area that the substrate is bonded to each other with the cover plate, the both ends of the pipeline respectively with The sample introduction end of the micro-fluidic chip and terminal connection, the sample introduction end is the injection end of the micro-fluidic chip sample solution, the end End is the terminal of sample solution flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, and the terminal and the sample introduction end are mutual Remote, between 3 centimetres and 10 centimetres, the terminal is contacted one with terminal liquid pool for the distance between the terminal and the sample introduction end Rise, the profile of its structure of the terminal liquid pool be in pond shape, pit shape or cup-shaped, and the terminal liquid pool is used to receive via pipeline flowing To the sample solution of terminal, working electrode is sequentially equiped with diverse location in the pipeline and to electrode and reference electricity Pole, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded AIDS specific antibody Gold size sensitive membrane is formed, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by four lateral parallel connections Form, the quantity of the working electrode is four, and the installation position of four working electrodes is located at four branched pipes respectively In road, and, the specific antibody in its top layer gold size sensitivity membrane structure of four working electrodes is to AIDS antigen respectively The four kinds of aids antibody materials that can be specifically bound, four kinds of antibody materials are aids antibody p24 and AIDS respectively Antibody gp41 and aids antibody gp120 and aids antibody gp36, its material of the working electrode be gold material or Conducting polymer material is thermally decomposed, sheet or thread is presented in its pattern of the working electrode, it is characterised in that its material of the substrate Dimethyl silicone polymer material, its surface of the substrate is the surface of primary form, the surface of the primary form its be meant to It is the surface of the primary form for the material for not passing through any surface chemical modification or any surface chemical modification, the device Structure also includes chain ring type magnetic holding device, shares six links in its structure of the chain ring type magnetic holding device, the link is in bar Shape, shaft-like or bar-shaped, each adjacent link is hinged to form chain link, the hexagonal cyclic structure of its appearance profile of the chain link, should Its locations of structures of each drift angle of hexagonal annular structure is articulated structure position, two therein of the hexagonal annular structure Its material of link in opposite side position is magnetic conductivity material, and its material of the remaining four processes of the hexagonal annular structure is Non magnetic material, the non magnetic material refer to the material not responded strongly to externally-applied magnetic field, the two of the magnetic conductivity material Magnet exciting coil is wound with a link among individual link, this is wound with both sides of the link in its magnet exciting coil of magnet exciting coil The pole shoe of a magnetic conductivity material is respectively equiped with neighbor positions, shares two pole shoes, two pole shoes are directed to another The link of individual magnetic conductivity material, attach on its surface of the link of another magnetic conductivity material and fixed be equiped with miniature ultrasonic and change Can device, rely on the chain ring type magnetic holding device socket of electromagnetism adhesive strength to be positioned at the neighbouring of the micro-fluidic chip its terminal Position, and, higher-order of oscillation electric signal transmission cable, one end and the miniature ultrasonic of the higher-order of oscillation electric signal transmission cable Transducer links together；The chain ring type magnetic holding device provides a function of facilitating the device to disassemble；The miniature ultrasonic Its major function of transducer is that the ultrasonic wave launched using it is molten to reduce sample in the actual sample introduction test of micro-fluidic chip Interfacial tension between liquid and the inwall of its inner passage of micro-fluidic chip, can be compatible, also, utilizes the sample introduction End and the distance between the terminal and the miniature ultrasonic transducer units installation position difference and its ultrasound experienced Difference between difference in intensity of wave, its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension, should Interfacial tension difference between the micro-fluidic chip both ends can form pressure gap between the both ends of the micro-fluidic chip, should Pressure gap can drive sample solution to the end flow；Its function of the miniature ultrasonic transducer units also includes being launched with it Ultrasonic wave check in sample contained large biological molecule its absorption on the micro-fluidic chip its inner passage inner surface, And then check swallow up effect of its body phase of the substrate of the dimethyl silicone polymer material to the large biological molecule；Softness simultaneously has elasticity The substrate of the dimethyl silicone polymer material its function include, with its property to the strong absorption of ultrasonic wave, carrying out ultrasonic wave It is strong to absorb, and thereby realize ultrasonic wave within micro-fluidic chip terminal to the limited short distance between the sample introduction end The rapid decrement of intensity；And Micropump, the Micropump are connected with the sample introduction end；The function of the Micropump is, in the sample solution with being somebody's turn to do Interfacial tension between the inwall of its inner passage of micro-fluidic chip is reduced by the ul-trasonic irradiation, alternate compatibility is increased It is poor with the interfacial tension that the mechanicalness pumping strength of the Micropump is come between the both ends of ultrasonic wave induction under precondition Its different caused driving force is supported mutually, adjusts mutually, is mutually coupled, and one driving is pooled in a manner of Collaboration Test liquid flows to the strength of the terminal direction flowing, and some high hydroscopic resin particles, the terminal are filled with the terminal liquid pool Its opening end of liquid pool is covered by breathable microporous film.

2. four-way according to claim 1 and the AIDS diagnosis micro fluidic device of dual drive coupling running, its It is characterised by, it is capillary channel that the pipeline, which includes the lateral,.

3. four-way according to claim 1 and the AIDS diagnosis micro fluidic device of dual drive coupling running, its It is characterised by, the thermal decomposition conducting polymer is the electric conductivity formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated Material.

4. four-way according to claim 1 and the AIDS diagnosis micro fluidic device of dual drive coupling running, its Be characterised by, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the working electrode Length between 1 micron to 15000 microns.

5. four-way according to claim 1 and the AIDS diagnosis micro fluidic device of dual drive coupling running, its It is characterised by, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.

6. four-way according to claim 1 and the AIDS diagnosis micro fluidic device of dual drive coupling running, its It is characterised by, the cover plate its material in structure is dimethyl silicone polymer material.

7. four-way according to claim 1 and the AIDS diagnosis micro fluidic device of dual drive coupling running, its It is characterised by, the Micropump is miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.

8. four-way according to claim 1 and the AIDS diagnosis micro fluidic device of dual drive coupling running, its It is characterised by, described its thickness of cover plate and substrate in structure is between 1.0 millimeters and 5.0 millimeters.

9. four-way according to claim 1 and the AIDS diagnosis micro fluidic device of dual drive coupling running, its Be characterised by, the structure of the device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission cable its The other end is connected with the higher-order of oscillation electric signal generator.

10. four-way according to claim 1 and the AIDS diagnosis micro fluidic device of dual drive coupling running, its It is characterised by, for its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units between 5 milliwatts and 9000 milliwatts, this is miniature The frequency of its ultrasonic wave operationally launched of ultrasonic transducer is between 100KHz and 12MHz.