CN106153701A - Detect multiple hypotype swine flue Dual Drive CGCM micro flow control chip device - Google Patents

Abstract

The present invention relates to the multiple hypotype swine flue Dual Drive CGCM micro flow control chip device of a kind of detection, belong to analysis field tests.Use the polydimethylsiloxane inexpensively and easily processed i.e. PDMS to make the substrate of hypotype swine flue diagnosis micro-fluidic chip, there is a series of obstacle；This case is for this obstacles.This case is characterized by, the PDMS with ecosystem surface selected by substrate, and in sample its neighbor positions of liquid stream terminal fixing installing miniature ultrasonic transducer units of this micro-fluidic chip, interfacial tension is reduced with ultrasound wave, utilize the PDMS strong absorbability to ultrasound wave simultaneously, reach ultrasonic intensity rapid decrement in short distance, thus interfacial tension difference is formed at the two ends of this chip, this difference provides a kind of and drives the strength that sample liquid stream flows to this terminal direction along hydrophobic capillary channel, this strength and simultaneously with its mechanicalness of Micropump pumping strength Collaboration of comprising in structure, described obstacles is thus addressed.

Description

Detect multiple hypotype swine flue Dual Drive CGCM micro flow control chip device

Technical field

The present invention relates to the multiple hypotype swine flue Dual Drive CGCM micro flow control chip device of a kind of detection, belong to analysis test Field.

Background technology

Multichannel micro-fluidic hypotype swine flue diagnostic techniques background, may refer to the patent of invention Shens such as CN 201110311127.1 Please case.

Only for itself overall general picture of microflow control technique, 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 ", this monograph is published by Science Press, and this monograph is to microflow control technique Past, now, and, vision of the future etc. aspect, suffer from detailed, 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 the substrate being etched with small fluid course and the cover plate fit together therewith, Small fluid course on described substrate, before fit on cover plate, apparent on see to be exactly some micro-channel, wait until thereon After covering cover plate, just real Guan Bi forms described small fluid course, and the conduit inner surface of this 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 completes 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 this micro-channel The state on surface or character substantially determine integrality or the character of this small fluid course；Therefore saying, this builds at base Inner surface state or the inner surface character of the micro-channel on sheet are key factors；In principle, any can keep or substantially protect Hold the material of its solid forms, can be used to make substrate and cover plate, such as, it is possible to the material as substrate and cover plate is permissible It is monocrystalline silicon piece, piezoid, sheet glass, high polymer such as polydimethylsiloxane, polymethyl methacrylate, Merlon etc. Deng；Certainly, the selection of substrate can be identical with the selection of cover plate, it is also possible to differs；From material consumption, manufacture difficulty and From the point of view of application popularization prospect etc. aspect, there is the selection of the least difference, especially that substrate between these materials, impact is relatively Greatly.

In various substrates make material, polydimethylsiloxane, i.e. PDMS, the easiest molding, so Substrate on to make micro-channel extremely simple, and this lower cost for material, make substrate with this polydimethyl siloxane material, Suppress or etch micro-channel thereon, and the cover plate made with glass or the cheap material such as polypropylene or other plastic sheet matches, 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, promote.

But, thing is really not so simply.

One, this polydimethyl siloxane material, the material that i.e. abbreviation letter PDMS is referred to, itself is a kind of strong Hydrophobic material, builds micro-channel on this material, if not carrying out the modified operation for this micro-channel surface, then, After entirety has been assembled, after i.e. covering cover plate, lead to because its inner surface of described micro-channel in structure occupies most liquid stream The inner surface in road, then, this its strong hydrophobic property of PDMS micro-channel inner surface, is deciding factor, and it can make class Be similar to aqueous solution the fine liquid stream of polar liquid by becoming the most difficult, its flow resistance is big, and the most general Micropump is all It is 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 modifying particular for the micro-channel inner surface on this PDMS material, is necessary Operation；So, this operates pretty troublesome for the modification of PDMS micro-channel inner surface？That is not this problem, structure Become serious technical puzzlement, be another problem: the PDMS polymer molecule tool that this its body of PDMS material substrate is internal mutually Having the characteristic automatically diffusing to the surface, migrating, this substrate body internal PDMS polymer molecule mutually automatically diffuses to the surface, moves The characteristic moved, can not maintain foot by making the state after the modification of that its inner surface of micro-channel of surface modification modification The enough long time, holding time of its inner surface state of the micro-channel after that is surface-modified has substantially been only sufficient in laboratory The time of portion's test experiments needs；In other words, through this PDMS micro-channel inner surface that surface modification or surface are modified, its After modification or say the apparent condition formed after modification can not be lasting, but automatically tend to soon or say become surface again and change Apparent condition before property, returns to the most hydrophobic apparent condition of that script in relatively short period of time, then, just think, Such micro-fluidic chip can make in a large number, mass storage, be widely popularized, and answer is clearly, that is, it is impossible to. Micro-channel on this PDMS material, if not doing surface modification, the fine liquid stream of polar solvent being similar to aqueous solution cannot pump Sending and pass through, chip the most just cannot use；And if done surface modification, the state after cannot persistently keeping again it to modify, also It is equally cannot popularization and application.

So, how to accomplish to utilize cheap PDMS material to make substrate, and table in described micro-channel can be released Face decorating state cannot persistently, chip cannot make in a large number, lay in a large number and then be widely popularized and such a make this area numerous specially The puzzlement that industry personnel are entangled with for a long time, it is simply that the highly difficult problem that its obvious technology barrier 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 most hydrophobic Material surface and also another problem, that is, biomacromolecule can be adsorbed in the most hydrophobic this PDMS surface, and And, the depression that these adsorbed biomacromolecules also can be further on PDMS surface further, gradually falls into gradually deep, directly To the heavy body phase being trapped in PDMS substrate, in fact, this process, partly it is also due to PDMS material body internal mutually Polymer molecule have diffuse to the surface, travel motion is caused；This situation, it is also possible to explain from another angle, i.e. Internal to its diffusion into the surface, those polymer molecules of migration, the result of its motion mutually by PDMS body continuously, be by Within those gradually have been involved in the body phase of PDMS substrate by the biomacromolecule of surface adsorption, briefly, these are inhaled Attached biomacromolecule is swallowed up mutually by PDMS substrate body exactly；So, this PDMS substrate body swallows up biomacromolecule mutually Phenomenon, its impact caused, necessarily cause the severe deviations relating to all kinds of test data of experiment of biomacromolecule.

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 stop because of the saturated absorption in surface, but, no Disconnected adsorbed, the most constantly swallowed up.

About PDMS substrate in related experiment test process its body the most constantly swallow up test associated biomolecule macromole phenomenon, separately A kind of explanation is to say, PDMS body mutually in there is substantial amounts of Minute pores, associated biomolecule macromole by after surface adsorption, depression Enter these Minute pores, and then swallowed up；But, inventor thinks, those can allow that the air of miniature scale divides Son clamp-ons described Minute pores therebetween, is not equal to them and also can directly allow that the biomacromolecule of relatively large yardstick enters, and two Person's difference on yardstick is huge, must not make sweeping generalizations.Bypass explanation, in any case, analyze the biology of object as dependence test Macromole is adsorbed by PDMS substrate micro-channel inner surface, and then is constantly swallowed up by PDMS substrate body phase, and this is known objective The phenomenon existed.

In order to stop the effect of swallowing up relative to biomacromolecule of this PDMS substrate body, can be from containment PDMS surface to life The absorption of thing macromole addresses, and way is aiming at this PDMS material surface and is chemically modified modification, for From the point of view of PDMS is the situation of substrate material, it is simply that the surface of described micro-channel part is chemically modified modification, Jing Guohua Learn the described micro-channel inner surface of modification, it is possible to contain its absorption to biomacromolecule, and then avoid biomacromolecule quilt PDMS substrate body is swallowed up mutually；But, or that old problem, that is, the chemical modification on PDMS material surface changes Apparent condition after property cannot persistently keep, the internal mutually polymer molecule of this PDMS substrate body its automatically diffuse to the surface, The process migrated, can become that again script strong through the micro-channel inner surface state that surface chemical modification is modified soon and dredge Water and the state of strong adsorption biomacromolecule, in other words, no matter how professionals in the field turn from side to side, this PDMS Its micro-channel inner surface of substrate is the most rapidly to strong hydrophobic surface state evolution.

So, how can either obtain that PDMS material price is the cheapest, substrate makes extremely easy benefit, can reach again Growth stage contains this PDMS substrate micro-channel inner surface absorption process to biomacromolecule, and then stops PDMS substrate body phase The effect of swallowing up to biomacromolecule so that related chip manufactured goods are able to maintain that a shelf-life the most long, rational, It it is exactly a difficult problem the most thorny.This difficult problem, as another difficult problem addressed above, makes the numerous specialty in this area equally Personnel are entangled with for a long time, perplex, and this difficult problem is the highly difficult problem that its obvious technology barrier can not be despised equally.This difficulty Having there are a lot of days in topic, up to now, is the most not yet properly settled.

Its three, as it has been described above, this PDMS micro-channel inner surface is the most hydrophobic, and surface chemical modification targetedly or come to the surface Learning to modify is difficult to again persistently, therefore, actual can only still belong to the shortest in the apparent condition after its surface modification or surface are modified It is used within phase；If have passed through that ofer short duration expiry date, and if using by force, due to surface shape State, the most again near hydrophobic state, uses usual Micropump to drive sample liquid stream then to certainly exist bigger flow resistance, So, just test liquid can only be forced to flow to target direction flowing by strengthening Micropump pump power and pumping pressure, as it has been described above, This PDMS material is soft, pumps sample liquid stream with pumping pressure too high, machinery, and it enters will to cause this substrate Sample end include sample introduction end near zone described micro-channel generation bubbling, expanded, distort, deform, and, this high-pressure situations Under, it is in this sample introduction end and the micro-channel of near zone thereof and periphery is also susceptible to the stripping between substrate and cover plate, these feelings Under shape, sample solution will enter the crack of the appearance between substrate and the cover plate formed after described stripping and flow over everywhere, and this is real Border causes the damage of this micro-fluidic chip；Certainly, if this surface modification or surface are modified the most not in place, also result in Within of short duration usual effect duration, said circumstances occurs；In the case of the additional Micropump of simple employing carries out liquid stream driving, above-mentioned This problem exists all the time.If as it has been described above, entirely without doing the pre actions such as any described surface modification or surface modification, So, this problem above-mentioned by even more serious, even without occur micro-channel bubbling described in sample introduction end and near zone thereof, expanded, Distortion, the problem such as stripping between deformation and substrate and cover plate, merely because this flow resistance is excessive, use high pressure Micropump the most not Sample liquid stream must be driven to march forward towards terminal side.

Summary of the invention

The technical problem to be solved is to provide a package solution, solves three addressed above simultaneously The a series of difficult problem the most mutually involved together of aspect, and, this solution is applied to the diagnosis of hypotype swine flue Use multichannel micro-fluidic chip field, form a kind of novel hypotype swine flue diagnosis multichannel micro-fluidic chip device.

The present invention solves described technical problem by following scheme, and the device that the program provides is a kind of detection multiple hypotype pig stream Sense Dual Drive CGCM micro flow control chip device, the structure of this device includes multichannel micro-fluidic chip, this micro-fluidic chip Structure include bonded to each other being installed in substrate together and cover plate, described substrate and cover plate are plate object or tablet, this base The channel structure formed via mould pressing process or etching technics is contained in that face towards this cover plate of sheet, bonded to each other is arranged on one This substrate risen and this cover plate have been built into the micro-fluidic chip containing pipeline configuration jointly, and the locations of structures of this pipeline is positioned at this base The juncture area that sheet is bonded to each other with this cover plate, the two ends of this pipeline are respectively with the sample introduction end of this micro-fluidic chip and terminal even Connecing, this sample introduction end is the injection end of this micro-fluidic chip sample solution, this terminal be this micro-fluidic chip actual sample introduction test time its The terminal of sample solution flowing in chip, this terminal is located remotely from each other with this sample introduction end, and the distance between this terminal and this sample introduction end is situated between Between 3 centimetres and 10 centimetres, in this pipeline, on diverse location, sequentially it is equiped with working electrode and to electrode and reference Electrode, described working electrode is resisted by conductive electrode and the hypotype swine flue specificity that embedded that is attached on this conductive electrode Former gold size sensitive membrane is constituted, and the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is by three laterals also Connection is constituted, and the quantity of described working electrode is three, and the installation position of these three working electrodes lays respectively at described three branched pipes In road, and, the specific antigen in its top layer gold size sensitive membrane structure of these three working electrodes is to resist hypotype swine flue respectively Three kinds of hypotype swine flue antigenic substances that physical ability is specific binding, these three kinds of antigenic substances are hypotype swine flue specific antigen respectively H₁N₁、H₃N₂And H₁N₂, its material of described working electrode is gold material or thermal decomposition conducting polymer material, described working electrode Its pattern presents lamellar or thread, it is important that, its material of this substrate is polydimethylsiloxane material, and its surface of this substrate 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 any surface chemistry The surface of the primary form of this modified material, the structure of this device also includes miniature ultrasonic transducer units, and, the higher-order of oscillation Electric signal transmission cable, one end of this higher-order of oscillation electric signal transmission cable links together with this miniature ultrasonic transducer units, should Miniature ultrasonic transducer units 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 miniature Its major function of ultrasonic transducer is when the actual sample introduction of micro-fluidic chip is tested, and utilizes its ultrasound wave launched to reduce examination Interfacial tension between the inwall of sample solution and this its inner passage of micro-fluidic chip so that it is can be compatible, and, utilize described Distance difference between sample introduction end and described terminal and this miniature ultrasonic transducer units installation position and its experienced super Difference on intensity of acoustic wave, difference between its interfacial tension of sample introduction end and its interfacial tension of described terminal described in induced synthesis, should Interfacial tension difference between these two ends of micro-fluidic chip can form pressure gap, this pressure between these two ends of this micro-fluidic chip Power difference can drive sample solution to described end flow；Its function of this miniature ultrasonic transducer units also included with surpassing that it is launched Sound wave checks its absorption on its inner passage inner surface of this micro-fluidic chip 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；Soft and have elasticity this poly-two Its function of the substrate of methylsiloxane material includes, with the character of its absorption strong to ultrasound wave, strongly absorbing ultrasound wave, And thereby realize the quick of ultrasonic intensity within limited short distance between this terminal of this micro-fluidic chip to this sample introduction end Successively decrease；And, Micropump, this Micropump is connected with this sample introduction end；The function of this Micropump is, at this sample solution and this micro-fluidic core The precondition that interfacial tension between the inwall of its inner passage of sheet is reduced by this ul-trasonic irradiation, the alternate compatibility increases Under, it is brought to carry out the interfacial tension difference between the described two ends of this ultrasound wave induction with the mechanicalness pumping strength of this Micropump Driving force support mutually, adjust mutually, be mutually coupled, pool in the way of Collaboration one drive test liquid flow to The strength of described terminal direction flowing.

Itself art-recognized meanings of described Micropump one word is known for the professional in micro-fluidic chip field.

Described Micropump both can be with the Micropump being external form；This Micropump can also be to do into or say inside this micro-fluidic chip of embedding The Micropump of the built in version of its sample introduction end structure position or this sample introduction end Near-neighbor Structure position.

Piezoelectric pump, miniature peristaltic pump or the miniature air driven pump that described Micropump is the most miniature.

Described gold size sensitive membrane is to be sufficiently mixed uniformly by chitosan gold size solution and hypotype swine flue specific antibody solution, uses Point sample instrument point sample or coat specified structure position, and make its drying and forming-film form.Hypotype swine flue in described gold size sensitive membrane Specific antibody is the hypotype swine flue antibody of horseradish peroxidase or glucose oxidase labelling, described gold size sensitive membrane Being included as fixing above-mentioned each hypotype swine flue specific antibody and introduced complementary medium therein, described complementary medium is such as Chitosan, cellulose acetate, gelatin be therein a kind of or their mixture.

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

Relate in structure is minute sized electrode to electrode and reference electrode, and its electrode shape may each be arbitrarily choosing Fixed shape, described arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..Described to electricity Itself the art-recognized meanings of vocabulary of pole and described reference electrode is known.

Only for itself the art-recognized meanings of the ultrasonic transducer one word professional for ultrasonic technology field, it is public Know.

Various sizes, variously-shaped ultrasonic transducer are commercially available；Its size of commercially available miniature ultrasonic transducer units is permissible Little 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 itself and Speech, for the professional in ultrasonic technology field, is known general technology.This is not launched superfluous words by this case.

Only itself micro-channel of naked PDMS substrate is molded or for lithographic technique, be open-and-shut known technology.

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 electric signal transmission electricity Its other end of 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 in ultrasonic technology field, be Simple and known；Described higher-order of oscillation electric signal generator can customize to ultrasonic instrument specialized factory.

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

This case device can further include some adnexaes certainly, described adnexa such as multiple tracks electrochemical workstation etc., institute The art-recognized meanings stating multiple tracks electrochemical workstation is known.Each working electrode of relating in this case microfluidic chip structure and To electrode and reference electrode etc., can be respectively via the most special the corresponding interface got lines crossed with described multiple tracks electrochemical workstation Couple.Described special each the corresponding interface being used to each described electrode with described multiple tracks electrochemical workstation of getting lines crossed is carrying out phase The private cable being mutually coupled with.Described micro-fluidic chip in this case device, its structure can also include micro-valve, the number of described micro-valve Amount does not limits, according to actual needs, and 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 known；This micro-valve The manufacturing technology of itself and use technology are also known；This optional component of micro-valve.

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；The length of described working electrode can permit Permitted the length being easily installed use being arbitrarily set, it is however recommended to or to say preferred its scope of described length be at 1 micron Between 15000 microns.

The described gold size being installed in described working electrode surface layer by spraying or point sample instrument point sample or the coating of other appropriate process is quick Sense film, its thicknesses of layers can allow the thickness that the sample measuring liquid the treated generation electrical signals being arbitrarily set responds, but, push away The thickness recommended the most preferably thickness is between 10 nanometers and 200 nanometers.

Described cover plate in chip structure, its material can allow to be any electrical insulating property material, such as: polypropylene, glass Glass, polymethyl methacrylate, polydimethylsiloxane, etc., in order to make smaller size of micro-fluidic chip, such as do Become the micro-fluidic chip of the super-small of length only 2.0 centimetres to 3.0 centimetres, and realize ultrasound wave in the distance that this is extremely short Extremely fast decay, it may be preferred to polydimethylsiloxane is used as cover plate.Certainly, large-sized micro-fluidic chip selects Use polydimethylsiloxane to be used as described cover plate, be also that this case technical scheme is allowed.

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

The using method of this case micro-fluidic chip:

This case drives liquid stream to flow in the capillary channel of this triple channel micro-fluidic chip with described Dual Drive coupling operating mode, Multi-channel electrochemical analyzer device is utilized respectively three kinds of hypotype swine flue diagnostic antigens to be detected.

Detect corresponding three kinds of hypotype swine flue antibody with three kinds of hypotype swine flue antigens, come with three kinds of hypotype swine flue antibody Detect corresponding three kinds of hypotype swine flue antigens, similarly, corresponding hypotype swine flue can be diagnosed；The principle of its foundation It is, necessarily antigen, antibody deposit in hypotype swine flue patient, and mutually Reversible binding, forms reversible conjugate, because of This, detect antibody with antigen and thereby diagnose corresponding hypotype swine flue, goes detect antigen and diagnose corresponding sub-with antibody Type swine flue, can reach diagnostic purpose.Certainly, its corresponding electrode sensitive decorative layer of different means is the most not Identical.

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

1, in micro-pipeline, blood serum sample liquid is added, under described Dual Drive coupling operating mode drives, various hypotype swine flue Antibody molecule is flowed by the hypotype pig of the corresponding horseradish peroxidase-labeled of gold size sensitive membrane embedding on electrode surface in each passage Sense specific antigen capture.

2, the hypotype swine flue specific antigen of horseradish peroxidase-labeled is formed with the hypotype swine flue antibody in blood serum sample Immune complex.

3, use multi-channel electrochemical analyzer, add the electron mediators such as catechol, use the above-mentioned reaction of amperometric detection The curent change caused, is 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 miniature ultrasonic and changed with attaching Energy device, utilizes its low-power launched of this miniature ultrasonic transducer units, the ultrasound wave of high-frequency band so that without coming to the surface The compatibility learned between modified this most hydrophobic its tube wall of micro-fluidic chip internal pipeline and test object water solution significantly increases Add, this for sample liquid stream by providing a realistic possibility；Meanwhile, utilize polydimethylsiloxane substrate its to ultrasonic The strong absorbability of ripple, in comparatively short distance, it is, the only several centimeters from described terminal to described sample introduction end In the shortest distance of yardstick, reaching the rapid decrement of ultrasonic intensity, thereby institute is caused at the described two ends at this micro-fluidic chip Stating the difference of interfacial tension, the difference of the interfacial tension between these two ends can cause a kind of driving force, and this kind is poor because of interfacial tension Its function of driving force that is different and that cause is to drive sample liquid stream in the most hydrophobic capillary channel to described terminal side To flowing；And simultaneous described Micropump in structure, its function is, this sample solution and this micro-fluidic chip inside it logical Under the precondition that interfacial tension between the inwall in road is reduced by this ul-trasonic irradiation, the alternate compatibility increases, with this Micropump Mechanicalness pumping strength come and this ultrasound wave induction described two ends between its driving force brought of interfacial tension difference Support mutually, adjust mutually, be mutually coupled, in the way of Collaboration, pool one drive test liquid to flow to described terminal side Strength to flowing；The existence of this Micropump so that its ultrasonic emitting intensity of this miniature ultrasonic transducer units can be allowed to appropriateness Reducing, this is particularly suitable for for the situation containing ultrasound wave sensitive composition in detection object；And due to this ultrasonic transducer and The existence of radiated ultrasound wave, it is possible to increase the alternate compatibility, reduce interfacial tension, and provide this two ends interfacial tension difference its The special driving force brought, then, in this case, its flow resistance in this micro-channel of sample liquid stream significantly drops Low, correspondingly, its running resistance of this Micropump is greatly reduced, and so, this Micropump just can be to carry out than relatively low pumping pressure For the pumping work of described sample solution, owing to mechanical pumping pressure is greatly reduced, therefore, in such a situation, Just it is not susceptible to the described micro-channel drum of described sample introduction end and the near zone thereof caused because sample introduction terminal tool pumping pressure is excessive Steep, expand, deform, distort and stripping etc. problem between this region substrate and cover plate；The coupling running of this Dual Drive of this case Scheme and add for this sample fluid flow action handling, it is possible to allow to use ultrasonic intensity, ultrasonic frequency, Micropump pump power, Micropump pumping pressure etc. multiple indexs include flowing forward for flow rate, the flowing action of this flowing Dynamic or time-out flowing or acceleration flowing etc. flowing action carries out multiparameter and accurately manipulates；Running side is coupled by this Dual Drive of this case Case, repaiies entirely without its micro-channel of substrate of this polydimethylsiloxane material etc. relevant surfaces being carried out any surface chemistry Decorations or surface chemical modification, altogether dispensed with the laborious procedures of this surface chemical modification or surface chemical modification；On the other hand, should Low-power, the ultrasound wave of high-frequency band, additionally it is possible to the biomacromolecule in containment sample is at this literalness naked poly dimethyl silicon Absorption on its inner surface of pipeline of oxyalkyl sheet, and then contain this polydimethylsiloxane substrate the most described biomacromolecule of its body The effect of swallowing up；Described antigen, antibody and antigen are the most all belonging to described biomacromolecule with the Reversible binding thing of antibody Type；Owing to described adsorption and the described effect of swallowing up are contained effectively, therefore, dependence test result will more Add and can reflect practical situation objectively；This low-power, the effect of high-frequency band ultrasound wave, the most also include facilitating antigen, resisting Quickly reaching of Reversible binding reaction between body, this makes dependence test operate can be to complete than speed faster.

As it has been described above, the existence of this Micropump so that its ultrasonic emitting intensity of this miniature ultrasonic transducer units can be allowed to fit Degree reduces, then, this feature contributes to protecting its sensitive coating of described working electrode, is allowed to from ultrasound injury.

Based on this case scheme, completely without carrying out repairing for the surface chemistry of this polydimethylsiloxane its relevant surfaces of substrate 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 polymeric thing molecule of this polydimethylsiloxane substrate the most automatically diffuses to the surface, migrates what it was caused The damaging influence of described surface chemical modification layer or surface chemical modification layer is not existed.

The technical scheme of this case has dissolved relevant to its application of polydimethylsiloxane substrate addressed above totally Row technical barrier.Based on this case scheme, this kind the most inexpensively and easily polydimethyl siloxane material of processing and fabricating just has can Can at this micro-fluidic chip, it be prepared, produces, application etc. field plays bigger effect.

Accompanying drawing explanation

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

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

Detailed description of the invention

In this embodiment of this case that Fig. 1 is shown, the structure of this device includes multichannel micro-fluidic chip, this micro-fluidic core The structure of sheet includes bonded to each other being installed in substrate 1 together and cover plate 2, and described substrate 1 and cover plate 2 are plate object or sheet Shape thing, the channel structure formed via mould pressing process or etching technics, phase are contained in that face towards this cover plate 2 of this substrate 1 It is jointly mounted to this substrate 1 together mutually and is jointly built into the micro-fluidic chip containing pipeline configuration with this cover plate 2, this pipeline Locations of structures be positioned at the juncture area that this substrate 1 is bonded to each other with this cover plate 2, the two ends of this pipeline respectively with this micro-fluidic core Sample introduction end 5 and the terminal 6 of sheet connect, and this sample introduction end 5 is the injection end of this micro-fluidic chip sample solution, and this terminal 6 is The terminal of sample solution flowing in its chip during the test of this micro-fluidic chip actual sample introduction, this terminal 6 is the most remote with this sample introduction end 5 From, the distance between this terminal 6 and this sample introduction end 5 is between 3 centimetres and 10 centimetres, in this pipeline on diverse location Sequentially being equiped with working electrode and to electrode and reference electrode, described working electrode is by conductive electrode and is attached to this and leads The gold size sensitive membrane having embedded hypotype swine flue specific antigen on conductive electrodes 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, these three work The installation position of electrode lays respectively in described three laterals, and, its top layer gold size sensitive membrane knot of these three working electrodes Specific antigen in structure is three kinds of hypotype swine flue antigenic substances that can be specific binding to hypotype swine flue antibody respectively, and these are three years old Planting antigenic substance is hypotype swine flue specific antigen H respectively₁N₁、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 important that, this its material of substrate 1 Being polydimethylsiloxane material, this its surface of substrate 1 is the surface of primary form, the surface of this primary form its be meant to It is not through the surface of primary form of this material of any surface chemical modification or any surface chemical modification, the knot of this device Structure also includes miniature ultrasonic transducer units 4, and, higher-order of oscillation electric signal transmission cable 3, this higher-order of oscillation electric signal transmits One end of cable 3 links together with this miniature ultrasonic transducer units 4, and this miniature ultrasonic transducer units 4 is installed in this with attaching The cover plate 2 of micro-fluidic chip or the position of the neighbouring described terminal 6 of substrate 1；Its main merit of this miniature ultrasonic transducer units 4 Can be when the actual sample introduction of micro-fluidic chip is tested, utilize its ultrasound wave launched to reduce sample solution and this micro-fluidic chip Interfacial tension between the inwall of its inner passage so that it is can be compatible, and, utilize described sample introduction end 5 and described terminal Distance difference between 6 and this miniature ultrasonic transducer units 4 installation position and the difference on its ultrasonic intensity experienced Different, difference between its interfacial tension of sample introduction end 5 and its interfacial tension of described terminal 6 described in induced synthesis, this micro-fluidic chip Interfacial tension difference between these two ends 5,6 can form pressure gap between these two ends 5,6 of this micro-fluidic chip, should Pressure gap can drive sample solution to flow to described terminal 6 direction；This its function of miniature ultrasonic transducer units 4 also includes with it The ultrasound wave launched check in sample contained biomacromolecule its on its inner passage inner surface of this micro-fluidic chip Absorption, and then check its body of substrate 1 effect of swallowing up relative to this biomacromolecule of this polydimethylsiloxane material；Softness is also Its function of substrate 1 of this polydimethylsiloxane material that tool is elastic includes with the character of its absorption strong to ultrasound wave, to ultrasonic Ripple absorbs strongly, and thereby real within this terminal 6 of this micro-fluidic chip arrives the limited short distance between this sample introduction end 5 The rapid decrement of existing ultrasonic intensity；And, Micropump 7, this Micropump 7 is connected with this sample introduction end 5；The function of this Micropump 7 is, Interfacial tension between this sample solution with the inwall of this its inner passage of micro-fluidic chip is reduced by this ul-trasonic irradiation, phase Between under the precondition that increases of the compatibility, with the mechanicalness of this Micropump 7 pump strength come the described two ends 5 with the induction of this ultrasound wave, Its driving force brought of interfacial tension difference between 6 is supported mutually, adjusts mutually, is mutually coupled, with Collaboration Mode pools one and drives test liquid to flow to the strength of described terminal 6 direction flowing.

Arrow in legend indicate this micro-fluidic chip its when actual motion, driven by two ends 5,6 pressure differential, its examination The flow direction of sample liquid stream.

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

Involved miniature ultrasonic transducer units 4 is commercially available；Can also customize to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal transmission cable 3 is commercially available；Can also customize to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；Can also customize to relevant manufacturers.

Micropump 7 involved by legend can customize to specialized factory.

Involved its inner passage of this micro-fluidic chip of this case is the pipeline of hydrophobic capillary tube form.

Described Micropump both can be with the Micropump being external form；This Micropump can also be to do into or say inside this micro-fluidic chip of embedding The Micropump of the built in version of its sample introduction end structure position or this sample introduction end Near-neighbor Structure position.Micropump in legend is external form Micropump；This Micropump can certainly do into or say the embedding internal sample introduction end of this microfluidic chip structure or its Near-neighbor Structure position The Micropump of described built in version, its basic structure key element is identical with the Micropump of external form.

Each working electrode in this example structure and can be respectively via the most special cable or say to electrode and reference electrode Get lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as adnexa or say interface of getting lines crossed and couple.

Claims (10)

1. detecting multiple hypotype swine flue Dual Drive CGCM micro flow control chip device, the structure of this device includes that multichannel is micro- Fluidic chip, the structure of this micro-fluidic chip includes bonded to each other being installed in substrate together and cover plate, and described substrate and cover plate are equal For plate object or tablet, the conduit formed via mould pressing process or etching technics is contained in that face towards this cover plate of this substrate Structure, this substrate being installed together bonded to each other and this cover plate have jointly been built into the micro-fluidic chip containing pipeline configuration, have been somebody's turn to do The locations of structures of pipeline is positioned at the juncture area that this substrate is bonded to each other with this cover plate, the two ends of this pipeline respectively with this micro-fluidic core The sample introduction end of sheet and terminal connect, and this sample introduction end is the injection end of this micro-fluidic chip sample solution, and this terminal is that this is micro-fluidic Chip actual sample introduction test time its chip in sample solution flowing terminal, this terminal is located remotely from each other with this sample introduction end, this terminal and Distance between this sample introduction end, between 3 centimetres and 10 centimetres, is sequentially equiped with work electricity in this pipeline on diverse location Pole and to electrode and reference electrode, described working electrode is by conductive electrode and is attached to the embedding on this conductive electrode The gold size sensitive membrane of hypotype swine flue specific antigen is constituted, the structure of this pipeline is parallel construction, described in parallel construction Pipeline is made up of three lateral parallel connections, and the quantity of described working electrode is three, and the installation position of these three working electrodes divides It is not positioned at described three laterals, and, the specific antigen in its top layer gold size sensitive membrane structure of these three working electrodes Being the three kind hypotype swine flue antigenic substances specific binding to hypotype swine flue antibody energy respectively, these three kinds of antigenic substances are respectively Hypotype swine flue specific antigen H₁N₁、H₃N₂And H₁N₂, its material of described working electrode is gold material or thermal decomposition conductive polymer Sub-material, its pattern of described working electrode presents lamellar or thread, it is characterised in that its material of this substrate is polydimethylsiloxanes Alkane 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 any table The surface of the primary form of this material of face chemical modification or any surface chemical modification, the structure of this device also includes miniature ultrasonic Wave transducer, and, higher-order of oscillation electric signal transmission cable, one end of this higher-order of oscillation electric signal transmission cable is miniature super with this Acoustic wave transducer links together, and this miniature ultrasonic transducer units is installed in the cover plate of this micro-fluidic chip or the neighbour of substrate with attaching The position of nearly described terminal；Its major function of this miniature ultrasonic transducer units is when the actual sample introduction of micro-fluidic chip is tested, and utilizes Its ultrasound wave launched is to reduce the interfacial tension between the inwall of sample solution and this its inner passage of micro-fluidic chip so that it is Can be compatible, 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 described terminal its Difference between interfacial tension, the interfacial tension difference between these two ends of this micro-fluidic chip can be at these two ends of this micro-fluidic chip Between formed pressure gap, this pressure gap can drive sample solution to described end flow；Its merit of this miniature ultrasonic transducer units Can also include with its ultrasound wave launched check in sample contained biomacromolecule its this micro-fluidic chip inside it logical Absorption on road inner surface, and then check its body of the substrate work that swallows up relative to this biomacromolecule of this polydimethylsiloxane material With；Soft and this polydimethylsiloxane material of having elasticity its function of substrate includes with the property of its absorption strong to ultrasound wave Matter, absorbs strongly to ultrasound wave, and thereby limited short distance between this terminal of this micro-fluidic chip to this sample introduction end Within realize the rapid decrement of ultrasonic intensity；And, Micropump, this Micropump is connected with this sample introduction end；The function of this Micropump is, Interfacial tension between this sample solution with the inwall of this its inner passage of micro-fluidic chip is reduced by this ul-trasonic irradiation, phase Between under the precondition that increases of the compatibility, pump strength with the mechanicalness of this Micropump and come between the described two ends of this ultrasound wave induction Its driving force brought of interfacial tension difference support mutually, adjust mutually, be mutually coupled, converge in the way of Collaboration Being polymerized to one drives test liquid to flow to the strength of described terminal direction flowing.

Detection the most according to claim 1 multiple hypotype swine flue Dual Drive CGCM micro flow control chip device, it is special Levying and be, described pipeline includes that described lateral is capillary channel.

Detection the most according to claim 1 multiple hypotype swine flue Dual Drive CGCM micro flow control chip device, it is special Levying and be, described thermal decomposition conducting polymer is the electric conductivity material formed after anoxybiotic heat treatment by polyimides or polyacrylonitrile Material.

Detection the most according to claim 1 multiple hypotype swine flue Dual Drive CGCM micro flow control chip device, it is special Levy and be, the width of described working electrode or diameter between 0.1 micron to 2000 micron, and, described working electrode Length between 1 micron to 15000 micron.

Detection the most according to claim 1 multiple hypotype swine flue Dual Drive CGCM micro flow control chip device, it is special Levying and be, the thickness of described gold size sensitive membrane is between 10 nanometers and 200 nanometers.

Detection the most according to claim 1 multiple hypotype swine flue Dual Drive CGCM micro flow control chip device, it is special Levying and be, its material of described cover plate in structure is polydimethylsiloxane material.

Detection the most according to claim 1 multiple hypotype swine flue Dual Drive CGCM micro flow control chip device, it is special Levying and be, described Micropump is miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.

Detection the most according to claim 1 multiple hypotype swine flue Dual Drive CGCM micro flow control chip device, it is special Levying and be, described cover plate in structure and its thickness of substrate are all between 1.0 millimeters and 5.0 millimeters.

Detection the most according to claim 1 multiple hypotype swine flue Dual Drive CGCM micro flow control chip device, it is special Levying and be, the structure of this micro fluidic device also includes higher-order of oscillation electric signal generator, described higher-order of oscillation electric signal transmission cable Its other end is connected with this higher-order of oscillation electric signal generator.

Detection the most according to claim 1 multiple hypotype swine flue Dual Drive CGCM micro flow control chip device, it is special Levying and be, its specified ultrasonic emitting power of this miniature ultrasonic transducer units is between 2 milliwatts and 2000 milliwatts, and this is miniature The frequency of its ultrasound wave operationally launched of ultrasonic transducer is between 100KHz and 12MHz.