CN105879932A - Multi-channel micro-fluidic chip device for simultaneously detecting various kinds of subtype swine flu - Google Patents

Abstract

The invention relates to a multi-channel micro-fluidic chip device for simultaneously detecting various kinds of subtype swine flu and belongs to the field of analytical testing. When polydimethylsiloxane, namely PDMS, which is cheap and extremely easy to process is used for making a substrate of a micro-fluidic chip for diagnosing subtype swine flu, many obstacles exist; the surface of a PDMS material is strongly hydrophobic, while the effect of specific surface modification cannot last. According to the scheme, the multi-channel micro-fluidic chip device aims at solving the series of related problems, and is characterized in that PDMS with an original surface is selected as a substrate, a miniature ultrasonic transducer is attached to and arranged at the position close to the sample liquid flow terminal of a micro-fluidic chip, and interfacial tension is reduced with ultrasonic waves; meanwhile, the strong absorption capability of PDMS to ultrasonic waves is utilized for quickly reducing the intensity of the ultrasonic waves gradually in a short distance, an interfacial tension difference is formed at the two ends of the chip accordingly, a pressure difference is formed between the two ends, and the sample liquid flow is driven to flow towards the terminal along capillary channels by the pressure difference.

Description

Detect the multichannel micro-fluidic chip device of multiple hypotype swine flue simultaneously

Technical field

The present invention relates to a kind of multichannel micro-fluidic chip device simultaneously detecting multiple hypotype swine flue, belong to Analyze field tests.

Background technology

Multichannel micro-fluidic hypotype swine flue diagnostic techniques background, may refer to CN 201110311127.1 Deng application for a patent for invention case.

Only for itself overall general picture of microflow control technique, may refer to famous micro-fluidic expert Lin Ping Cheng The monograph " diagram Microfluid based Lab on a chip " that Mr. goes out not long ago, this monograph is gone out by Science Press Version, this monograph to past of microflow control technique, now, and, vision of the future etc. aspect, suffer from detail Most, to be deep into detail long discussion.

So, the Important Problems that this case to be had a talk is paid close attention to.

The basic framework of micro-fluidic chip, including being etched with the substrate of small fluid course and being fitted in therewith Cover plate together, the small fluid course on described substrate, before fit on cover plate, apparent on see and be exactly Some micro-channel, after waiting until to cover cover plate thereon, just the real Guan Bi described small liquid stream of formation leads to Road, the conduit inner surface of this micro-channel constitutes described together with the part cover plate that surround this micro-channel Small fluid course；So, it is clear that assemble this small fluid course after completing, its inner surface The major part of area is the inner surface area of that micro-channel, in other words, and the shape of this micro-channel inner surface State or character substantially determine integrality or the character of this small fluid course；Therefore saying, this builds Inner surface state or the inner surface character of the micro-channel on substrate are key factors；In principle, any The material of its solid forms be can keep or substantially keep, substrate and cover plate can be used to make, such as, The material that can act as substrate and cover plate can be monocrystalline silicon piece, piezoid, sheet glass, high polymer the most poly-two Methylsiloxane, polymethyl methacrylate, Merlon etc.；Certainly, the selection of substrate and cover plate Selection can be identical, it is also possible to differs；From material consumption, manufacture difficulty and application popularization prospect etc. From the point of view of aspect, between these materials, there is the selection of the least difference, especially that substrate, affect bigger.

In various substrates make material, polydimethylsiloxane, i.e. PDMS, the easiest Molding, makes micro-channel extremely simple on such substrate, and this lower cost for material, with this poly-two Methylsiloxane material makes substrate, suppresses or etch micro-channel thereon, and with glass or polypropylene or its The cover plate that the cheap materials such as its plastic sheet make matches, and is a kind of more satisfactory selection seemingly；Certainly, Patch material can also select to use cheap polydimethyl siloxane material: so, and this substrate selection is The scheme of polydimethyl siloxane material, material is extremely cheap, makes extremely simple, seem should also be as being extremely easy to general And, promote.

But, thing is really not so simply.

One, this polydimethyl siloxane material, the material that i.e. abbreviation letter PDMS is referred to, its Body is the most hydrophobic a kind of material, builds micro-channel, if do not carried out for this microflute on this material The modified operation on surface, road, then, after entirety has been assembled, after i.e. covering cover plate, because of the institute in structure State its inner surface of micro-channel and occupy the inner surface of most fluid course, then, this PDMS micro-channel Its strong hydrophobic property of inner surface, is deciding factor, and it can make to be similar to the polar liquid of aqueous solution Fine liquid stream by becoming the most difficult, its flow resistance is big, and the most general Micropump is all difficult to promote, Certainly, if cover plate also selects to use this PDMS material, then, problem is substantially identical, similar； Therefore, among prior art, it is modified repairing particular for the micro-channel inner surface on this PDMS material Decorations, are necessary operations；So, this operates pretty troublesome for the modification of PDMS micro-channel inner surface？ That is not this problem, constitutes serious technical puzzlement, is another problem: this PDMS material The PDMS polymer molecule of its body of substrate inside mutually has the characteristic automatically diffusing to the surface, migrating, this The substrate body characteristic that internal PDMS polymer molecule automatically diffuses to the surface, migrates mutually, will make through table When state after the modification of that its inner surface of micro-channel of face modifying and decorating can not maintain sufficiently long Between, holding time of its inner surface state of the micro-channel after that is surface-modified has substantially been only sufficient to experiment The time of chamber interior test experiments needs；In other words, this PDMS modified through surface modification or surface Micro-channel inner surface, after its modification or say the apparent condition formed after modification can not be lasting, but Automatically tend to soon or say the apparent condition become again before surface modification, in relatively short period of time, returning to that The most hydrophobic apparent condition kind originally, then, just think, such micro-fluidic chip can make in a large number, Mass storage, being widely popularized, answer is clearly, that is, it is impossible to.On this PDMS material Micro-channel, does not do if surface modifies, and is similar to the fine liquid stream of polar solvent of aqueous solution and cannot pump and pass through, Chip the most just cannot use；And if done surface modification, cannot persistently keep again its modify after state, The most equally cannot popularization and application.

So, how to accomplish to utilize cheap PDMS material to make substrate, and institute can be released State micro-channel inner surface decorating state cannot persistently, chip cannot make in a large number, in a large number deposit so that extensively push away The most such a puzzlement making the numerous professional in this area be entangled with for a long time, it is simply that its obvious technology The highly difficult problem that obstacle can not be despised.

Having there are a lot of days in this highly difficult problem, up to now, is not yet properly settled.

Its two, the PDMS material of non-surface modification, above it is stated that, its surface is the most hydrophobic, this Plant the most hydrophobic material surface and also have another problem, that is, the most hydrophobic this PDMS Biomacromolecule can be adsorbed in surface, and, these adsorbed biomacromolecules also can be further at PDMS Depression further on surface, gradually falls into gradually deep, until within the heavy body phase being trapped in PDMS substrate, its Real, this process, partly it is also due to PDMS material body phase interior polymeric thing molecule and has to surface expansion Dissipate, travel motion is caused；This situation, it is also possible to explain from another angle, i.e. constant Ground is internal to its diffusion into the surface, those polymer molecules of migration mutually by PDMS body, the result of its motion, Within being the body phase that little by little those have been involved in by the biomacromolecule of surface adsorption PDMS substrate, letter Singly saying, these adsorbed biomacromolecules are swallowed up mutually by PDMS substrate body exactly；So, this PDMS substrate body swallows up the phenomenon of biomacromolecule mutually, its impact caused, and necessarily causes relating to raw The severe deviations of all kinds of test data of experiment of thing macromole.

As it has been described above, the problem of PDMS substrate is, its not only surface adsorption biomacromolecule, and swallow up Biomacromolecule, so, its disappearance of biomacromolecule as experiment test object will not be because of surface Saturated absorption and stop, but, be constantly adsorbed, the most constantly swallowed up.

About PDMS substrate in related experiment test process its body the most constantly swallow up test associated biomolecule divide greatly The phenomenon of son, another kind of explanation is to say, PDMS body mutually in there is substantial amounts of Minute pores, associated biomolecule is big Molecule is by after surface adsorption, and depression enters these Minute pores, and then is swallowed up；But, this case is invented People thinks, those can allow that the air molecule of miniature scale clamp-ons described Minute pores therebetween, is not equal to Saying that they also can directly allow that the biomacromolecule of relatively large yardstick enters, both difference on yardstick are huge, Must not make sweeping generalizations.Bypass explanation, in any case, analyze the biomacromolecule quilt of object as dependence test PDMS substrate micro-channel inner surface adsorbs, and then is constantly swallowed up by PDMS substrate body phase, and this is known The phenomenon of objective reality.

In order to stop the effect of swallowing up relative to biomacromolecule of this PDMS substrate body, can be from containment The absorption of biomacromolecule is addressed by PDMS surface, and way is aiming at this PDMS material surface It is chemically modified modification, from the point of view of during with PDMS as substrate material, it is simply that to described microflute The surface of road part is chemically modified modification, through the described micro-channel inner surface that chemical modification is modified, energy Enough contain its absorption to biomacromolecule, and then avoid biomacromolecule to be swallowed up by PDMS substrate body phase； But, or that old problem, that is, the table after chemical modification modification on PDMS material surface Surface state cannot persistently keep, the internal mutually polymer molecule of this PDMS substrate body its automatically diffuse to the surface, The process migrated, can become again that through the micro-channel inner surface state that surface chemical modification is modified soon The most hydrophobic and the state of strong adsorption biomacromolecule originally, in other words, no matter this field is professional How personnel turn from side to side, and its micro-channel inner surface of this PDMS substrate is the most rapidly to strong hydrophobic surface shape State develops.

So, it is the best how can either to obtain that PDMS material price is the cheapest, substrate makes Place, can reach again long-term this PDMS substrate micro-channel inner surface absorption process to biomacromolecule of containment, And then stoping the effect of swallowing up of PDMS substrate body Relative biological macromole so that related chip manufactured goods can Maintain a shelf-life the most long, rational, it is simply that a difficult problem the most thorny.This difficult problem is such as The same with another difficult problem addressed above, make the numerous professional in this area be entangled with for a long time, perplex equally, This difficult problem is the highly difficult problem that its obvious technology barrier can not be despised equally.This difficult problem is the most There are a lot of days, up to now, the most not yet properly settled.

Summary of the invention

The technical problem to be solved is to provide a package solution, solves totally Two difficult problems certainly addressed above, and, this solution is applied to hypotype swine flue diagnosis multichannel Micro-fluidic chip field, forms a kind of novel hypotype swine flue diagnosis multichannel micro-fluidic device.

The present invention solves described technical problem by following scheme, and the device that the program provides is that one is examined simultaneously Surveying the multichannel micro-fluidic chip device of multiple hypotype swine flue, the structure of this micro fluidic device includes multichannel Micro-fluidic chip, the structure of this micro-fluidic chip includes bonded to each other being installed in substrate together and cover plate, institute Stating substrate and cover plate is plate object or tablet, that face towards this cover plate of this substrate is contained via mould The channel structure that pressure technique or etching technics are formed, this substrate is possibly together with being connected with this channel structure and piercing The window structure formed via mould pressing process, etching technics or simple drilling technology of this substrate, bonded to each other This substrate being installed together and this cover plate have been built into jointly containing pipeline configuration and the liquid pool that is attached thereto The micro-fluidic chip of structure, the locations of structures of this pipeline is positioned at the boundary zone that this substrate is bonded to each other with this cover plate Territory, its side of this window is blocked by this cover plate and opposite side is open, and the locations of structures of this window is exactly described liquid The locations of structures in pond, the quantity of described liquid pool is three, and it is micro-that two its locations of structures of liquid pool therein are positioned at this The sample introduction end of fluidic chip, remaining its locations of structures of liquid pool is positioned at the actual sample introduction of this micro-fluidic chip and surveys The terminal of liquid flowing in its chip during examination, this terminal is located remotely from each other with this sample introduction end, one end warp of this pipeline By be similarly positioned in the manifold shape turnout of this interface zone bonded to each other respectively with these two liquid being positioned at sample introduction end Pond UNICOM, this remaining liquid pool of the other end of this pipeline and the described terminal being positioned at this micro-fluidic chip UNICOM, and, the working electrode that is sequentially respectively installed in this pipeline on diverse location and to electrode and Reference electrode, described working electrode is by conductive electrode and the embedding that is attached on this conductive electrode Asia The gold size sensitive membrane of type swine flue specific antigen is constituted, and the structure of this pipeline is parallel construction, described in also The pipeline of connection structure is made up of three lateral parallel connections, and the quantity of described working electrode is three, these three The installation position of working electrode lays respectively in described three laterals, and, these three working electrodes its Specific antigen in the gold size sensitive membrane structure of top layer respectively can be specific binding to hypotype swine flue antibody Three kinds of hypotype swine flue antigenic substances, these three kinds of antigenic substances are hypotype swine flue specific antigen H respectively₁N₁、 H₃N₂And H₁N₂, its material of described working electrode is gold material or thermal decomposition conducting polymer material, described work Make its pattern of electrode and present lamellar or thread, it is important that, its material of this substrate is polydimethylsiloxane material, Its surface of this substrate is the surface of primary form, the surface of this primary form its be intended to refer to not through appointing The surface of the primary form of this material of what surface chemical modification or any surface chemical modification, this micro-fluidic dress The structure put also includes miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, this high frequency One end of vibration electric signal transmission cable links together with this miniature ultrasonic transducer units, this miniature ultrasonic Transducer is installed in the cover plate of this micro-fluidic chip or the position of the neighbouring described terminal of substrate with attaching；This is micro- Its major function of type ultrasonic transducer is when the actual sample introduction of micro-fluidic chip is tested, and utilizes it to be launched Ultrasound wave reduces the interfacial tension between the inwall of sample solution and described pipeline so that it is can be compatible, and And, utilize the distance between described sample introduction end and described terminal and this miniature ultrasonic transducer units installation position Difference in difference and its ultrasonic intensity experienced, its interfacial tension of sample introduction end described in induced synthesis And the difference between its interfacial tension of described terminal, the interfacial tension difference between these two ends of this micro-fluidic chip Can between these two ends of this micro-fluidic chip formed pressure gap, this pressure gap can drive sample solution to Described end flow；Its function of this miniature ultrasonic transducer units also includes checking examination with its ultrasound wave launched Its absorption on described inner surface of pipeline of biomacromolecule contained in sample, and then check this poly dimethyl Its body of the substrate of siloxanes material is relative to the effect of swallowing up of this biomacromolecule；Described polydimethylsiloxane material Its function of the substrate of matter includes and cover plate and working electrode and that electrode and reference electrode are together built this is micro-fluidic Chip, soft and this polydimethylsiloxane material of having elasticity its function of substrate also includes with it ultrasonic The character that ripple absorbs strongly, absorbs strongly to ultrasound wave, and thereby arrives in this terminal of this micro-fluidic chip The rapid decrement of ultrasonic intensity is realized within limited short distance between this sample introduction end.

Described gold size sensitive membrane is by the most mixed with hypotype swine flue specific antibody solution for chitosan gold size solution Close uniformly, with point sample instrument point sample or coat specified structure position, and make its drying and forming-film form.Described gold Hypotype swine flue specific antibody in glue sensitive membrane is horseradish peroxidase or glucose oxidase mark The hypotype swine flue antibody of note, described gold size sensitive membrane has been included as fixing above-mentioned each hypotype swine flue specificity Antibody and introduce complementary medium therein, described complementary medium such as chitosan, cellulose acetate, bright Glue is therein a kind of or their mixture.

Described pipeline in described microfluidic chip structure and described lateral and described manifold shape trouble Road, its internal diameter size may each be arbitrarily selected size, but, for as far as possible less with liquid sample to be measured and Reduce the consideration of the aspects such as reagent loss, described pipeline and described lateral and described manifold shape turnout The passage of capillary level, the passage of described capillary level is the most all selected to imply that on its internal diameter and ordinary meaning The passage that the internal diameter of capillary tube is suitable.The shape of cross section of described its inner passage of capillary tube can be arbitrary Shape, described shape of cross section is the most circular, oval, square, rectangle, bar shaped, naturally it is also possible to be It is linear that arbitrary existence bends, and, the interior shape of described capillary tube is along with the extension of pipeline, different The shape of cross section at position can also allow to be different shapes.Only for capillary tube one word, its technology contains Justice is known.

Relate in structure is minute sized electrode to electrode and reference electrode, its electrode shape To be arbitrarily selected shape, described arbitrarily selected shape such as square piece shape, rectangular patch, strip or Round sheet etc..Described is known to itself the art-recognized meanings of vocabulary of electrode and described reference electrode 's.

Relating to several liquid pools in this case microfluidic chip structure, described liquid pool is the pond for transitional liquid storage Shape or scrotiform structure, its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, institute State cavity shape such as cylindrical empty cavity-like, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc. Deng.The size of described liquid pool can be arbitrarily selected size, but, in order to use liquid to be measured less as far as possible Sample and reduction reagent loss, described liquid pool is preferably capable of the hypomegetic liquid pool mated with capillary tube.

Only with regard to itself art-recognized meanings of ultrasonic transducer one word for the professional in ultrasonic technology field For, it is known.

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

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

Only with regard to naked PDMS substrate itself micro-channel mold or lithographic technique for, be open-and-shut known Technology；Similarly, the technology of hole-opening known simple technique especially on naked PDMS substrate.This case This is not launched superfluous words.

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

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

Itself technology of involved higher-order of oscillation electric signal generator, for the professional people in ultrasonic technology field For Yuan, it is simple and known；Described higher-order of oscillation electric signal generator can be special to ultrasonic instrument Industry producer customizes.

The preferred scope of its specified ultrasonic emitting power of this miniature ultrasonic transducer units be between 2 milliwatts with Between 2000 milliwatts；The frequency of its ultrasound wave operationally launched of this miniature ultrasonic transducer units preferred Scope is between 100KHz and 12MHz.

This case device can further include some adnexaes certainly, described adnexa such as multiple tracks electrochemical operation Standing etc., the art-recognized meanings of described multiple tracks electrochemical workstation is known.In this case microfluidic chip structure Each working electrode of relating to and to electrode and reference electrode etc., can be respectively via corresponding special string Line couples with the corresponding interface of described multiple tracks electrochemical workstation.Described special getting lines crossed is being used to Jiang Gesuo State the private cable that each the corresponding interface of electrode and described multiple tracks electrochemical workstation carries out being coupled to each other.This case Described micro-fluidic chip in device, its structure can also include that micro-valve, the quantity of described micro-valve do not limit, root According to being actually needed, any need position to be mounted that described micro-valve can be installed in this microfluidic chip structure； This micro-valve one word is for the professional of micro fluidic chip technical field, and the art-recognized meanings of itself is public Know；This micro-valve itself manufacturing technology and use technology be also known；This optional structure of micro-valve Part.

The diameter of described working electrode can allow the suitable diameter being easily installed use being arbitrarily set, It is however recommended to or say preferred its scope of described diameter between 0.1 micron to 2000 micron；Described The length of working electrode can allow the length being easily installed use being arbitrarily set, it is however recommended to or Saying preferred its scope of described length is between 1 micron to 15000 micron.

It is installed in described working electrode surface layer by spraying or point sample instrument point sample or the coating of other appropriate process Described gold size sensitive membrane, its thicknesses of layers can allow the sample measuring liquid treated being arbitrarily set that electrically letter occurs The thickness of number response, it is however recommended to thickness in other words conj.or perhaps preferably thickness be between 10 nanometers and 200 Between nanometer.

Described cover plate in chip structure, its material can allow to be any electrical insulating property material, such as: Polypropylene, glass, polymethyl methacrylate, polydimethylsiloxane, etc., in order to make less chi Very little micro-fluidic chip, such as makes the micro-fluidic core of the super-small of length only 2.0 centimetres to 3.0 centimetres Sheet, and in the distance that this is extremely short, realize the extremely fast decay to ultrasound wave, it may be preferred to polydimethylsiloxanes Alkane is used as cover plate.Certainly, large-sized micro-fluidic chip selects use polydimethylsiloxane to make For described cover plate, also it is that this case technical scheme is allowed.

Be positioned at this micro-fluidic chip this sample introduction end these two liquid pools its be positioned at this terminal of this micro-fluidic chip This remaining liquid pool between air line distance can be arbitrarily selected suitable distance as required, But, the preferred value of this distance is between 3 centimetres and 7 centimetres.

Described cover plate and its thickness of substrate can allow the thickness being easy to assembling being arbitrarily set, it is recommended that thickness Spending or saying preferred thickness is between 1.0 millimeters and 5.0 millimeters.Less thickness is conducive to saving material Material.

The using method of this case micro-fluidic chip:

Propose first based on this case and this first public novel liquid stream driving principle, this case micro-fluidic chip its Among application running, this novel liquid stream driving method determines completely without involving any additional Micropump.

This interfacial tension formed between these two ends of this micro-fluidic chip that this case is caused with described ultrasound wave Difference, drives liquid stream to flow in the capillary channel of this triple channel micro-fluidic chip, utilizes multichannel electrification Learn analytical tool respectively three kinds of hypotype swine flue diagnostic antigens to be detected.

Corresponding three kinds of hypotype swine flue antibody are detected, and by three kinds of hypotypes with three kinds of hypotype swine flue antigens Swine flue antibody detects corresponding three kinds of hypotype swine flue antigens, similarly, can diagnose corresponding Asia Type swine flue；The principle of its foundation is, necessarily antigen, antibody deposit in hypotype swine flue patient, And mutual Reversible binding, form reversible conjugate, therefore, detect antibody with antigen and thereby diagnose phase The hypotype swine flue answered, goes detect antigen and diagnose corresponding hypotype swine flue with antibody, can reach Diagnostic purpose.Certainly, its corresponding electrode sensitive decorative layer of different means technically and differs.

The concrete detection of this case micro-fluidic chip uses step as follows:

1, in micro-pipeline, blood serum sample liquid, under described ultrasound wave drives, various hypotype swine flue are added Antibody molecule is by the corresponding horseradish peroxidase-labeled of gold size sensitive membrane embedding on electrode surface in each passage Hypotype swine flue specific antigen capture.

2, the hypotype swine flue specific antigen of horseradish peroxidase-labeled and the hypotype pig in blood serum sample Influenza antibodies forms immune complex.

3, use multi-channel electrochemical analyzer, add the electron mediators such as catechol, use Amperometric Detect the curent change that above-mentioned reaction causes, be derived from kind and the content of various analyte.

4, result is comprehensively analyzed, hypotype swine flue antibody is carried out comprehensive diagnos.

It is an advantage of the invention that its close position of described terminal at described micro-fluidic chip is installed micro-with attaching Type ultrasonic transducer, utilize its low-power launched of this miniature ultrasonic transducer units, high-frequency band super Sound wave so that without surface chemical modification this most hydrophobic its tube wall of micro-fluidic chip internal pipeline with Test object water solution between the compatibility be significantly increased, this for sample liquid stream by providing a reality Probability；Meanwhile, utilize its strong absorbability to ultrasound wave of polydimethylsiloxane substrate, comparing In short distance, it is, the only several centimeters yardstick from described terminal to described sample introduction end is the shortest Apart from interior, reaching the rapid decrement of ultrasonic intensity, thereby institute is caused at the described two ends at this micro-fluidic chip State the difference of interfacial tension, and then, utilize the interfacial tension between these two ends difference its formed this two Pressure gap between end, drive sample liquid stream in the capillary channel that such a is originally the most hydrophobic to Flow in described terminal direction.By this case liquid stream drive scheme, entirely without must be to this polydimethylsiloxane material The substrate of matter and internal pipeline thereof carry out any surface chemical modification or chemical modification, have altogether dispensed with this table Face chemical modification or the laborious procedures of chemical modification；And altogether dispense with traditional Micropump etc Equipment；On the other hand, the ultrasound wave of this low-power, high-frequency band, additionally it is possible to the biology in containment sample is big Molecule absorption on this literalness naked its inner surface of pipeline of polydimethylsiloxane substrate, and then containment The effect of swallowing up of this polydimethylsiloxane substrate the most described biomacromolecule of its body；Described antigen, antibody And the Reversible binding thing of antigen and antibody is the most all belonging to the type of described biomacromolecule；Due to institute Adsorption and the described effect of swallowing up stated are contained effectively, and therefore, dependence test result will more Practical situation can be reflected objectively；This low-power, the effect of high-frequency band ultrasound wave, the most also include promoting Become between antigen, antibody Reversible binding reaction quickly reach, this make dependence test operation can with than Speed completes faster.

Due to be made without the surface chemical modification for this polydimethylsiloxane its relevant surfaces of substrate or Chemical modification operates, and therefore, this surface chemical modification layer or chemically modified layer not need to exist, So, its body phase interior polymeric thing molecule of this polydimethylsiloxane substrate the most automatically diffuses to the surface, moves Move its damaging influence to described surface chemical modification layer or chemically modified layer caused not exist ?.

The technical scheme of this case dissolved totally address above with polydimethylsiloxane substrate its application Relevant a series of technical barriers.Based on this case scheme, the polydimethyl siloxane material that this kind is the most cheap The most likely prepare at micro-fluidic chip, produce, application etc. field plays bigger effect.

Accompanying drawing explanation

Fig. 1 is the schematic diagram of this micro fluidic device embodiment chip part of this case structure, it is shown that should Chip internal pipeline under the depression angle of example structure and each electrode and the configuration of each relevant liquid pool, this figure In do not depict described miniature ultrasonic transducer units and other described adnexa.

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

In figure, 1,2,8 is the liquid pool that three installation positions are different respectively, and 3 is manifold shape turnout, 4,9, 12 are installation position difference but three laterals forming UNICOM in parallel structure parallel with one another respectively, and 5 is dress Specific antigenic substance in its top layer gold size sensitive membrane structure being located in lateral 4 is hypotype swine flue Specific antigen H₁N₁Working electrode, 10 is its top layer gold size sensitive membrane knot being installed in lateral 9 Specific antigenic substance in structure is hypotype swine flue specific antigen H₃N₂Working electrode, 11 is to be installed in The specific antigenic substance in its top layer gold size sensitive membrane structure in lateral 12 is that hypotype swine flue is special Specific Antigen H₁N₂Working electrode, 6 is to electrode, and 7 is reference electrode, and 13 is polydimethylsiloxane The substrate of material, 14 is cover plate, and 15 is higher-order of oscillation electric signal transmission cable, and 16 is that miniature ultrasonic changes Energy device, 17 is the described sample introduction end of this micro-fluidic chip, and 18 is the described terminal of this micro-fluidic chip；Figure Arrow in example indicate this micro-fluidic chip its when actual motion, driven by pressure at two ends difference, its examination The flow direction of sample liquid stream.

Detailed description of the invention

In this embodiment of this case that Fig. 1 and Fig. 2 is shown, the structure of this micro fluidic device includes multichannel Micro-fluidic chip, the structure of this micro-fluidic chip includes bonded to each other being installed in substrate 13 together and cover plate 14, described substrate 13 and cover plate 14 are plate object or tablet, this substrate 13 towards this cover plate 14 That face contain the channel structure formed via mould pressing process or etching technics, this substrate 13 possibly together with this Channel structure be connected and pierce this substrate 13 via mould pressing process, etching technics or simple drilling technology shape The window structure become, this substrate 13 being installed together bonded to each other has jointly been built into this cover plate 14 and has contained Having pipeline configuration and the micro-fluidic chip of liquid pool structure being attached thereto, the locations of structures of this pipeline is positioned at this The interface zone that substrate 13 is bonded to each other with this cover plate 14, its side of this window is blocked by this cover plate 14 and another Side is open, and the locations of structures of this window is exactly the locations of structures of described liquid pool, and the quantity of described liquid pool is three Individual, these three liquid pools are liquid pool 1, liquid pool 2, liquid pool 8 respectively, two liquid pools i.e. liquid pool 1 and liquid therein Its locations of structures of pond 2 is positioned at the sample introduction end of this micro-fluidic chip, a remaining liquid pool i.e. its structure of liquid pool 8 The terminal 18 of its chip liquid flowing, this terminal 18 when position is positioned at the test of this micro-fluidic chip actual sample introduction Being located remotely from each other with this sample introduction end 17, one end of this pipeline is via being similarly positioned in this interface zone bonded to each other Manifold shape turnout 3 respectively with this two liquid pools i.e. liquid pool 1 and liquid pool 2 UNICOM, this pipe being positioned at sample introduction end 17 This remaining i.e. liquid pool 8 of a liquid pool of the other end in road and the described terminal 18 being positioned at this micro-fluidic chip UNICOM, and, the working electrode that is sequentially respectively installed in this pipeline on diverse location and to electrode and Reference electrode, described working electrode is by conductive electrode and the embedding that is attached on this conductive electrode Asia The gold size sensitive membrane of type swine flue specific antigen is constituted, and the structure of this pipeline is parallel construction, described in also The pipeline of connection structure is made up of three lateral parallel connections, and the quantity of described working electrode is three, these three The installation position of working electrode lays respectively in described three laterals, and, these three working electrodes its Specific antigen in the gold size sensitive membrane structure of top layer respectively can be specific binding to hypotype swine flue antibody Three kinds of hypotype swine flue antigenic substances, these three kinds of antigenic substances are hypotype swine flue specific antigen H respectively₁N₁、 H₃N₂And H₁N₂, from the point of view of concrete expansion, 5 is its top layer gold size sensitive membrane structure being installed in lateral 4 In specific antigenic substance be hypotype swine flue specific antigen H₁N₁Working electrode, 10 is to be installed in point The specific antigenic substance in its top layer gold size sensitive membrane structure in branch pipe(tube) 9 is hypotype swine flue specificity Antigen H₃N₂Working electrode, 11 is in its top layer gold size sensitive membrane structure being installed in lateral 12 Specific antigenic substance be hypotype swine flue specific antigen H₁N₂Working electrode, described working electrode its Material is gold material or thermal decomposition conducting polymer material, and its pattern of described working electrode presents lamellar or silk Shape, it is important that, this its material of substrate 13 is polydimethylsiloxane material, and this its surface of substrate 13 is former The surface of raw form, the surface of this primary form its be intended to refer to not through any surface chemical modification or The surface of the primary form of this material of any surface chemical modification, the structure of this micro fluidic device also includes micro- Type ultrasonic transducer 16, and, higher-order of oscillation electric signal transmission cable 15, this higher-order of oscillation electric signal One end of transmission cable 15 links together with this miniature ultrasonic transducer units 16, this miniature ultrasonic transducing Device 16 is installed in the cover plate 14 of this micro-fluidic chip or the position of the neighbouring described terminal 18 of substrate 13 with attaching Put；This its major function of miniature ultrasonic transducer units 16 is when the actual sample introduction of micro-fluidic chip is tested, profit The interfacial tension between the inwall of sample solution and described pipeline is reduced with its ultrasound wave launched so that it is Can be compatible, and, utilize described sample introduction end 17 and described terminal 18 and this miniature ultrasonic transducer units Distance difference between 16 installation positions and the difference on its ultrasonic intensity experienced, induced synthesis Difference between described its interfacial tension of sample introduction end 17 and its interfacial tension of described terminal 18, this micro-fluidic core Interfacial tension difference between these two ends of sheet can form pressure gap between these two ends of this micro-fluidic chip, This pressure gap can drive sample solution to flow to described terminal 18；This its merit of miniature ultrasonic transducer units 16 Can also include with its ultrasound wave launched check in sample contained biomacromolecule its in described pipeline Absorption on surface, and then its body of substrate 13 checking this polydimethylsiloxane material is big relative to this biology The effect of swallowing up of molecule；Its function of substrate 13 of described polydimethylsiloxane material include with cover plate 14 and Working electrode 5,10,11 and electrode 6 and reference electrode 7 are together built this micro-fluidic chip, softness is also Its function of substrate 13 of this polydimethylsiloxane material that tool is elastic also includes with its suction strong to ultrasound wave The character received, strongly absorbs ultrasound wave, and thereby enters to this in this terminal 18 of this micro-fluidic chip The rapid decrement of ultrasonic intensity is realized within limited short distance between sample end 17.

Arrow in legend indicate this micro-fluidic chip its when actual motion, driven by pressure at two ends difference Dynamic, the flow direction of its sample liquid stream.

Fig. 1 is depicted without miniature ultrasonic transducer units 16 and higher-order of oscillation electric signal transmission cable 15； Further, Fig. 1 and Fig. 2 is all depicted without described higher-order of oscillation electric signal generator and multiple tracks electrochemical operation The associate member such as stand.

Involved miniature ultrasonic transducer units 16 is commercially available；Can also customize to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal transmission cable 15 is commercially available；Can also be to ultrasonic transducer producer Customization.

Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；Can also be to phase shutout Family's customization.

Each working electrode in this example structure and can be respectively via respectively acting on one's own to electrode and reference electrode Cable or say get lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as adnexa or say string Line interface couples.

Capillary tube on usual expression and significance refers to hydrophilic capillary glass tube；Capillary tube involved by this case leads to Road is but the pipeline of hydrophobic capillary tube form.

Claims (10)

1. Detect the multichannel micro-fluidic chip device of multiple hypotype swine flue, the structure of this micro fluidic device the most simultaneously Including multichannel micro-fluidic chip, the structure of this micro-fluidic chip includes the substrate being installed in together bonded to each other And cover plate, described substrate and cover plate be plate object or tablet, that face towards this cover plate of this substrate Containing the channel structure formed via mould pressing process or etching technics, this substrate possibly together with this channel structure phase Connect and pierce the window structure formed via mould pressing process, etching technics or simple drilling technology of this substrate, This substrate being installed together bonded to each other and this cover plate have been built into jointly containing pipeline configuration and phase therewith The micro-fluidic chip of liquid pool structure even, it is bonded to each other with this cover plate that the locations of structures of this pipeline is positioned at this substrate Interface zone, its side of this window is blocked by this cover plate and opposite side is open, and the locations of structures of this window is just Being the locations of structures of described liquid pool, the quantity of described liquid pool is three, two its locations of structures of liquid pool therein Being positioned at the sample introduction end of this micro-fluidic chip, it is real that remaining its locations of structures of liquid pool is positioned at this micro-fluidic chip The terminal of liquid flowing in its chip during the sample introduction test of border, this terminal is located remotely from each other with this sample introduction end, this pipeline One end via be similarly positioned in the manifold shape turnout of this interface zone bonded to each other respectively be positioned at sample introduction end This Liang Ge liquid pool UNICOM, the other end of this pipeline is remaining with this of described terminal being positioned at this micro-fluidic chip One liquid pool UNICOM, and, the working electrode that is sequentially respectively installed in this pipeline on diverse location and right Electrode and reference electrode, described working electrode is by conductive electrode and is attached on this conductive electrode The gold size sensitive membrane having embedded hypotype swine flue specific antigen is constituted, and the structure of this pipeline is parallel construction, The described pipeline in parallel construction is made up of three lateral parallel connections, and the quantity of described working electrode is three, The installation position of these three working electrodes lays respectively in described three laterals, and, these three work Specific antigen in its top layer gold size sensitive membrane structure of electrode is to hypotype swine flue antibody energy specificity respectively In conjunction with three kinds of hypotype swine flue antigenic substances, these three kinds of antigenic substances be respectively hypotype swine flue specificity resist Former H₁N₁、H₃N₂And H₁N₂, its material of described working electrode is gold material or thermal decomposition conducting polymer material, Its pattern of described working electrode presents lamellar or thread, it is characterised in that its material of this substrate is poly dimethyl Siloxanes material, its surface of this substrate is the surface of primary form, the surface of this primary form its be meant to It is not through the table of primary form of this material of any surface chemical modification or any surface chemical modification Face, the structure of this micro fluidic device also includes miniature ultrasonic transducer units, and, higher-order of oscillation electric signal passes Transmission cable, one end of this higher-order of oscillation electric signal transmission cable links together with this miniature ultrasonic transducer units, This miniature ultrasonic transducer units is installed in the cover plate of this micro-fluidic chip or the neighbouring described terminal of substrate with attaching Position；Its major function of this miniature ultrasonic transducer units is when the actual sample introduction of micro-fluidic chip is tested, profit The interfacial tension between the inwall of sample solution and described pipeline is reduced with its ultrasound wave launched so that it is Can be compatible, and, utilize described sample introduction end and described terminal to install position with this miniature ultrasonic transducer units Distance difference between putting and the difference on its ultrasonic intensity experienced, sample introduction described in induced synthesis Hold the difference between its interfacial tension and its interfacial tension of described terminal, between these two ends of this micro-fluidic chip Interfacial tension difference can form pressure gap between these two ends of this micro-fluidic chip, and this pressure gap can drive Dynamic sample solution is to described end flow；Its function of this miniature ultrasonic transducer units also includes being launched with it Ultrasound wave checks its absorption on described inner surface of pipeline of biomacromolecule contained in sample, and then holds back Only its body of substrate of this polydimethylsiloxane material is relative to the effect of swallowing up of this biomacromolecule；Described poly-two Its function of the substrate of methylsiloxane material includes and cover plate and working electrode and to electrode and reference electrode together Building this micro-fluidic chip, soft and this polydimethylsiloxane material of having elasticity its function of substrate is also wrapped Include with the character of its absorption strong to ultrasound wave, ultrasound wave is absorbed strongly, and thereby micro-fluidic at this This terminal of chip is to the rapid decrement realizing ultrasonic intensity within the limited short distance between this sample introduction end.
2. The multichannel micro-fluidic chip dress simultaneously detecting multiple hypotype swine flue the most according to claim 1 Put, it is characterised in that described pipeline and described lateral and described manifold shape turnout are capillary tube Passage.
3. The multichannel micro-fluidic chip dress simultaneously detecting multiple hypotype swine flue the most according to claim 1 Put, it is characterised in that described thermal decomposition conducting polymer is through anoxybiotic heat by polyimides or polyacrylonitrile The conductive material formed after reason.
4. The multichannel micro-fluidic chip dress simultaneously detecting multiple hypotype swine flue the most according to claim 1 Put, it is characterised in that the width of described working electrode or diameter between 0.1 micron to 2000 micron, And, the length of described working electrode is between 1 micron to 15000 micron.
5. The multichannel micro-fluidic chip dress simultaneously detecting multiple hypotype swine flue the most according to claim 1 Put, it is characterised in that the thickness of described gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. The multichannel micro-fluidic chip dress simultaneously detecting multiple hypotype swine flue the most according to claim 1 Put, it is characterised in that its material of described cover plate in structure is polydimethylsiloxane material.
7. The multichannel micro-fluidic chip dress simultaneously detecting multiple hypotype swine flue the most according to claim 1 Put, it is characterised in that be positioned at this micro-fluidic chip this sample introduction end these two liquid pools its be positioned at this miniflow Air line distance between this remaining liquid pool of control this terminal of chip is between 3 centimetres and 7 centimetres.
8. The multichannel micro-fluidic chip dress simultaneously detecting multiple hypotype swine flue the most according to claim 1 Put, it is characterised in that described cover plate in structure and its thickness of substrate all between 1.0 millimeters with 5.0 millimeters Between.
9. The multichannel micro-fluidic chip dress simultaneously detecting multiple hypotype swine flue the most according to claim 1 Put, it is characterised in that the structure of this micro fluidic device also includes higher-order of oscillation electric signal generator, described height Frequency vibration is swung its other end of electric signal transmission cable and is connected with this higher-order of oscillation electric signal generator.
10. The multichannel micro-fluidic chip dress simultaneously detecting multiple hypotype swine flue the most according to claim 1 Put, it is characterised in that its specified ultrasonic emitting power of this miniature ultrasonic transducer units is between 2 milliwatts and 2000 Between milliwatt, the frequency of its ultrasound wave operationally launched of this miniature ultrasonic transducer units be between Between 100KHz and 12MHz.