CN107670716A

CN107670716A - A kind of AIDS diagnosis for being related to hydrophobic substrate multichannel micro-fluidic chip device

Info

Publication number: CN107670716A
Application number: CN201610688603.4A
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 AIDS diagnosis for being related to hydrophobic substrate multichannel micro-fluidic chip device, 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, some technology barriers be present；This case is directed to the obstacle.This case main points are, the selected PDMS with ecosystem surface of substrate, and fastening is positioned at the sample liquid stream terminal of the micro-fluidic chip its neighbor positions manually by the hinge-type fixture for being attached to miniature ultrasonic transducer units, 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

A kind of AIDS diagnosis for being related to hydrophobic substrate multichannel micro-fluidic chip device

Technical field

The present invention relates to a kind of AIDS diagnosis for being related to hydrophobic substrate multichannel micro-fluidic chip device, belong to analysis Testing field.

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 for miniflow Past of control technology, now, and, vision of the future etc. etc., suffer from detail, be deep into long opinion of detail State.

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 that one kind is related to hydrophobic substrate AIDS diagnosis multichannel micro-fluidic chip device, the structure of the device includes multichannel micro-fluidic chip, and this is micro-fluidic The structure of 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 antigen 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 antigen 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 antibody respectively Disease antigenic substance is grown, four kinds of antigenic substances are AIDS specific antigen p24, gp41, gp120 and gp36 respectively, the work Making electrode, its material is gold material or thermally decomposes conducting polymer material, and sheet or silk is presented in its pattern of the working electrode Shape, emphasis be, its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, the original The surface of raw form its be intended to refer to not by any surface chemical modification or the material of any surface chemical modification The surface of primary form, the structure of the device also include hinge-type fixture, hinge-type fixture its appearance profile likeness in form hinge, should Hinge-type fixture is by two hinges being mutually hinged and through a fastening screw of two hinges and one The nut of fastening and hand break loose manually that is used for for matching with the fastening screw and being connected together with the fastening screw is formed, should Two hinges of hinge-type fixture are respectively mutually drawn close with its tip and clamp the micro-fluidic chip, and the tip is positioned at the miniflow Control chip the neighbouring terminal locations of structures on, in a hinge at least in attach fixation be equiped with it is miniature Ultrasonic transducer, and, higher-order of oscillation electric signal transmission cable, one end of the higher-order of oscillation electric signal transmission cable is micro- with this Type ultrasonic transducer links together；The hinge-type fixture provides a function of facilitating the device to disassemble；This is miniature super Its major function of acoustic wave transducer is that the ultrasonic wave launched using it is tried to reduce in the actual sample introduction test of micro-fluidic chip Interfacial tension between sample solution and the inwall of its inner passage of micro-fluidic chip, can be compatible, also, described in utilization Sample introduction end and the distance between the terminal and the miniature ultrasonic transducer units installation position difference and its experienced Difference between difference on ultrasonic intensity, its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension Different, the interfacial tension difference between the micro-fluidic chip both ends can form pressure differential between the both ends of the micro-fluidic chip Different, the pressure gap can drive sample solution to the end flow；Its function of the miniature ultrasonic transducer units also includes with it The ultrasonic wave launched check in sample contained large biological molecule its on the micro-fluidic chip its inner passage inner surface Absorption, and then check swallow up effect of its body phase of the substrate of the dimethyl silicone polymer material to the large biological molecule；It is soft And the substrate of the dimethyl silicone polymer material its function of having elasticity is included with its property to the strong absorption of ultrasonic wave, to super Sound wave is absorbed strongly, and thereby real within micro-fluidic chip terminal to the limited short distance between the sample introduction end The rapid decrement of existing ultrasonic intensity；And Micropump, the Micropump are connected with the sample introduction end；The function of the Micropump is, in the sample Interfacial tension between solution and the inwall of its inner passage of micro-fluidic chip is reduced, alternate compatible by the ul-trasonic irradiation Property increased precondition under, the boundary that is come with the mechanicalness of Micropump pumping strength between the both ends of ultrasonic wave induction Tension difference its caused driving force in face is supported mutually, adjusts mutually, is mutually coupled, and is pooled in a manner of Collaboration One driving test liquid flows to the strength of the terminal direction flowing, and some high hydroscopic resins are filled with the terminal liquid pool Grain, its opening end of the terminal liquid pool are covered by breathable microporous film.

Described miniature ultrasonic transducer units can certainly be all installed in two hinges；But only install one Individual miniature ultrasonic transducer units are dealt with enough to be used.

The word of hinge one art-recognized meanings of itself are known.

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 or miniature air driven pump.

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 gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and AIDS specific antigen 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 Specific Antigen is the AIDS antigen 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 antigen 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 antibodies are detected respectively using four-way electrochemical analytical instrument.

Corresponding four kinds of aids antibodies are detected with four kinds of AIDS antigens, with detecting phase with four kinds of aids antibodies The four kinds of AIDS antigens answered, similarly, can diagnosis of aids；The principle of its foundation is, must in AIDS patient It is so antigen, antibody and deposits, and mutual Reversible binding, form reversible conjugate, therefore, antibody and thereby is detected with antigen Diagnosis of aids, with being gone to detect antigen and diagnosis of aids with antibody, diagnostic purpose can be reached.Certainly, different means Its corresponding electrode sensitive decorative layer technically and differs.

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 antibody molecule is embedded by gold size sensitive membrane on electrode surface in each passage Specific antigen captures.

2nd, the AIDS specific antigen of horseradish peroxidase-labeled is formed with the aids antibody 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 antibody.

It is an advantage of the invention that its close position positions the hinge-type folder in the terminal of the micro-fluidic chip Tool, the miniature ultrasonic transducer units installed with institute's attaching in the hinge-type fixture its hinge, the low-power launched using it, height The ultrasonic wave of frequent section so that without in strong hydrophobic micro-fluidic chip of surface chemical modification or surface chemical modification Compatibility between its tube wall of portion's pipeline and the test object aqueous solution is significantly increased, and this is sample liquid stream by providing one Realistic possibility；Meanwhile using its strong absorbability to ultrasonic wave of dimethyl silicone polymer substrate, in shorter distance It is interior, it is, in from the terminal to the very short distance of only several centimeters yardsticks the sample introduction end, it is strong to reach ultrasonic wave The rapid decrement of degree, thereby causes the difference of the interfacial tension at the both ends of the micro-fluidic chip, between the both ends The difference of interfacial tension can cause a kind of driving force, and this kind its function of driving force caused by interfacial tension difference is to drive Sample liquid stream is caught up with to be flowed originally in strong hydrophobic capillary channel to the terminal direction；And simultaneous institute in structure Micropump is stated, its function is that the interfacial tension between the inwall of the sample solution and its inner passage of micro-fluidic chip is by this Ul-trasonic irradiation and reduce, under the increased precondition of alternate compatibility, come with the mechanicalness of Micropump pumping strength super with this Interfacial tension difference its caused driving force between the both ends of sound wave induction supports mutually, adjustment, mutually mutually Coupling, the strength that one driving test liquid flows to the terminal direction flowing is pooled in a manner of Collaboration；The Micropump In the presence of so that its ultrasonic wave emissive porwer of the miniature ultrasonic transducer units can be allowed to appropriate reduction, and this is for detection object In the situation containing ultrasonic wave sensitive composition be particularly suitable for；And depositing by the ultrasonic transducer and its radiated ultrasonic wave , it is possible to increase alternate compatibility, interfacial tension is reduced, and provide the both ends interfacial tension difference its caused special drive Amount of power, then, in this case, its flow resistance in the micro-channel of sample liquid stream is greatly reduced, correspondingly, the Micropump Its running resistance is greatly reduced, and so, the Micropump just can be to carry out being directed to the sample solution than relatively low pumping pressure Pumping work, because mechanical pumping pressure is greatly reduced, therefore, in such a situation, be just not susceptible to because entering The micro-channel bubbling of the sample introduction end and its near zone caused by sample terminal tool pumping pressure is excessive, expansion, deformation, Between distortion and the region substrate and cover plate the problems such as stripping etc.；This case dual drive couples the scheme of running and added For the handling of sample fluid flow action, can allow for using ultrasonic intensity, ultrasonic frequency, Micropump pumping work( Rate, Micropump pumping pressure etc. multiple indexs are to be directed to the flow rate of the flowing, flowing action includes flow forward or pause Flowing accelerates flowing etc. flowing action progress multi-parameter accurately to manipulate；The scheme operated by this case dual drive coupling, Repaiied entirely without any surface chemistry must be carried out to the substrate of the dimethyl silicone polymer material its micro-channel etc. relevant surfaces Decorations or surface chemical modification, have altogether dispensed with the laborious procedures of the surface chemical modification or surface chemical modification；On the other hand, should The ultrasonic wave of low-power, high-frequency band, additionally it is possible to contain the large biological molecule in sample in the literalness naked poly dimethyl Absorption on its inner surface of pipeline of siloxanes substrate, and then contain that its body phase of dimethyl silicone polymer substrate is big to the biology The effect of swallowing up of molecule；The Reversible binding thing of the antigen, antibody and antigen and antibody is all to belong to described biology certainly The type of macromolecular；Because described suction-operated and the described effect of swallowing up effectively are contained, therefore, dependence test knot Fruit will be better able to objectively reflect actual conditions；The effect of the low-power, high-frequency band ultrasonic wave, it is certainly also anti-including facilitating The quick of Reversible binding reaction between former, antibody is reached, and this causes 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.

The miniature ultrasonic transducer units have been installed in fixation in the hinge-type fixture its hinge in this case structure, the structure A function of facilitating the device to disassemble is provided, in this way, the hinge-type fixture is together with miniature ultrasonic appended in its hinge Transducer just easily can be mutually disengaged with the micro-fluidic chip, then, the component that the part can freely depart from just can be good Property is re-used cyclically many times；The architectural feature is advantageous to save the use cost of the device.

Brief description of the drawings

Fig. 1 is its rough outside side view of this case micro flow control chip device.

In figure, 1 is hinge-type fixture, and 2 sign linkwork positions, 3 be fastening screw, and 4 be higher-order of oscillation telecommunication Number transmission cable, 5 be miniature ultrasonic transducer units, and 6,11 be two different hinges of locations of structures respectively, and 7 be cover plate, and 8 be base Piece, 9 be sample introduction end, and 10 be terminal, and 12 be nut, and 13 be infusion tube, and 14 be Micropump；The hinge-type clamp structure in legend Only it is the legend structure of signal, actual its structure of the hinge-type fixture is not limited to the legend hinge-type clamp structure；In legend Arrow indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, the flow direction of its sample liquid stream.

Embodiment

In this case that Fig. 1 is shown embodiment, the structure of the device includes multichannel micro-fluidic chip, and this is micro-fluidic The structure of chip includes being bonded to each other the substrate 8 and cover plate 7 of installing together, and the substrate 8 and cover plate 7 are plate object or piece The channel structure via mould pressing process or etching technics formation, phase are contained in shape thing, that face towards the cover plate 7 of the substrate 8 The substrate 8 being mutually jointly mounted to together has been built into the micro-fluidic chip containing pipeline configuration jointly with the cover plate 7, the pipeline Locations of structures be located at the juncture area that the substrate 8 and the cover plate 7 are bonded to each other, the both ends of the pipeline respectively with the micro-fluidic core The sample introduction end 9 of piece and terminal 10 connect, and the sample introduction end 9 is the injection end of the micro-fluidic chip sample solution, and the terminal 10 is The terminal that sample solution flows in its chip when the actual sample introduction of the micro-fluidic chip is tested, the terminal 10 and the sample introduction end 9 are mutual Remote, between 3 centimetres and 10 centimetres, the terminal 10 joins with terminal liquid pool for the distance between the terminal 10 and the sample introduction end 9 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 10, 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 antigen 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 antigen in its top layer gold size sensitivity membrane structure of four working electrodes is to AIDS respectively Four kinds of AIDS antigenic substances that sick antibody can be specifically bound, four kinds of antigenic substances are AIDS specific antigen respectively P24, gp41, gp120 and gp36, its material of the working electrode is gold material or thermally decomposes conducting polymer material, described Sheet or thread is presented in working electrode its pattern, and emphasis is, its material of the substrate 8 is dimethyl silicone polymer material, the substrate 8 Its surface is the surface of primary form, the surface of the primary form its be intended to refer to not by 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 hinge-type fixture 1, the hinge Formula fixture 1 its appearance profile likeness in form hinge, the hinge-type fixture 1 is by two hinges 6,11 for being mutually hinged and runs through One fastening screw 3 of two hinges 6,11 and one match with the fastening screw 3 and are socketed in one with the fastening screw 3 Rise be used to fasten manually and the nut 12 of hand break loose is formed, the nut 12 employ in this example be easier it is manually operated Butterfly nut, butterfly nut is commercially available, and two hinges 6,11 of the hinge-type fixture 1 are respectively mutually drawn close and pressed from both sides with its tip The micro-fluidic chip is held, the tip is positioned in the locations of structures of the neighbouring terminal 10 of the micro-fluidic chip, at least existed Attach to fix in one of those described hinge and be equiped with miniature ultrasonic transducer units, in this example, the miniature ultrasonic transducer units 5 It is to attach to be fixed in hinge 6, and, higher-order of oscillation electric signal transmission cable 4, the higher-order of oscillation electric signal transmission cable 4 One end links together with the miniature ultrasonic transducer units 5；The hinge-type fixture 1 provides the work(for facilitating the device to disassemble Energy；Its major function of the miniature ultrasonic transducer units 5 is in the actual sample introduction test of micro-fluidic chip, is launched using it super Sound wave reduces the interfacial tension between sample solution and the inwall of its inner passage of micro-fluidic chip, can be compatible, Also, utilize the sample introduction end 9 and the distance between the terminal 10 and the installation position of miniature ultrasonic transducer units 5 difference And the difference on its ultrasonic intensity for being experienced, its interfacial tension of sample introduction end 9 described in induced synthesis and the terminal 10 Difference between its interfacial tension, the interfacial tension difference between the micro-fluidic chip both ends 9,10 can be in the micro-fluidic chip The both ends 9,10 between form pressure gap, the pressure gap can drive sample solution to be flowed to the direction of terminal 10；Should The ultrasonic wave that miniature ultrasonic transducer units 5 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 8 its Swallow up effect of the body phase to the large biological molecule；It is soft and have the substrate 8 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 10 is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 9；And Micropump 14, should Micropump 14 is connected with the sample introduction end 9；The function of the Micropump 14 is, in the sample solution and its inner passage of micro-fluidic chip Interfacial tension between inwall is reduced, under the increased precondition of alternate compatibility by the ul-trasonic irradiation, with the Micropump 14 The interfacial tension difference come between the both ends 9,10 of ultrasonic wave induction of mechanicalness pumping strength drive caused by it Amount of power is supported mutually, adjusts mutually, is mutually coupled, and is pooled in a manner of Collaboration described in one driving test liquid flow direction The strength of the direction of terminal 10 flowing, is filled with some high hydroscopic resin particles in the terminal liquid pool, its opening end of the terminal liquid pool Covered by breathable microporous film.

Arrow in legend indicate the micro-fluidic chip its in actual motion, by both ends 9,10 pressure differentials drive, The flow direction of its sample liquid stream.

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

The Micropump 14 can customize to specialized factory.

Described its main body of hinge-type fixture can simply be changed a social system using commercially available hinge；Can also be to hardware processing factory Customization.

Involved miniature ultrasonic transducer units 5 are commercially available；It can also be customized to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal transmission cable 4 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 determine to relevant manufacturers System.

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.

This case device is that a variety of corresponding aids antibodies are detected with a variety of AIDS antigens, thereby diagnoses AIDS Disease.

Claims

1. a kind of AIDS diagnosis for being related to hydrophobic substrate multichannel micro-fluidic chip device, the structure of the device includes leading to more Road micro-fluidic chip, the structure of the micro-fluidic chip include being bonded to each other the substrate and cover plate of installing together, the substrate and Cover plate is plate object or tablet, and that face towards the cover plate of the substrate is contained via mould pressing process or etching technics shape Into channel structure, be bonded to each other the substrate that is installed together and be built into the miniflow containing pipeline configuration jointly with the cover plate Chip is controlled, the locations of structures of the pipeline is located at the juncture area that the substrate is bonded to each other with the cover plate, the both ends difference of the pipeline It is connected with the sample introduction end of the micro-fluidic chip and terminal, the sample introduction end is the injection end of the micro-fluidic chip sample solution, should Terminal is the terminal of sample solution flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, the terminal and the sample introduction end phase Mutually remote, between 3 centimetres and 10 centimetres, the terminal contacts with terminal liquid pool for the distance between the terminal and the sample introduction end Together, 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 pipeline stream The sample solution of terminal is moved, is sequentially equiped with working electrode on 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 antigen 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 antigen in its top layer gold size sensitivity membrane structure of four working electrodes is to aids antibody respectively Can specific binding four kinds of AIDS antigenic substances, four kinds of antigenic substances be respectively AIDS specific antigen p24, Gp41, gp120 and gp36, its material of the working electrode are gold material or thermally decompose conducting polymer material, the work Sheet or thread is presented in electrode its pattern, it is characterised in that its material of the substrate is dimethyl silicone polymer material, the substrate its Surface is the surface of primary form, the surface of the primary form its be intended to refer to not by any surface chemical modification or appoint The surface of the primary form of the material of what surface chemical modification, the structure of the device also include hinge-type fixture, the hinge-type Fixture its appearance profile likeness in form hinge, the hinge-type fixture is by two hinges being mutually hinged and through two pages One fastening screw of piece and one match and tight manually with being used for of connecting together of the fastening screw with the fastening screw Gu and the nut of hand break loose is formed, two hinges of the hinge-type fixture are respectively mutually drawn close with its tip and to clamp this micro-fluidic Chip, the tip are positioned in the locations of structures of the neighbouring terminal of the micro-fluidic chip, an institute at least in State attaching fixation in hinge and be equiped with miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, the higher-order of oscillation One end of electric signal transmission cable links together with the miniature ultrasonic transducer units；The hinge-type fixture provides a convenience The function that the device is disassembled；Its major function of the miniature ultrasonic transducer units is the profit in micro-fluidic chip actual sample introduction test The ultrasonic wave launched with it reduces the interfacial tension between sample solution and the inwall of its inner passage of micro-fluidic chip, Can be compatible, also, using between the sample introduction end and the terminal and the miniature ultrasonic transducer units installation position Distance difference and its ultrasonic intensity experienced on difference, its interfacial tension of sample introduction end and institute described in induced synthesis State the difference between terminal its interfacial tension, the interfacial tension difference between the micro-fluidic chip both ends can be in the micro-fluidic core Pressure gap is formed between the both ends of piece, the pressure gap can drive sample solution to the end flow；The miniature ultrasonic The ultrasonic wave that wave transducer its function also includes being launched with it check large biological molecule contained in sample its in the miniflow The absorption on chip its inner passage inner surface is controlled, and then checks the substrate of the dimethyl silicone polymer material its body phase to the life The effect of swallowing up of thing macromolecular；It is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and include with it to super The property that sound wave absorbs strongly, ultrasonic wave is absorbed strongly, and thereby in micro-fluidic chip terminal to the sample introduction end Between limited short distance within realize the rapid decrement of ultrasonic intensity；And Micropump, the Micropump connect with the sample introduction end Connect；The function of the Micropump is, the interfacial tension between the inwall of the sample solution and its inner passage of micro-fluidic chip by The ul-trasonic irradiation and reduce, under the increased precondition of alternate compatibility, come and this with the mechanicalness of Micropump pumping strength Interfacial tension difference its caused driving force between the both ends of ultrasonic wave induction supports mutually, adjustment, mutually mutually It is coupled, the strength that one driving test liquid flows to the terminal direction flowing, the terminal is pooled in a manner of Collaboration Some high hydroscopic resin particles are filled with liquid pool, its opening end of the terminal liquid pool is covered by breathable microporous film.

2. a kind of AIDS diagnosis for being related to hydrophobic substrate multichannel micro-fluidic chip device according to claim 1, Characterized in that, it is capillary channel that the pipeline, which includes the lateral,.

3. a kind of AIDS diagnosis for being related to hydrophobic substrate multichannel micro-fluidic chip device according to claim 1, Characterized in that, the thermal decomposition conducting polymer is the conduction formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated Property material.

4. a kind of AIDS diagnosis for being related to hydrophobic substrate multichannel micro-fluidic chip device according to claim 1, Characterized in that, the width or diameter of the working electrode be between 0.1 micron to 2000 microns, and, the work electricity The length of pole is between 1 micron to 15000 microns.

5. a kind of AIDS diagnosis for being related to hydrophobic substrate multichannel micro-fluidic chip device according to claim 1, Characterized in that, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.

6. a kind of AIDS diagnosis for being related to hydrophobic substrate multichannel micro-fluidic chip device according to claim 1, Characterized in that, the cover plate its material in structure is dimethyl silicone polymer material.

7. a kind of AIDS diagnosis for being related to hydrophobic substrate multichannel micro-fluidic chip device according to claim 1, Characterized in that, the Micropump is miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.

8. a kind of AIDS diagnosis for being related to hydrophobic substrate multichannel micro-fluidic chip device according to claim 1, Characterized in that, described its thickness of cover plate and substrate in structure is between 1.0 millimeters and 5.0 millimeters.

9. a kind of AIDS diagnosis for being related to hydrophobic substrate multichannel micro-fluidic chip device according to claim 1, Characterized in that, the structure of the device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission cable Its other end is connected with the higher-order of oscillation electric signal generator.

10. a kind of AIDS diagnosis for being related to hydrophobic substrate multichannel micro-fluidic chip device according to claim 1, Characterized in that, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units, between 5 milliwatts and 9000 milliwatts, this is micro- The frequency of its ultrasonic wave operationally launched of type ultrasonic transducer is between 100KHz and 12MHz.