CN107081178A

CN107081178A - AIDS diagnosis comprising hydrophobic substrate multichannel micro-fluidic chip device

Info

Publication number: CN107081178A
Application number: CN201610100298.2A
Authority: CN
Inventors: 李榕生; 葛宇杰
Original assignee: Individual
Current assignee: Individual
Priority date: 2016-02-15
Filing date: 2016-02-15
Publication date: 2017-08-22

Abstract

The present invention relates to a kind of AIDS diagnosis multichannel micro-fluidic chip device comprising hydrophobic substrate, belong to analysis testing field.There is technology barrier with dimethyl silicone polymer i.e. PDMS that is cheap and easily processing to make the substrate of AIDS diagnosis micro-fluidic chip；Its surface of the PDMS is strongly hydrophobic, and targetedly surface is modified or surface modification, and its effect is difficult to persistently, and this case aims to solve the problem that the serial relevant issues.This case main points are, the selected PDMS with ecosystem surface of substrate, and fastening is positioned at the test 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, simultaneously, ultrasonic wave damper is installed at the sample introduction end of the micro-fluidic chip, reach ultrasonic intensity rapid decrement in short distance, so as to form interfacial tension difference at the two ends of the chip, thereby facilitate test liquid stream to be flowed along originally hydrophobic capillary channel to the terminal direction.

Description

AIDS diagnosis comprising hydrophobic substrate multichannel micro-fluidic chip device

Technical field

The present invention relates to a kind of AIDS diagnosis multichannel micro-fluidic chip device comprising hydrophobic substrate, belong to analysis test neck Domain.

Background technology

The micro-fluidic AIDS diagnosis technical background of associated multi-channel, may refer to the patent of invention such as CN 200910151219.0 Shen Please case.

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

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

The basic framework of micro-fluidic chip, including it is etched with the substrate of small fluid course and the cover plate fit together therewith, Small fluid course on the substrate, assembling upper cover plate before, it is apparent on see to be exactly some micro-channels, wait until thereon After covering cover plate, just real closure forms the small fluid course, and the conduit inner surface of the micro-channel is together with surround this The part cover plate of micro-channel constitutes described small fluid course together；So, it is clear that this after assembling is completed is small Fluid course, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, in the micro-channel The state or property on surface substantially determine the integrality or property of the small fluid course；Therefore say, this is built in base The inner surface state or inner surface property of micro-channel on piece are key factors；In principle, it is any to keep or protecting substantially The material of its solid forms is held, can be used to make substrate and cover plate, such as, the material that can act as substrate and cover plate can be with It is monocrystalline silicon piece, quartz plate, sheet glass, high polymer such as dimethyl silicone polymer, polymethyl methacrylate, makrolon etc. Deng；Certainly, the selection of substrate and the selection of cover plate be able to can also be differed with identical；From material consumption, manufacture difficulty and From the point of view of in terms of application popularization prospect etc., between these materials exist not small difference, the especially selection of that substrate, influence compared with Greatly.

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

But, thing is really not so simple.

First, this polydimethyl siloxane material, that is, the material that the letter PDMS that abridges is referred to, itself are a kind of strong Hydrophobic material, micro-channel is built on this material, if without being operated for the modified of the micro-channel surface, then, After overall assembling is completed, that is, cover after cover plate, because the micro-channel its inner surface in structure occupies most liquid circulation The inner surface in road, then, its strong hydrophobic property of the PDMS micro-channels inner surface, is deciding factor, it can cause class Be similar to the aqueous solution the fine liquid stream of polar liquid by becoming very difficult, its flow resistance is big, or even general Micropump is all It is 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 Operation；So, this is pretty troublesome for the modified operation of PDMS micro-channel inner surfacesThat falls nor this problem, structure Perplex into serious technical, be another problem：PDMS polymer molecules tool inside its body phase of this PDMS material substrate There are PDMS polymer molecules inside the characteristic for diffusing to the surface, migrating automatically, this substrate body phase to diffuse to the surface, move automatically The characteristic of shifting, will cause the state after modification by its inner surface of that micro-channel of surface modifying and decorating can not maintain foot Enough long time, the holding time for micro-channel its inner surface state after that is surface-modified is substantially only sufficient to complete in laboratory The time of portion's test experiments needs；In other words, by surface modification or the PDMS micro-channel inner surfaces of surface modification, its The surface state that is formed can not be lasting after modification or after saying modification, but soon automatically tend to or say and become surface again and change Surface state before property, returns to the strong hydrophobic surface state of that script in the shorter time, then, just think, Such micro-fluidic chip can largely make, mass storage, be widely popularized, and answer is it is obvious that is, impossible. Micro-channel on this PDMS material, can not pump similar to the fine liquid stream of polar solvent of the aqueous solution if not doing surface modification Send and pass through, chip also cannot just be used；And if having done surface modification, the state after its modification can not be persistently kept again, also Being equally can not popularization and application.

So, how to accomplish that substrate can either be made using cheap PDMS material, and table in the micro-channel can be released Face decorating state can not persistently, chip can not largely make, largely lay in so that be widely popularized it is such a make this area it is numerous specially The puzzlement that industry personnel are entangled with for a long time, the highly difficult problem that exactly one its obvious technology barrier can not despise.

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

Second, the PDMS material of non-surface modification, above it is stated that, its surface is strongly hydrophobic, this strong hydrophobic Material surface and also another problem, that is, this strong hydrophobic PDMS surfaces can adsorb large biological molecule, and And, these adsorbed large biological molecules can also further depression further on PDMS surfaces, gradually fall into gradually deep, directly It is trapped in heavy within the body phase of PDMS substrates, in fact, this process is partly also due to inside PDMS material body phase Polymer molecule, which has, to be diffused to the surface, caused by travel motion；Such case, can also be explained from another angle, i.e. Continuously from inside PDMS body phases to its diffusion into the surface, migration those polymer molecules, its result moved, be by Gradually those are involved within the body phase of PDMS substrates by the large biological molecule of adsorption, briefly, these are inhaled Attached large biological molecule is exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up large biological molecule Phenomenon, the influence caused by it necessarily causes the severe deviations of all kinds of test data of experiment for being related to large biological molecule.

As described above, be the problem of PDMS substrates, its not only adsorption large biological molecule, and swallow up large biological molecule, So, as the large biological molecule of experiment test object, its disappearance will not stop because the absorption of surface saturation, but, no It is disconnected adsorbed, also constantly swallowed up.

On PDMS substrates in related experiment test process its body phase constantly swallow up test associated biomolecule macromolecular phenomenon, separately It is to say that one kind, which is explained, there are substantial amounts of Minute pores in PDMS body phases, and associated biomolecule macromolecular is by after adsorption, depression Into these Minute pores, and then swallowed up；However, inventor thinks, those can allow the air point of miniature scale Son squeezes into the Minute pores therebetween, and being not equal to them also can directly allow that the large biological molecule of relative large scale enters, and two Person's difference on yardstick is huge, must not make sweeping generalizations.Explanation is bypassed, in any case, the biology of object is analyzed as dependence test Macromolecular is adsorbed by PDMS substrate micro-channels inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is known objective The phenomenon of presence.

, can be from containment PDMS surfaces to life in order to prevent this PDMS substrate bodies relative to the effect of swallowing up of large biological molecule The absorption of thing macromolecular is addressed, 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 quilt PDMS substrate body phases are swallowed up；But, or that old problem, that is, the chemical modification on PDMS material surface changes Surface state after property can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface automatically, The process of migration, soon 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 Its micro-channel inner surface of substrate 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, can reach again Growth stage contains absorption process of the PDMS substrate micro-channel inner surfaces to large biological molecule, and then prevents PDMS substrate body phases The effect of swallowing up to large biological molecule so that related chip manufactured goods are able to maintain that a prolonged enough, rational shelf-life, It is exactly a very intractable problem.The problem makes the numerous specialties in this area as another problem addressed above, equally Personnel are entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise.The hardly possible Also be present many year in topic, so far, also not yet properly settled.

The content of the invention

The technical problems to be solved by the invention are to provide a package solution, solve what is addressed above totally Two problems, also, the solution is used into multichannel micro-fluidic chip field applied to AIDS diagnosis, form a kind of new AIDS diagnosis Multichannel device.

The present invention solves the technical problem by following scheme, and the device that the program is provided is a kind of Chinese mugwort for including hydrophobic substrate Disease diagnosis multichannel micro-fluidic chip device is grown, the structure of the device includes multichannel micro-fluidic chip, the micro-fluidic chip Structure includes the substrate and cover plate of installing bonded to each other together, and the substrate and cover plate are plate object or tablet, the substrate That face towards the cover plate contain via mould pressing process or etching technics formation channel structure, the substrate also contain and the groove Road structure is connected and pierces the window structure via the formation of mould pressing process, etching technics or simple drilling technology of the substrate, phase The substrate being mutually jointly mounted to together has been built into containing pipeline configuration and the liquid pool structure being attached thereto jointly with the cover plate Micro-fluidic chip, the locations of structures of the pipeline is located at the substrate and cover plate interface zone bonded to each other, its side of the window Blocked and opposite side opening by the cover plate, the locations of structures of the window is exactly the locations of structures of the liquid pool, the quantity of the liquid pool It it is three, its locations of structures of two liquid pools therein is located at the sample introduction end of the micro-fluidic chip, its structure of remaining liquid pool position The terminal that liquid flows in its chip during sample introduction test actual setting in the micro-fluidic chip, the terminal and the sample introduction end are mutually remote From, the pipeline one end via be similarly positioned in the manifold shape turnout of the interface zone bonded to each other respectively with positioned at sample introduction end should Liang Ge liquid pools UNICOM, the other end of the pipeline and a remaining liquid pool UNICOM for the terminal positioned at the micro-fluidic chip, And, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode and reference electrode, the work Electrode is by conductive electrode and the gold size sensitive membrane structure for having embedded AIDS specific antigen being attached on the conductive electrode Into the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of four lateral parallel connections, the work The quantity of electrode is four, and the installation position of four working electrodes is located in four laterals respectively, and, this four Specific antigen in the sensitive membrane structure of its top layer gold size of individual working electrode is can be specifically bound to aids antibody four respectively AIDS antigenic substance is planted, four kinds of antigenic substances are AIDS specific antigen p24, gp41, gp120 and gp36 respectively, Its material of the working electrode is gold material or thermal decomposition conducting polymer material, the working electrode its pattern present sheet or Thread, emphasis is that its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, should The surface of primary form its be intended to refer to the material not no by any surface chemical modification or any surface chemical modification The surface of primary form, the structure of the device also includes hinge-type fixture, hinge-type fixture its appearance profile likeness in form hinge, should Hinge-type fixture by two hinges being mutually hinged and through a fastening screw of two hinges and one with The nut for being used for fastening and hand break loose manually that the fastening screw is matched and connected together with the fastening screw is constituted, the hinge Two hinges of formula fixture are respectively mutually drawn close with its tip and clamp the micro-fluidic chip, and the tip is positioned at the micro-fluidic chip The neighbouring terminal locations of structures on, attached in a hinge at least in and fixed be equiped with miniature ultrasonic and change Energy device, 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 hinge-type fixture facilitates the function that the device is disassembled there is provided one；The miniature ultrasonic transducer units Its major function be in the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it reduce sample solution with it is described Interfacial tension between the inwall of pipeline, can be compatible, also, miniature with this using the sample introduction end and the terminal Difference in the distance between ultrasonic transducer installation position difference and its ultrasonic intensity experienced, induced synthesis institute State the interface between the difference between its interfacial tension of sample introduction end and the terminal its interfacial tension, the micro-fluidic chip two ends Power difference can form pressure gap between the two ends of the micro-fluidic chip, and the pressure gap can drive sample solution to the end End flowing；Its function of the miniature ultrasonic transducer units also includes checking biology contained in sample greatly with its ultrasonic wave launched Its absorption on the inner surface of pipeline of molecule, and then check the substrate of the dimethyl silicone polymer material its body phase to the biology The effect of swallowing up of macromolecular；Its function of the substrate of the dimethyl silicone polymer material is included with cover plate and working electrode and to electrode It is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function also and reference electrode together builds the micro-fluidic chip Including with its property to the strong absorption of ultrasonic wave, being absorbed strongly to ultrasonic wave, and thereby in the micro-fluidic chip terminal The rapid decrement of ultrasonic intensity is realized within to the limited short distance between the sample introduction end；And, ultrasonic wave damper should Its profile of ultrasonic wave damper is in block, tabular or bar-shaped；Its material of the ultrasonic wave damper be microcellular rubber, sponge rubber or Microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, the medial surface of each clamping limb and another The medial surface of clamping limb is relative, and the medial surface of one of clamping limb is close to the sample introduction end of the micro-fluidic chip, another clamping The medial surface of arm is close to the ultrasonic wave damper, and the elastic clip is surpassed at the sample introduction end of the micro-fluidic chip with this with its gripping strength Sound wave damper is clipped together bonded to each otherly, and the strong abatement to ultrasonic wave that the ultrasonic wave damper is brought with its material is made With further support realizes ultrasonic intensity within micro-fluidic chip terminal to the limited short distance between the sample introduction end Rapid decrement, and thereby further expand the difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension.

Described miniature ultrasonic transducer units can certainly be all installed in two hinges；But, only installing one is micro- Type ultrasonic transducer is dealt with enough to be used.

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

The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and AIDS specific antigen solution uniformly, uses point sample Instrument point sample is coated on specified structure position, and forms its drying and forming-film.AIDS disease-specific in the gold size sensitive membrane resists Original is the AIDS antigen of horseradish peroxidase or glucose oxidase mark, and the gold size sensitive membrane has been included as fixing Above-mentioned each AIDS specific antigen and introduce complementary medium therein, the complementary medium such as chitosan, acetate fiber Element, gelatin is therein a kind of or their mixture.

The pipeline and the lateral and the manifold shape turnout in the microfluidic chip structure, its internal diameter chi It is very little to may each be arbitrarily selected size, still, use the consideration in terms of prepare liquid sample and reduction reagent loss less for trying one's best, The passage of capillary level, the capillary level are preferably selected in the pipeline and the lateral and the manifold shape turnout Passage imply that its internal diameter passage suitable with the internal diameter of the capillary on ordinary meaning.Its inner passage of capillary it is transversal Face shape can be arbitrary shape, the shape of cross section is for example circular, oval, square, rectangle, bar shaped, certainly Can be arbitrarily exist bending it is linear, also, the capillary interior shape with the extension of pipeline, different parts Shape of cross section can also allow to be different shapes.Only for the word of capillary one, its art-recognized meanings is known.

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

It is related to several liquid pools in this case microfluidic chip structure, the liquid pool is the pond shape or scrotiform structure for transitional liquid storage Make, its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, the cavity shape such as cylindrical empty Cavity-like, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..The size of the liquid pool can be arbitrarily selected Size, still, in order to use prepare liquid sample and reduction reagent loss less as far as possible, the liquid pool is preferably capable of and capillary The liquid pool of the microminiature of matching.

It is public only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field Know.

Various sizes, variously-shaped ultrasonic transducer are commercially available；Commercially available miniature ultrasonic transducer units its sizes can be with It is small to the magnitude only calculated with millimeter.

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

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

The industrial products market of involved its all size of higher-order of oscillation electric signal transmission cable is on sale.

The structure of the device can also include higher-order of oscillation electric signal generator；Its is another for the higher-order of oscillation electric signal transmission cable One 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, for the professional in ultrasonic technology field, be It is simple and known；The higher-order of oscillation electric signal generator can be customized to ultrasonic instrument specialized factory.

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

This case device can further include some annexes, the annex such as multiple tracks electrochemical workstation etc., institute certainly The art-recognized meanings for stating multiple tracks electrochemical workstation are known.Each working electrode for being related in this case microfluidic chip structure and , can be respectively via corresponding special the corresponding interface got lines crossed with the multiple tracks electrochemical workstation to electrode and reference electrode etc. Coupled.It is described that special to get lines crossed be for each the corresponding interface of each electrode and the multiple tracks electrochemical workstation is carried out into phase The private cable being mutually coupled with.The micro-fluidic chip in this case device, its structure can also include micro-valve, the number of the micro-valve Amount is not limited, according to actual needs, and the micro-valve can be installed in any required position installed in the microfluidic chip structure； The word of micro-valve one is for the professional of micro fluidic chip technical field, and the art-recognized meanings of itself are known；The micro-valve The manufacturing technology of itself and the use of technology is also known；The component that the micro-valve is not required.

The diameter of the working electrode can allow to be that any setting is easily installed the suitable diameter used, it is however recommended to Or say preferred its scope of the diameter between 0.1 micron to 2000 microns；The length of the working electrode can permit Permitted to be that any setting is easily installed the length used, it is however recommended to or to say preferred its scope of the length be at 1 micron To between 15000 microns.

The gold size for being installed in the working electrode surface layer by spraying or point sample instrument point sample or the coating of other appropriate process is quick Feel film, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness, still, push away Preferred thickness is between 10 nanometers and 200 nanometers in other words for the thickness recommended.

The cover plate in chip structure, its material can allow to be any electrical insulating property material, for example：Polypropylene, glass Glass, polymethyl methacrylate, dimethyl silicone polymer, etc., in order to make smaller size of micro-fluidic chip, such as do Realized into the micro-fluidic chip of only 2.0 centimetres to 3.0 centimetres of super-small of length, and 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 It is used as the cover plate using dimethyl silicone polymer, is also that this case technical scheme is allowed.

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

Described its thickness of cover plate and substrate can allow be any setting be easy to assembling thickness, the thickness of recommendation or say preferably Thickness be between 1.0 millimeters and 5.0 millimeters.Less thickness is conducive to saving material.

Described its size of ultrasonic wave damper is not limited, and described its length of ultrasonic wave damper, width, thickness may each be basis Need the arbitrary size of setting.

It is known in field of rubber technology only for the word of microcellular rubber one art-recognized meanings of itself.

The microcellular rubber is commercially available.

It is known in field of rubber technology only for the word of sponge rubber one art-recognized meanings of itself.

The sponge rubber is commercially available.

It is known in technical field of macromolecules only for the word of microporous polyurethane elastomer one art-recognized meanings of itself.

The polyurethane micropore elastomer material is commercially available.

The microcellular rubber preferred microporous silicon rubber or micropore fluorubber.

It is known in field of rubber technology only for the word of micropore silicon rubber one art-recognized meanings of itself.

The microporous silicon Rubber market is on sale.

It is known in field of rubber technology only for the word of micropore fluorubber one art-recognized meanings of itself.

The micropore fluorubber is commercially available.

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

The elastic clip is commercially available.

The application method of this case micro-fluidic chip：

Proposed first based on this case and the first public New stream driving principle, its application running of this case micro-fluidic chip In, the New stream driving method is determined completely without involving any additional Micropump.

The interfacial tension difference of this case to be formed between micro-fluidic chip two ends caused by the ultrasonic wave, drives liquid Stream flows in the capillary channel of the four-way micro-fluidic chip, using four-way electrochemical analytical instrument respectively to four kinds of AIDS Sick antibody is detected.

Corresponding four kinds of aids antibodies are detected with four kinds of AIDS antigens, with detecting corresponding four with four kinds of aids antibodies AIDS antigen is planted, similarly, can diagnosis of aids；The principle of its foundation is necessarily resisted in AIDS patient Former, antibody is simultaneously deposited, and mutually Reversible binding, is formed reversible conjugate, therefore, antibody is detected with antigen and is thereby diagnosed AIDS, with removing detecting antigen and diagnosis of aids with antibody, can reach diagnostic purpose.Certainly, its phase of different means The electrode sensitive decorative layer answered technically and is differed.

The specific detection of this case micro-fluidic chip is as follows using step：

1st, blood serum sample liquid is added in micro-pipe road, under ultrasonic wave driving, various aids antibody molecules are by each passage The AIDS specific antigen capture for the corresponding horseradish peroxidase-labeled that gold size sensitive membrane is embedded on middle electrode surface.

2nd, the aids antibody in the AIDS specific antigen and blood serum sample of horseradish peroxidase-labeled forms immune compound Thing.

3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, using the above-mentioned reaction of amperometric detection Caused curent change, 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 fixture in the terminal of the micro-fluidic chip, with The miniature ultrasonic transducer units installed, the low-power launched using it, high-frequency band are attached in its hinge of the hinge-type fixture Ultrasonic wave so that without surface chemical modification or surface chemical modification strong hydrophobic micro-fluidic chip internal pipeline its Compatibility between tube wall and the test object aqueous solution is significantly increased, and this passes through possible there is provided a reality for test liquid stream Property；Meanwhile, using its strong absorbability to ultrasonic wave of dimethyl silicone polymer substrate, in shorter distance, also Be, from the terminal to the very short distance of only several centimeters yardsticks the sample introduction end in, reach the quick of ultrasonic intensity Successively decrease, the difference of the interfacial tension is thereby caused at the two ends of the micro-fluidic chip, and then, using between the two ends Pressure gap between its two ends for being formed of the difference of interfacial tension, driving test liquid stream is strongly hydrophobic in such a script Capillary channel in the terminal direction flow.By this case liquid stream drive scheme, entirely without must be to the polydimethylsiloxanes The substrate and its internal pipeline of alkane material carry out any surface chemical modification or chemical modification, have altogether dispensed with the surface chemistry and have repaiied The laborious procedures of decorations or chemical modification；And altogether dispense with the equipment of traditional Micropump etc；On the other hand, this is low The ultrasonic wave of power, high-frequency band, additionally it is possible to contain the large biological molecule in sample in the literalness naked polydimethylsiloxanes Absorption on its inner surface of pipeline of alkyl piece, and then contain its body phase of the dimethyl silicone polymer substrate to the large biological molecule The effect of swallowing up；The Reversible binding thing of the antigen, antibody and antigen and antibody is all to belong to described large biological molecule certainly Type；Because described suction-operated and the described effect of swallowing up effectively are contained that therefore, dependence test result will more Actual conditions can objectively be reflected；The effect of the low-power, high-frequency band ultrasonic wave, also includes facilitating antigen, antibody certainly Between Reversible binding reaction quick reaching, this causes dependence test operation can be to be completed than faster speed.

Due to the surface chemical modification for the dimethyl silicone polymer substrate its relevant surfaces or chemical modification behaviour need not be carried out Make, therefore, this surface chemical modification layer or chemically modified layer not need to exist, then, the dimethyl silicone polymer Its body phase interior polymer molecule of substrate constantly diffuses to the surface automatically, migrate caused by it to surface chemical modification layer or The damaging influence of chemically modified layer is also just not present.

This case its installation position is located at the ultrasonic wave damper at the sample introduction end, from its terminal of this case micro-fluidic chip to Said on the sport technique segment that ultrasonic intensity rapid decrement is realized in the such short distance in sample introduction end, its effect of the ultrasonic wave damper is suitable In the size expansion device of micro-fluidic chip, in other words, the ultrasonic wave damper its function as and significantly extend miniflow Its terminal of chip is controlled the distance between to sample introduction end, is the equal of from several centimetres of extension of script to more than ten centimetres of length Or twenties centimetres of length or longer length, so so that described terminal to the ultrasonic wave between sample introduction end in short distance The sport technique segment of intensity rapid decrement can relatively easily be reached, also, the size expansion device namely the ultrasonic wave damper Its installation and removal is all very convenient, it is important that it can also be reused.

The technical scheme of this case has dissolved its application related one to dimethyl silicone polymer substrate addressed above totally Row technical barrier.Based on this case scheme, this kind very cheap polydimethyl siloxane material is just possible in the micro-fluidic chip 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, and the structure is provided One facilitates the function that the device is disassembled, in this way, the hinge-type fixture is together with appended miniature ultrasonic transducer units in its hinge Just easily it can be mutually disengaged with the micro-fluidic chip, then, the component that the part can freely depart from just can circulate benignly ground Reuse many times；The architectural feature is conducive to saving the use cost of the device.

Brief description of the drawings

Fig. 1 is the schematic diagram of this case device embodiment chip part construction, it is shown that the depression angle of this structure Under chip internal pipeline and each electrode and each related liquid pool structural form, do not depict in the figure hinge-type fixture with And its miniature ultrasonic transducer units set up in hinge and other annexes.

Fig. 2 is its rough outside side view of this case device.

In figure, 1,2,10 be the different liquid pool of three installation positions respectively, and 3 be manifold shape turnout, 4,7,11,14 It is that installation position is different but four laterals parallel with one another for forming UNICOM's structure in parallel respectively, 5 be to be installed in lateral 4 The working electrode that specific antigenic substance in the interior sensitive membrane structure of its top layer gold size is AIDS specific antigen p24,6 are Specific antigenic substance in the sensitive membrane structure of its top layer gold size being installed in lateral 7 is AIDS specific antigen Gp41 working electrode, 12 be the specific antigen thing in the sensitive membrane structure of its top layer gold size being installed in lateral 11 Matter is AIDS specific antigen gp120 working electrode, and 13 be that its top layer gold size being installed in lateral 14 is sensitive The working electrode that specific antigenic substance in membrane structure is AIDS specific antigen gp36,8 be that, to electrode, 9 be reference Electrode, 15 be hinge-type fixture, and 16 indicate linkwork positions, and 17 be fastening screw, and 18 be higher-order of oscillation telecommunication Number transmission cable, 19 be miniature ultrasonic transducer units, and 20,25 be two different hinges of locations of structures respectively, and 21 be lid Piece, 22 be substrate, and 23 be sample introduction end, and 24 be terminal, and 26 be nut；The hinge-type clamp structure in legend only shows The legend structure of meaning, actual its structure of the hinge-type fixture is not limited to the legend hinge-type clamp structure；Arrow in legend Indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, the flow direction of its test liquid stream.

The ultrasonic wave damper is depicted without in legend；Also the elastic clip is depicted without in legend.

Embodiment

In this case that Fig. 1 and Fig. 2 are shown embodiment, the structure of the device includes multichannel micro-fluidic chip, and this is micro- The structure of fluidic chip includes the substrate 22 and cover plate 21 of installing bonded to each other together, and the substrate 22 and cover plate 21 are Contain what is formed via mould pressing process or etching technics in plate object or tablet, that face towards the cover plate 21 of the substrate 22 Channel structure, the substrate 22 also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics Or the window structure of simple drilling technology formation, substrate 22 bonded to each other being installed together is built into jointly with the cover plate 21 Micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the liquid pool is liquid pool 1, liquid pool 2, liquid pool 10, the locations of structures of the pipeline is located at the substrate 22 and the cover plate 21 interface zone bonded to each other, and its side of the window is by this Cover plate 21 is blocked and opposite side is opened, and the locations of structures of the window is exactly the structure position of the liquid pool 1, liquid pool 2, liquid pool 10 Put, the quantity of the liquid pool is three, two liquid pools therein are liquid pool 1 and its locations of structures of liquid pool 2 positioned at the micro-fluidic core The sample introduction end 23 of piece, a remaining liquid pool is that liquid pool 10 its locations of structures is located at when the actual sample introduction of the micro-fluidic chip is tested it The terminal 24 that liquid flows in chip, the terminal 24 is located remotely from each other with the sample introduction end 23, and one end of the pipeline is via same position In the manifold shape turnout 3 of the interface zone bonded to each other respectively with the liquid pool 1 positioned at sample introduction end 23 and the UNICOM of liquid pool 2, A remaining liquid pool for the terminal 24 of the other end of the pipeline with being located at the micro-fluidic chip is the UNICOM of liquid pool 10, with And, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode 8 and reference electrode 9, the work Make electrode by conductive electrode and the gold size sensitive membrane for having embedded AIDS specific antigen being attached on the conductive electrode Constitute, the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of four lateral parallel connections, the work The quantity for making electrode is four, and the installation position of four working electrodes is located in four laterals respectively, four works It is working electrode 5, working electrode 6, working electrode 12, working electrode 13 respectively to make electrode, and, four working electrodes Specific antigen in the sensitive membrane structure of its top layer gold size is that the four kinds of AIDS that can be specifically bound to aids antibody resist respectively Original matter, four kinds of antigenic substances are AIDS specific antigen p24, gp41, gp120 and gp36 respectively, are specifically opened up Come and say, 5 be that specific antigenic substance in the sensitive membrane structure of its top layer gold size being installed in lateral 4 is special for AIDS Specific Antigen p24 working electrode, 6 be that specificity in the sensitive membrane structure of its top layer gold size being installed in lateral 7 resists Original matter is AIDS specific antigen gp41 working electrode, and 12 be that its top layer gold size being installed in lateral 11 is quick Feel the working electrode that the specific antigenic substance in membrane structure is AIDS specific antigen gp120,13 be to be installed in branched pipe The specific antigenic substance in the sensitive membrane structure of its top layer gold size in road 14 is electric for AIDS specific antigen gp36 work Pole, the working electrode 5, working electrode 6, working electrode 12, working electrode 13 its material are gold material or thermal decomposition Conducting polymer material, the working electrode 5, working electrode 6, working electrode 12, its pattern presentation piece of working electrode 13 Shape is thread, and emphasis is, its material of the substrate 22 is dimethyl silicone polymer material, and its surface of substrate 22 is primary shape The surface of state, the surface of the primary form its be intended to refer to not pass through any surface chemical modification or any surface chemical modification The material primary form surface, the structure of the device also includes hinge-type fixture 15, its profile of the hinge-type fixture 15 Profile is similar to hinge, and the hinge-type fixture 15 is by two hinges 20,25 for being mutually hinged and through two pages One fastening screw 17 of piece 20,25 and one match with the fastening screw 17 and are socketed in one with the fastening screw 17 The nut 26 for being used for fastening and hand break loose manually risen is constituted, and two hinges 20,25 of the hinge-type fixture 15 are each with it Tip is mutually drawn close and clamps the micro-fluidic chip, and the tip is positioned at the knot of the neighbouring terminal 24 of the micro-fluidic chip Fixation is attached on structure position, in a hinge at least in be equiped with miniature ultrasonic transducer units, this legend, is Attached in hinge 20 and install the miniature ultrasonic transducer units 19, it is of course also possible to allow in two hinges 20,25 all Miniature ultrasonic transducer units in installing, but, it is, in general, that attaching one miniature ultrasonic of installing only in a hinge Transducer is just enough to deal with to be actually needed, and, higher-order of oscillation electric signal transmission cable 18, higher-order of oscillation electric signal transmission One end of cable 18 links together with the miniature ultrasonic transducer units 19；The hinge-type fixture 15 provides a convenience should The function that device is disassembled；Its major function of the miniature ultrasonic transducer units 19 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 the pipeline, can be compatible, and And, utilize the distance between the sample introduction end 23 and the terminal 24 and the installation position of miniature ultrasonic transducer units 19 difference Difference on different and its ultrasonic intensity for being experienced, its interfacial tension of sample introduction end 23 described in induced synthesis and the terminal Difference between 24 its interfacial tension, micro-fluidic chip two ends are that the interfacial tension between sample introduction end 23 and terminal 24 is poor Different can be to form pressure gap between sample introduction end 23 and terminal 24 at the two ends of the micro-fluidic chip, and the pressure gap can drive Dynamic sample solution flows to the direction of terminal 24；Its function of the miniature ultrasonic transducer units 19 also includes what is launched with it Ultrasonic wave checks in sample contained large biological molecule its absorption on the inner surface of pipeline, and then checks the poly dimethyl Swallow up effect of its body phase of the substrate 22 of siloxanes material to the large biological molecule；The substrate of the dimethyl silicone polymer material 22 its function include and cover plate 21 and working electrode 5, working electrode 6, working electrode 12, working electrode 13 and to electrode 8 And reference electrode 9 together builds the micro-fluidic chip, the substrate 22 of the dimethyl silicone polymer material that is soft and having elasticity its Function is also included with its property to the strong absorption of ultrasonic wave, and ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic chip The terminal 24 is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 23；And, surpass Sound wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；Its material of the ultrasonic wave damper is micropore rubber Glue, sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, each clamping limb Medial surface is relative with the medial surface of another clamping limb, and the medial surface of one of clamping limb is close to the sample introduction of the micro-fluidic chip End 23, the medial surface of another clamping limb is close to the ultrasonic wave damper, and the elastic clip is micro-fluidic by this with its gripping strength The sample introduction end 23 of chip and the ultrasonic wave damper are clipped together bonded to each otherly, and the ultrasonic wave damper is brought with its material The strong consumption to ultrasonic wave, further support between the micro-fluidic chip terminal 24 arrives the sample introduction end 23 The rapid decrement of ultrasonic intensity is realized within limited short distance, and thereby further expands described its interface of sample introduction end 23 Difference between power and the terminal 24 its interfacial tension.

It is depicted without being also depicted without the elastic clip in the ultrasonic wave damper, legend in legend.

Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, its test liquid The flow direction of stream.

It is depicted without attaching the miniature ultrasonic transducer units of installing in Fig. 1 in the hinge-type fixture 15 and one hinge 19 and higher-order of oscillation electric signal transmission cable 18；Also, the higher-order of oscillation electric signal is depicted without in Fig. 1 and Fig. 2 The associate member such as generator and multiple tracks electrochemical workstation.

Involved hinge-type fixture 15 can be carried out simply cutting using commercially available hinge, changed a social system；The miniature ultrasonic transducing Device 19 is commercially available；Commercially available miniature ultrasonic transducer units are various in style, can select to use as needed；The miniature ultrasonic Wave transducer 19 can also be customized to ultrasonic transducer specialized factory.

Involved higher-order of oscillation electric signal transmission cable 18 is commercially available；Can also be to ultrasonic transducer producer or cable special manufacturer Family's customization.

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

Each working electrode in this example structure and electrode and reference electrode via each special cable or can be said respectively Get lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as annex or saying interface connection of getting lines crossed.

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

Claims

1. including the AIDS diagnosis multichannel micro-fluidic chip device of hydrophobic substrate, the structure of the device includes multichannel miniflow Chip is controlled, the structure of the micro-fluidic chip includes the substrate and cover plate of installing bonded to each other together, and the substrate and cover plate are Contain the conduit knot via mould pressing process or etching technics formation in plate object or tablet, that face towards the cover plate of the substrate Structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or simply punch The window structure of technique formation, substrate bonded to each other being installed together and the cover plate be built into jointly containing pipeline configuration with And the micro-fluidic chip for the liquid pool structure being attached thereto, the locations of structures of the pipeline is positioned at the substrate and cover plate boundary bonded to each other Face region, its side of the window is blocked by the cover plate and opposite side is opened, and the locations of structures of the window is exactly the structure of the liquid pool Position, the quantity of the liquid pool is three, and its locations of structures of two liquid pools therein is located at the sample introduction end of the micro-fluidic chip, remaining Under liquid pool its locations of structures terminal that liquid flows in its chip when being located at the actual sample introduction test of the micro-fluidic chip, the end End is located remotely from each other with the sample introduction end, and one end of the pipeline is via the manifold shape turnout point for being similarly positioned in the interface zone bonded to each other Not with the Liang Ge liquid pools UNICOM positioned at sample introduction end, this of the terminal of the other end of the pipeline with being located at the micro-fluidic chip is remaining Under a liquid pool UNICOM, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode and Reference electrode, the working electrode is resisted by conductive electrode and the AIDS disease-specific that embedded being attached on the conductive electrode Former gold size sensitive membrane is constituted, and the construction of the pipeline is in parallel construction, the pipeline in parallel construction by four laterals simultaneously Connection is constituted, and 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 the sensitive membrane structure of its top layer gold size of four working electrodes is to aids antibody energy respectively 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 is gold material or thermal decomposition conducting polymer material, the working electrode Sheet or thread is presented in its pattern, it is characterised in that its material of the substrate is dimethyl silicone polymer material, its surface of the substrate The surface of primary form, the surface of the primary form its be intended to refer to not pass through any surface chemical modification or any surface The surface of the primary form of the material of chemical modification, the structure of the device also includes hinge-type fixture, and the hinge-type fixture is outside it Shape profile is similar to hinge, and the hinge-type fixture is tight by two hinges being mutually hinged and through one of two hinges Gu screw and one match with the fastening screw and fastened manually and hand break loose with being used for of connecting together of the fastening screw Nut constitute, two hinges of the hinge-type fixture are respectively mutually drawn close with its tip and clamp the micro-fluidic chip, the tip It is positioned in the locations of structures of the neighbouring terminal of the micro-fluidic chip, attaches and fix in a hinge at least in Miniature ultrasonic transducer units are equiped with, and, higher-order of oscillation electric signal transmission cable, the higher-order of oscillation electric signal transmission cable One end links together with the miniature ultrasonic transducer units；The hinge-type fixture facilitates the function that the device is disassembled there is provided one； Its major function of the miniature ultrasonic transducer units be in the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it come Reduce the interfacial tension between the inwall of sample solution and the pipeline, can be compatible, also, using the sample introduction end with And the distance between the terminal and the miniature ultrasonic transducer units installation position difference and its ultrasonic intensity experienced On difference, the difference between its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension, the micro-fluidic core Interfacial tension difference between the piece two ends can form pressure gap between the two ends of the micro-fluidic chip, the pressure gap meeting Sample solution is driven to the end flow；Its function of the miniature ultrasonic transducer units also includes checking with its ultrasonic wave launched Its absorption on the inner surface of pipeline of contained large biological molecule in sample, and then check the dimethyl silicone polymer material Swallow up effect of its body phase of substrate to the large biological molecule；Its function of the substrate of the dimethyl silicone polymer material includes and lid Piece and working electrode and the micro-fluidic chip is together built to electrode and reference electrode, soft polydimethylsiloxanes for simultaneously having elasticity The substrate of alkane material its function also includes, with its property to the strong absorption of ultrasonic wave, ultrasonic wave being absorbed strongly, and thereby The rapid decrement of ultrasonic intensity is realized within micro-fluidic chip terminal to the limited short distance between the sample introduction end；With And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；Its material of the ultrasonic wave damper is Microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, each folder The medial surface of gripping arm is relative with the medial surface of another clamping limb, and the medial surface of one of clamping limb is close to the micro-fluidic chip Sample introduction end, the medial surface of another clamping limb is close to the ultrasonic wave damper, and the elastic clip is with its gripping strength by the miniflow Sample introduction end and the ultrasonic wave damper for controlling chip are clipped together bonded to each otherly, what the ultrasonic wave damper was brought with its material Strong consumption to ultrasonic wave, is further supported in micro-fluidic chip terminal to the limited short distance between the sample introduction end The rapid decrement of ultrasonic intensity is realized within, and thereby further expand described its interfacial tension of sample introduction end and the terminal its Difference between interfacial tension.

2. the AIDS diagnosis multichannel micro-fluidic chip device according to claim 1 comprising hydrophobic substrate, its feature It is, the pipeline and the lateral and the manifold shape turnout are capillary channel.

3. the AIDS diagnosis multichannel micro-fluidic chip device according to claim 1 comprising hydrophobic substrate, its feature Be, the thermal decomposition conducting polymer be by polyimides or polyacrylonitrile be heat-treated through anoxybiotic after the conductive material that is formed.

4. the AIDS diagnosis multichannel micro-fluidic chip device according to claim 1 comprising hydrophobic substrate, its feature Be, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the working electrode Length is between 1 micron to 15000 microns.

5. the AIDS diagnosis multichannel micro-fluidic chip device according to claim 1 comprising hydrophobic substrate, its feature It is, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.

6. the AIDS diagnosis multichannel micro-fluidic chip device according to claim 1 comprising hydrophobic substrate, its feature It is, its material of the cover plate in structure is dimethyl silicone polymer material.

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

8. the AIDS diagnosis multichannel micro-fluidic chip device according to claim 1 comprising hydrophobic substrate, its feature It is, the microcellular rubber is micropore silicon rubber or micropore fluorubber.

9. the AIDS diagnosis multichannel micro-fluidic chip device according to claim 1 comprising hydrophobic substrate, its feature It is, the structure of the device also includes higher-order of oscillation electric signal generator, its other end of the higher-order of oscillation electric signal transmission cable It is connected with the higher-order of oscillation electric signal generator.

10. the AIDS diagnosis multichannel micro-fluidic chip device according to claim 1 comprising hydrophobic substrate, its feature It is, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 5 milliwatts and 9000 milliwatts, and this is miniature super The frequency of its ultrasonic wave operationally launched of acoustic wave transducer is between 100KHz and 12MHz.