CN107115901A

CN107115901A - The AIDS diagnosis micro flow control chip device that operating mode is coupled based on dual drive

Info

Publication number: CN107115901A
Application number: CN201610116705.9A
Authority: CN
Inventors: 李榕生; 葛宇杰
Original assignee: Individual
Current assignee: Individual
Priority date: 2016-02-25
Filing date: 2016-02-25
Publication date: 2017-09-01

Abstract

The present invention relates to a kind of AIDS diagnosis micro flow control chip device that operating mode is coupled based on dual drive, belong to analysis testing field.The substrate of AIDS diagnosis micro-fluidic chip is made with dimethyl silicone polymer i.e. PDMS that is cheap and easily processing, there is serial problem；This case is directed to the serial problem.This case main points are, the selected PDMS with ecosystem surface of substrate, and its neighbor positions fixes installing miniature ultrasonic transducer units in the test liquid stream terminal of the micro-fluidic chip, 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, difference offer is a kind of to drive the strength that test liquid stream flows along hydrophobic capillary channel to the terminal direction, the strength with Micropump its mechanicalness pumping strength for being included in structure while intercouple, this case solves the serial problem thereby totally.

Description

The AIDS diagnosis micro flow control chip device that operating mode is coupled based on dual drive

Technical field

The present invention relates to a kind of AIDS diagnosis micro flow control chip device that operating mode is coupled based on dual drive, belong to analysis and survey Examination field.

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 to 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.

Third, as described above, the PDMS micro-channel inner surfaces are strongly hydrophobic, and targetedly surface chemical modification or come to the surface Learn modification to be difficult to again persistently, therefore, actually can only still belong to effective short in the surface state after the modification of its surface or surface modification It is used within phase；If have passed through that ofer short duration period of validity, and still by force if use, due to surface shape State already again close to hydrophobic state, is then certainly existed than larger flow resistance using usual Micropump driving test liquid stream, So, just test liquid can only be forced to flow to target direction flowing by increasing Micropump pump power and pumping pressure, as described above, This PDMS material is soft, pumps test liquid stream with too high, machinery pumping pressure, causing the substrate, it enters Bubbling, expanded, distortion, deformation, also, this high-pressure situations occur for the micro-channel that sample end includes sample introduction end near zone Under, also easily occur the stripping between substrate and cover plate, this feelings in the sample introduction end and its micro-channel of near zone and its periphery Under shape, sample solution flows in the crack of the appearance between the substrate and cover plate that are formed after the entrance stripping everywhere, this reality Border causes the damage of the micro-fluidic chip；Certainly, it is not in place if surface modification or surface modification script, also result in There is said circumstances within the of short duration usual term of validity；It is above-mentioned in the case where carrying out liquid stream driving using additional Micropump merely The problem exists all the time.If be modified or the pre action such as surface modification as described above, not doing any surface completely, So, the above-mentioned problem will be even more serious, even without occur micro-channel bubbling described in sample introduction end and its near zone, it is expanded, Between distortion, deformation and substrate and cover plate the problems such as peel off, merely because the flow resistance is excessive, using high pressure Micropump also not Test liquid stream must can be driven to be marched forward towards terminal side.

The content of the invention

The technical problems to be solved by the invention are to provide a package solution, while solving three addressed above The a series of problem actually mutually involved together of aspect, also, the solution is used many applied to AIDS diagnosis Channel microfluidic chip field, forms a kind of new AIDS diagnosis multichannel micro-fluidic chip device.

The present invention solves the technical problem by following scheme, and the device that the program is provided is a kind of AIDS diagnosis with being based on Dual drive couples the micro flow control chip device of operating mode, and the structure of the device includes multichannel micro-fluidic chip, the micro-fluidic core The structure of piece includes the substrate and cover plate of installing bonded to each other together, and the substrate and cover plate are plate object or tablet, are somebody's turn to do The channel structure via mould pressing process or etching technics formation is contained in that face towards the cover plate of substrate, bonded to each other to be arranged on The substrate together has been built into the micro-fluidic chip containing pipeline configuration jointly with the cover plate, and the locations of structures of the pipeline is located at should Substrate and cover plate juncture area bonded to each other, the two ends of the pipeline connect with the sample introduction end of the micro-fluidic chip and terminal respectively Connect, the sample introduction end is the injection end of the micro-fluidic chip sample solution, when the terminal is the micro-fluidic chip actual sample introduction test its The terminal that sample solution flows in chip, the terminal is located remotely from each other with the sample introduction end, and the distance between the terminal and the sample introduction end are situated between Between 3 centimetres and 10 centimetres, working electrode is sequentially equiped with diverse location in the pipeline and to electrode and reference Electrode, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded AIDS specific antigen Gold size sensitive membrane is constituted, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by four laterals structure in parallel Into, the quantity of the working electrode is four, and the installation position of four working electrodes is located in four laterals respectively, And, the specific antigen in the sensitive membrane structure of its top layer gold size of four working electrodes is respectively can specificity to aids antibody With reference to four kinds of AIDS antigenic substances, four kinds of antigenic substances are AIDS specific antigen p24, gp41, gp120 respectively And gp36, its material of the working electrode is gold material or thermal decomposition conducting polymer material, its pattern of the working electrode Sheet or thread is presented, emphasis is that its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is primary form Surface, the surface of the primary form its be intended to refer to not by any surface chemical modification or any surface chemical modification The surface of the primary form of the material, the structure of the device also includes miniature ultrasonic transducer units, and, higher-order of oscillation electric signal Transmission cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable link together, and this is miniature super Acoustic wave transducer is installed in the position of the cover plate of the micro-fluidic chip or the neighbouring terminal of substrate with attaching；The miniature ultrasonic Its major function of transducer is that in the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it reduces sample solution Interfacial tension between the inwall of its inner passage of micro-fluidic chip, can be compatible, also, utilizes the sample introduction end And the distance between the terminal and the miniature ultrasonic transducer units installation position difference and its ultrasonic wave experienced it is strong Difference between difference on degree, its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension, this is micro-fluidic Interfacial tension difference between the chip two ends can form pressure gap between the two ends of the micro-fluidic chip, the pressure gap Sample solution can be driven to the end flow；Its function of the miniature ultrasonic transducer units also includes holding back with its ultrasonic wave launched Only its absorption on the micro-fluidic chip its inner passage inner surface of large biological molecule contained in sample, and then check this and gather Swallow up effect of its body phase of the substrate of dimethyl siloxane material to the large biological molecule；The poly dimethyl silicon that is soft and having elasticity The substrate of oxygen alkane material its function 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, Micropump, the Micropump is connected with the sample introduction end；The function of the Micropump is, in the sample solution and the micro-fluidic chip inside it Interfacial tension between the inwall of passage is reduced by the ul-trasonic irradiation, under the increased precondition of alternate compatibility, micro- with this Its driving force for being brought of interfacial tension difference between the two ends that are induced come the ultrasonic wave of mechanicalness pumping strength of pump Amount is supported mutually, adjusts mutually, is mutually coupled, and one driving test liquid is pooled in the way of Collaboration and flows to the terminal The strength of direction flowing；Described its thickness of cover plate and substrate is between 1.0 millimeters and 5.0 millimeters；And, ultrasonic wave disappears Subtract device, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；Its material of the ultrasonic wave damper is microcellular rubber, sea Continuous rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, the medial surface of each clamping limb Relative with the medial surface of another clamping limb, the medial surface of one of clamping limb is close to the sample introduction end of the micro-fluidic chip, separately The medial surface of one clamping limb is close to the ultrasonic wave damper, and the elastic clip is with its gripping strength by the sample introduction of the micro-fluidic chip End with the ultrasonic wave damper it is bonded to each other clip together, the ultrasonic wave damper with its material brought to the strong of ultrasonic wave Strong consumption, further supports that realization is super within micro-fluidic chip terminal to the limited short distance between the sample introduction end The rapid decrement of intensity of acoustic wave, and thereby further expand between described its interfacial tension of sample introduction end and the terminal its interfacial tension Difference.

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

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

The Micropump such as miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.

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

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

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

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

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

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

The involved higher-order of oscillation electric signal generator technology of itself, for the professional in ultrasonic technology field, 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 2 milliwatts and 2000 milliwatts it Between；The preferred scope of the frequency of its ultrasonic wave operationally launched of the miniature ultrasonic transducer units be between 100KHz with Between 12MHz.

This case device can further include some annexes, the annex such as multiple tracks electrochemical workstation etc., institute certainly The art-recognized meanings for stating multiple tracks electrochemical workstation are known.Each working electrode for being related in this case microfluidic chip structure and , can be respectively via corresponding special the corresponding interface got lines crossed with the multiple tracks electrochemical workstation to electrode and reference electrode etc. Coupled.It is described that special to get lines crossed be for each the corresponding interface of each electrode and the multiple tracks electrochemical workstation is carried out into phase The private cable being mutually coupled with.The micro-fluidic chip in this case device, its structure can also include micro-valve, the number of the micro-valve 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.

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：

This case is flowed with dual drive coupling operating mode driving liquid stream in the capillary channel of the four-way micro-fluidic chip, 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 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 dual drive coupling operating mode driving, various aids antibodies The AIDS disease-specific for the corresponding horseradish peroxidase-labeled that molecule is embedded by gold size sensitive membrane on electrode surface in each passage Antigen capture.

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.

Changed it is an advantage of the invention that installing miniature ultrasonic in its close position attaching of the terminal of the micro-fluidic chip Can device, it is launched using the miniature ultrasonic transducer units low-power, the ultrasonic wave of high-frequency band so that without coming to the surface The compatibility learned between strong hydrophobic its tube wall of micro-fluidic chip internal pipeline and the test object aqueous solution of modification significantly increases Plus, this is test liquid stream by there is provided a realistic possibility；Meanwhile, using dimethyl silicone polymer substrate its to ultrasound The strong absorbability of ripple, in shorter distance, it is, from the terminal to only several centimeters the sample introduction end In the very short distance of yardstick, reach the rapid decrement of ultrasonic intensity, thereby cause institute at the two ends of the micro-fluidic chip The difference of interfacial tension is stated, the difference of the interfacial tension between the two ends can cause a kind of driving force, and this kind is poor because of interfacial tension Its function of driving force is to drive test liquid stream in strong hydrophobic capillary channel originally to the terminal side caused by different To flowing；And the simultaneous Micropump in structure, its function is, leads in the sample solution and the micro-fluidic chip inside it Interfacial tension between the inwall in road is reduced by the ul-trasonic irradiation, under the increased precondition of alternate compatibility, with the Micropump The two ends that are induced come the ultrasonic wave of mechanicalness pumping strength between interfacial tension difference its driving force for being brought Support mutually, adjust mutually, be mutually coupled, one driving test liquid is pooled in the way of Collaboration and flows to the terminal side To the strength of flowing；The presence of the Micropump so that its ultrasonic wave emissive porwer of the miniature ultrasonic transducer units can be allowed to appropriateness Reduction, this is particularly suitable for for the situation containing ultrasonic wave sensitive composition in detection object；And due to the ultrasonic transducer and its The presence of radiated ultrasonic wave, it is possible to increase alternate compatibility, reduce interfacial tension, and provide the two ends interfacial tension difference its The special driving force brought, then, in this case, its flow resistance in the micro-channel of test liquid stream significantly drops Low, correspondingly, its running resistance of the Micropump is greatly reduced, so, and the Micropump just can be to carry out than relatively low pumping pressure For the pumping work of the sample solution, because mechanical pumping pressure is greatly reduced, therefore, in such a situation, Just be not susceptible to because sample introduction terminal tool pumping pressure it is excessive caused by the sample introduction end and its near zone the micro-channel drum Between bubble, expansion, deformation, distortion and the region substrate and cover plate the problems such as stripping etc.；This case dual drive coupling running Scheme and add for the sample fluid flow act it is handling, can allow for using ultrasonic intensity, ultrasonic frequency, Micropump pump power, Micropump pumping pressure etc. multiple indexs include flowing forward to be directed to the flow rate of the flowing, flowing action Dynamic or pause flowing or acceleration flowing etc. flowing action carries out multi-parameter and accurately manipulated；By this case dual drive coupling running side Case, is repaiied entirely without that must carry out any surface chemistry 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 silicon Absorption on its inner surface of pipeline of oxyalkyl 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 Plus can objectively reflect actual conditions；The effect of the low-power, high-frequency band ultrasonic wave, also includes facilitating antigen, resists certainly The quick of Reversible binding reaction between body 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 allowed to fit Degree reduction, then, the feature helps to protect its sensitive coating of the working electrode, is allowed to from ultrasound injury.

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.

Its presence of the ultrasonic wave damper in this case device, further reduce to its pumping pressure of Micropump and pump power according to Rely；Correspondingly, its running resistance of the Micropump is further greatly reduced, so, and the Micropump just can be with lower pumping Pressure carries out the pumping work for the sample solution, because mechanical pumping pressure is further greatly reduced, Therefore, in such a situation, just be less susceptible to occur because sample introduction terminal tool pumping pressure it is excessive caused by the sample introduction end and The problems such as stripping between the micro-channel bubbling of its near zone, expansion, deformation, distortion and the region substrate and cover plate etc.； The scheme of this case dual drive coupling running is further added for the test liquid due to its presence of the ultrasonic wave damper The handling of flowing action is flowed, wherein, the factor that can adjust includes ultrasonic intensity, ultrasonic frequency, Micropump pump power, micro- Pump pumps pressure, and, the selection and use of ultrasonic wave damper material, the selection of ultrasonic wave damper block size and use, The selection of the size of its corresponding ultrasonic wave abatement ability of ultrasonic wave damper and use etc., this kind of many adjustable factor it is same When exist, can more operation indexs, further, more it is multifactor adjustably for the flowing flow rate, stream Action includes flow forward or pause flowing or accelerates flowing etc. flowing action to carry out the accurate manipulation under more parameters.

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

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

Brief description of the drawings

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

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

Embodiment

In this case that Fig. 1 is shown embodiment, the structure of the device includes multichannel micro-fluidic chip, the micro-fluidic core The structure of piece includes the substrate 1 and cover plate 2 of installing bonded to each other together, and the substrate 1 and cover plate 2 are plate object or piece Contain the channel structure via mould pressing process or etching technics formation, phase in shape thing, that face towards the cover plate 2 of the substrate 1 The substrate 1 being mutually jointly mounted to together has been built into the micro-fluidic chip containing pipeline configuration jointly with the cover plate 2, the pipeline Locations of structures be located at the substrate 1 and the cover plate 2 juncture area bonded to each other, the two ends of the pipeline respectively with the micro-fluidic core The sample introduction end 5 of piece and terminal 6 are connected, and the sample introduction end 5 is the injection end of the micro-fluidic chip sample solution, and the terminal 6 is The terminal that sample solution flows in its chip when the actual sample introduction of the micro-fluidic chip is tested, the terminal 6 is mutually remote with the sample introduction end 5 From the distance between the terminal 6 and the sample introduction end 5 are between 3 centimetres and 10 centimetres, in the pipeline on diverse location Sequentially it is equiped with working electrode and to electrode and reference electrode, the working electrode is by conductive electrode and is attached to this and leads The gold size sensitive membrane for having embedded AIDS specific antigen on conductive electrodes is constituted, and the construction of the pipeline is in parallel construction, described It is made up of in the pipeline of parallel construction four lateral parallel connections, the quantity of the working electrode is four, four working electrodes Installation position be located at respectively in four laterals, and, in the sensitive membrane structure of its top layer of four working electrodes gold size Specific antigen be the four kinds of AIDS antigenic substances that can be specifically bound to aids antibody respectively, four kinds of antigenic substances point It is not AIDS specific antigen p24, gp41, gp120 and gp36, its material of the working electrode is gold material or heat Conducting polymer material is decomposed, sheet or thread is presented in the working electrode its pattern, emphasis is, its material of the substrate 1 is poly- Dimethyl siloxane material, its surface of substrate 1 is the surface of primary form, the surface of the primary form its be intended to refer to not have There is the surface of the primary form by any surface chemical modification or the material of any surface chemical modification, the structure of the device is also Including miniature ultrasonic transducer units 4, and, higher-order of oscillation electric signal transmission cable 3, the higher-order of oscillation electric signal transmission cable 3 one end links together with the miniature ultrasonic transducer units 4, and the miniature ultrasonic transducer units 4 are installed in the miniflow with attaching Control the position of the cover plate 2 of chip or the neighbouring terminal 6 of substrate 1；Its major function of the miniature ultrasonic transducer units 4 is In the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it reduces sample solution and the micro-fluidic chip in it Interfacial tension between the inwall of portion's passage, can be compatible, also, utilizes the sample introduction end 5 and the terminal 6 With the difference on the distance between the installation position of miniature ultrasonic transducer units 4 difference and its ultrasonic intensity experienced, Difference between its interfacial tension of sample introduction end 5 described in induced synthesis and the terminal 6 its interfacial tension, the micro-fluidic chip this two Interfacial tension difference between end 5,6 can form pressure gap between the two ends 5,6 of the micro-fluidic chip, the pressure Difference can drive sample solution to be flowed to the direction of terminal 6；Its function of the miniature ultrasonic transducer units 4 also includes being sent out with it The ultrasonic wave penetrated checks in sample contained large biological molecule its absorption on the micro-fluidic chip its inner passage inner surface, And then check swallow up effect of its body phase of the substrate 1 of the dimethyl silicone polymer material to the large biological molecule；Softness simultaneously has elasticity The substrate 1 of the dimethyl silicone polymer material its function include, with its property to the strong absorption of ultrasonic wave, carrying out ultrasonic wave It is strong to absorb, and thereby in the micro-fluidic chip, the terminal 6 arrives realization ultrasound within the limited short distance between the sample introduction end 5 The rapid decrement of intensity of wave；And, Micropump 7, the Micropump 7 is connected with the sample introduction end 5；The function of the Micropump 7 is, at this Interfacial tension between sample solution and the inwall of its inner passage of micro-fluidic chip is reduced by the ul-trasonic irradiation, alternate phase Under the increased precondition of capacitive, the two ends 5,6 induced with the ultrasonic wave are come with the mechanicalness pumping strength of the Micropump 7 Between interfacial tension difference its driving force brought support mutually, adjust mutually, be mutually coupled, with the side of Collaboration Formula pools the strength that one driving test liquid flows to the direction of terminal 6 flowing；Its thickness of the cover plate 2 and substrate 1 is situated between Between 1.0 millimeters and 5.0 millimeters；And, ultrasonic wave damper, its profile of the ultrasonic wave damper in block, tabular or It is 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, and the medial surface of each clamping limb is relative with the medial surface of another clamping limb, one of clamping The medial surface of arm is close to the sample introduction end 5 of the micro-fluidic chip, and the medial surface of another clamping limb is close to the ultrasonic wave damper, The elastic clip with its gripping strength by the sample introduction end 5 of the micro-fluidic chip and the ultrasonic wave damper it is bonded to each other clip together, The strong consumption to ultrasonic wave that the ultrasonic wave damper is brought with its material, further supporting should in the micro-fluidic chip Terminal 6 thereby further expands to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 5 Difference between its interfacial tension of big described its interfacial tension of sample introduction end 5 and the terminal 6.

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

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

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

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

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

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

Micropump 7 can be customized to specialized factory involved by legend.

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

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

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

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

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. the AIDS diagnosis micro flow control chip device that operating mode is coupled based on dual drive, the structure of the device includes multichannel Micro-fluidic chip, the structure of the micro-fluidic chip includes the substrate and cover plate of installing bonded to each other together, the substrate and cover plate It is plate object or tablet, the groove via mould pressing process or etching technics formation is contained in that face towards the cover plate of the substrate Road structure, substrate bonded to each other being installed together has been built into the micro-fluidic chip containing pipeline configuration jointly with the cover plate, The locations of structures of the pipeline is located at the substrate and cover plate juncture area bonded to each other, and the two ends of the pipeline are micro-fluidic with this respectively The sample introduction end of chip and terminal connection, the sample introduction end is the injection end of the micro-fluidic chip sample solution, and the terminal is the miniflow The terminal of sample solution flowing in its chip when the actual sample introduction of chip is tested is controlled, the terminal is located remotely from each other with the sample introduction end, the terminal With the distance between the sample introduction end between 3 centimetres and 10 centimetres, work is sequentially equiped with diverse location in the pipeline Electrode and to electrode and reference electrode, the working electrode is by conductive electrode and the bag being attached on the conductive electrode The gold size sensitive membrane for having buried AIDS specific antigen is constituted, and the construction of the pipeline is in parallel construction, the pipe in parallel construction Road is made up of four lateral parallel connections, and the quantity of the working electrode is four, the installation position difference of four working electrodes In four laterals, and, the specific antigen point in the sensitive membrane structure of its top layer gold size of four working electrodes It is not the four kinds of AIDS antigenic substances that can be specifically bound to aids antibody, four kinds of antigenic substances are that AIDS is special respectively Property antigen p24, gp41, gp120 and gp36, its material of the working electrode be gold material or thermal decomposition conducting polymer Sheet or thread is presented in material, its pattern of the working electrode, it is characterised in that its material of the substrate is dimethyl silicone polymer Material, its surface of the substrate is the surface of primary form, the surface of the primary form its be intended to refer to not pass through any surface The surface of the primary form of the material of chemical modification or any surface chemical modification, the structure of the device also includes miniature ultrasonic Transducer, 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 Wave transducer links together, the miniature ultrasonic transducer units attach be installed in the micro-fluidic chip cover plate or substrate it is neighbouring The position of the terminal；Its major function of the miniature ultrasonic transducer units is, in the actual sample introduction test of micro-fluidic chip, to utilize it The ultrasonic wave launched reduces the interfacial tension between sample solution and the inwall of its inner passage of micro-fluidic chip, can It is enough compatible, also, utilize the distance between the sample introduction end and the terminal and miniature ultrasonic transducer units installation position difference Difference on different and its ultrasonic intensity for being experienced, its interfacial tension of sample introduction end described in induced synthesis and its boundary of the terminal Interfacial tension difference between difference between the tension force of face, the micro-fluidic chip two ends can the two ends of the micro-fluidic chip it Between form pressure gap, the pressure gap can drive sample solution to the end flow；Its function of the miniature ultrasonic transducer units Also include with its ultrasonic wave launched check in sample contained large biological molecule its in its inner passage of the micro-fluidic chip Absorption on inner surface, and then check swallow up work of its body phase of the substrate of the dimethyl silicone polymer material to the large biological molecule With；It is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and include with its property to the strong absorption of ultrasonic wave Matter, is absorbed strongly to ultrasonic wave, and thereby in micro-fluidic chip terminal to the limited short distance between the sample introduction end Within realize the rapid decrement of ultrasonic intensity；And, Micropump, the Micropump is connected with the sample introduction end；The function of the Micropump is, Interfacial tension between the inwall of the sample solution with its inner passage of micro-fluidic chip is reduced by the ul-trasonic irradiation, phase Between under the increased precondition of compatibility, come with the mechanicalness pumping strength of the Micropump between the two ends that are induced the ultrasonic wave Interfacial tension difference its driving force brought support mutually, adjust mutually, be mutually coupled, converged in the way of Collaboration It is polymerized to the strength that one driving test liquid flows to the terminal direction flowing；Described its thickness of cover plate and substrate is between 1.0 millimeters Between 5.0 millimeters；And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；This surpasses Its material of sound wave damper is microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force is accompanied Two clamping limbs, the medial surface of each clamping limb is relative with the medial surface of another clamping limb, the medial surface of one of clamping limb Be close to the sample introduction end of the micro-fluidic chip, the medial surface of another clamping limb is close to the ultrasonic wave damper, the elastic clip with Its gripping strength by the sample introduction end of the micro-fluidic chip and the ultrasonic wave damper it is bonded to each other clip together, the ultrasonic wave abatement The strong consumption to ultrasonic wave that device is brought with its material, is further supported in micro-fluidic chip terminal to the sample introduction The rapid decrement of ultrasonic intensity is realized within limited short distance between end, and thereby further expands described its boundary of sample introduction end Difference between face tension force and the terminal its interfacial tension.

2. the AIDS diagnosis according to claim 1 micro flow control chip device that operating mode is coupled based on dual drive, its It is characterised by, it is capillary channel that the pipeline, which includes the lateral,.

3. the AIDS diagnosis according to claim 1 micro flow control chip device that operating mode is coupled based on dual drive, its Be characterised by, the thermal decomposition conducting polymer be by polyimides or polyacrylonitrile be heat-treated through anoxybiotic after the electric conductivity material that is formed Material.

4. the AIDS diagnosis according to claim 1 micro flow control chip device that operating mode is coupled based on dual drive, its Be characterised by, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, work electricity The length of pole is between 1 micron to 15000 microns.

5. the AIDS diagnosis according to claim 1 micro flow control chip device that operating mode is coupled based on dual drive, its It is characterised by, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.

6. the AIDS diagnosis according to claim 1 micro flow control chip device that operating mode is coupled based on dual drive, its It is characterised by, its material of the cover plate in structure is dimethyl silicone polymer material.

7. the AIDS diagnosis according to claim 1 micro flow control chip device that operating mode is coupled based on dual drive, its It is characterised by, the Micropump is miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.

8. the AIDS diagnosis according to claim 1 micro flow control chip device that operating mode is coupled based on dual drive, its It is characterised by, the microcellular rubber is micropore silicon rubber or micropore fluorubber.

9. the AIDS diagnosis according to claim 1 micro flow control chip device that operating mode is coupled based on dual drive, its It is characterised by, the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission electricity Its other end of cable is connected with the higher-order of oscillation electric signal generator.

10. the AIDS diagnosis according to claim 1 micro flow control chip device that operating mode is coupled based on dual drive, its It is characterised by, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 2 milliwatts and 2000 milliwatts, and this is micro- The frequency of its ultrasonic wave operationally launched of type ultrasonic transducer is between 100KHz and 12MHz.