CN106290492A - Driving component is easily-disassembled and cholera diagnosis device more capable of circulation - Google Patents

Abstract

The present invention relates to a kind of drive and capable of circulation cholera diagnosis device again easily-disassembled with component, belong to analysis field tests.There is a series difficult problem in the substrate making cholera diagnosis micro-fluidic chip of polydimethylsiloxane that inexpensively and easily processing i.e. PDMS；This case is for this series difficult problem.This case is characterized by, the PDMS with ecosystem surface selected by substrate, and the elastic clip of miniature ultrasonic transducer units will be attached on its clamping limb with elastic force snap-in location in sample its neighbor positions of liquid stream terminal 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 intercoupling with its mechanicalness of Micropump pumping strength of comprising in structure, Collaboration.

Description

Driving component is easily-disassembled and cholera diagnosis device more capable of circulation

Technical field

The present invention relates to a kind of drive and capable of circulation cholera diagnosis device again easily-disassembled with component, this device is based on antigen The reaction of/antibody specificity carrys out the special purpose device of cholera diagnosis antigen, belongs to analysis field tests.

Background technology

Associated multi-channel micro-fluidic cholera diagnostic techniques background, may refer to CN 200910150930.4 application for a patent for invention such as grade 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 cholera diagnosis manifold Micro-fluidic chip field, road, forms a kind of novel cholera diagnosis Multichannel device.

The present invention solves described technical problem by following scheme, and the device that the program provides is that a kind of driving component is easily-disassembled And cholera diagnosis device more capable of circulation, the structure of this device includes multichannel micro-fluidic chip, the knot of this micro-fluidic chip Structure includes bonded to each other being installed in substrate together and cover plate, and described substrate and cover plate are plate object or tablet, this substrate That face towards this cover plate contains the channel structure formed via mould pressing process or etching technics, bonded to each other is installed together This substrate and this cover plate have been built into the micro-fluidic chip containing pipeline configuration jointly, the locations of structures of this pipeline be positioned at this substrate with The juncture area that this cover plate is bonded to each other, the two ends of this pipeline are connected with sample introduction end and the terminal of this micro-fluidic chip respectively, should Sample introduction end is the injection end of this micro-fluidic chip sample solution, when this terminal is the test of this micro-fluidic chip actual sample introduction in its chip The terminal of sample solution flowing, 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 between 3 lis Between rice 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 quick by conductive electrode and the gold size having embedded cholera specific antibody that is attached on this conductive electrode Sense film is constituted, and the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is made up of four lateral parallel connections, institute The quantity stating working electrode is four, and the installation position of these four working electrodes lays respectively in described four laterals, and, Specific antibody in its top layer gold size sensitive membrane structure of these four working electrodes respectively can be specific binding to cholera antigen Four kinds of cholera antibody materials, these four kinds of antibody materials are cholera TP0821 antibody and cholera TP0319 antibody and suddenly respectively Random TP0624 antibody and cholera O139 tropina antibody, its material of described working electrode is gold material or thermal decomposition is led Electricity macromolecule material, its pattern of described working electrode presents lamellar or thread, it is important that, its material of this substrate is poly dimethyl silicon Oxygen 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 The surface of the primary form of this material of surface chemical modification or any surface chemical modification, the structure of this device also includes elastic force Folder, two of this elastic clip clamping limb snap-in location in opposite directions, in the position of the neighbouring described terminal of this micro-fluidic chip, at least exists Attach on one of them described clamping limb to fix and be equiped with miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission electricity Cable, one end of this higher-order of oscillation electric signal transmission cable links together with this miniature ultrasonic transducer units；This elastic clip provides One facilitates the function that this device is disassembled；Its major function of this miniature ultrasonic transducer units is to test at the actual sample introduction of micro-fluidic chip Time, utilize its ultrasound wave launched to open to reduce the interface between the inwall of sample solution and this its inner passage of micro-fluidic chip Power so that it is can be compatible, and, utilize described sample introduction end and described terminal and this miniature ultrasonic transducer units installation position it Between distance difference and difference on its ultrasonic intensity experienced, its interfacial tension of sample introduction end and institute described in induced synthesis Stating the difference between its interfacial tension of terminal, the interfacial tension difference between these two ends of this micro-fluidic chip can be at this micro-fluidic chip These two ends between formed pressure gap, this pressure gap can drive sample solution to described end flow；This miniature ultrasonic changes Can its function of device also include with its ultrasound wave launched check in sample contained biomacromolecule its at this micro-fluidic chip Absorption on its inner passage inner surface, and then check its body of substrate of this polydimethylsiloxane material relative to this biomacromolecule The effect of swallowing up；Soft and this polydimethylsiloxane material of having elasticity its function of substrate includes with its suction strong to ultrasound wave The character received, absorbs strongly to ultrasound wave, and thereby limited between this terminal of this micro-fluidic chip to this sample introduction end The rapid decrement of ultrasonic intensity is realized within short distance；And, Micropump, this Micropump is connected with this sample introduction end；The merit of this Micropump Can be that the interfacial tension between the inwall of this sample solution and this its inner passage of micro-fluidic chip is dropped by this ul-trasonic irradiation Under the precondition that the compatibility low, alternate increases, pump strength with the mechanicalness of this Micropump and come and described the two of the induction of this ultrasound wave Its driving force brought of interfacial tension difference between end 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 direction flowing.

Described miniature ultrasonic transducer units can certainly be all installed on two clamping limbs；But, only installing one is miniature Ultrasonic transducer is the most enough dealt with and is employed.

Itself art-recognized meanings of elastic clip one word is known.

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 chitosan gold size solution and cholera specific antibody solution to be sufficiently mixed uniformly, uses point sample instrument Point sample or coat specified structure position, and make its drying and forming-film form.Cholera specific antibody in described gold size sensitive membrane is equal For the cholera antibody of horseradish peroxidase or glucose oxidase labelling, described gold size sensitive membrane be included as fixing above-mentioned respectively Cholera specific antibody and introduce complementary medium therein, described complementary medium such as chitosan, cellulose acetate, gelatin 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 device can also include higher-order of oscillation electric signal generator；It is another for described higher-order of oscillation electric signal transmission cable One end 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 5 milliwatts and 5000 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 four-way micro-fluidic chip with described Dual Drive coupling operating mode, Four-way electrochemical analytical instrument is utilized respectively four kinds of cholera diagnostic antigens to be detected.

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

1, adding blood serum sample liquid in micro-pipeline, under described Dual Drive coupling operating mode drives, various cholera antigens divide Son is by the cholera specific antibody of the corresponding horseradish peroxidase-labeled of gold size sensitive membrane embedding on electrode surface in each passage Capture.

2, the cholera specific antibody of horseradish peroxidase-labeled forms immune complex with the cholera antigen in blood serum sample.

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, cholera antigen is carried out comprehensive diagnos.

It is an advantage of the invention that at elastic clip described in its close position snap-in location of described terminal of described micro-fluidic chip, with Being attached the miniature ultrasonic transducer units installed on the clamping limb of this elastic clip, it is launched to utilize this miniature ultrasonic transducer units Low-power, the ultrasound wave of high-frequency band so that without this most hydrophobic micro-fluidic chip internal pipeline of surface chemical modification The compatibility between its tube wall and test object water solution is significantly increased, and what this was sample liquid stream is possible by providing a reality Property；Meanwhile, its strong absorbability to ultrasound wave of polydimethylsiloxane substrate is utilized, in comparatively short distance, the most just It is, in the shortest distance of the only several centimeters yardstick from described terminal to described sample introduction end, to reach the quick of ultrasonic intensity Successively decreasing, thereby the difference of described interfacial tension is caused at the described two ends at this micro-fluidic chip, the interfacial tension between these two ends Difference can cause a kind of driving force, and its function of driving force that this kind causes because of interfacial tension difference is to drive sample liquid stream to exist Flow to described terminal direction in the most hydrophobic capillary channel；And simultaneous described Micropump in structure, its function It is that the interfacial tension between the inwall of this sample solution and this its inner passage of micro-fluidic chip is dropped by this ul-trasonic irradiation Under the precondition that the compatibility low, alternate increases, pump strength with the mechanicalness of this Micropump and come and described the two of the induction of this ultrasound wave Its driving force brought of interfacial tension difference between end 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 direction flowing；The existence of this Micropump so that this miniature ultrasonic Its ultrasonic emitting intensity of wave transducer can be allowed to appropriateness reduction, and this is for containing ultrasound wave sensitive composition in detection object Situation is particularly suitable for；And due to this ultrasonic transducer and the existence of radiated ultrasound wave thereof, it is possible to increase the alternate compatibility, fall Low interfacial tension, and provide this two ends interfacial tension difference its special driving force brought, then, in this case, Its flow resistance in this micro-channel of sample liquid stream is greatly reduced, and correspondingly, its running resistance of this Micropump is greatly reduced, so, This Micropump just can be to carry out the pumping work for described sample solution than relatively low pumping pressure, due to mechanical pumping Pressure is greatly reduced, and therefore, in such a situation, is just not susceptible to cause because sample introduction terminal tool pumping pressure is excessive Described sample introduction end and the described micro-channel bubbling of near zone thereof, expand, deform, distort and between this region substrate and cover plate Stripping etc. problem；This Dual Drive of this case couples the scheme of running and adds the manipulation for this sample fluid flow action Property, it is possible to allow to use ultrasonic intensity, ultrasonic frequency, Micropump pump power, Micropump pumping pressure etc. multiple indexs Flow rate, flowing action for this flowing include that flow forward or time-out flowing or acceleration flowing etc. flowing action carry out many Parameter accurately manipulates；By the scheme of this Dual Drive of this case coupling running, entirely without must be to the base of this polydimethylsiloxane material Its micro-channel of sheet etc. relevant surfaces carries out any surface chemical modification or surface chemical modification, has altogether dispensed with this surface chemistry Modify or the laborious procedures of surface chemical modification；On the other hand, the ultrasound wave of this low-power, high-frequency band, additionally it is possible to containment examination The absorption on this literalness naked its inner surface of pipeline of polydimethylsiloxane substrate of the biomacromolecule in sample, and then containment The effect of swallowing up of this polydimethylsiloxane substrate the most described biomacromolecule of its body；Described antigen, antibody and antigen are with anti- The Reversible binding thing of body is the most all belonging to the type of described biomacromolecule；Due to described adsorption and described gulping down No effect is not contained effectively, and therefore, dependence test result will be better able to reflect practical situation objectively；This low-power, height Again and again the effect of section ultrasound wave, the most also includes facilitating what the Reversible binding between antigen, antibody reacted quickly to reach, and this makes Dependence test operation 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.

Fix on its clamping limb of this elastic clip in this case structure and installed described miniature ultrasonic transducer units, this architecture provides One facilitates the function that this device is disassembled, and so, this elastic clip just can facilitate together with miniature ultrasonic transducer units appended on it Ground is mutually disengaged with this micro-fluidic chip, then, the component that this part can freely depart from just can be reused perhaps with circulating benignly Repeatedly；This architectural feature is conducive to saving the use cost of this device.

Accompanying drawing explanation

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

In figure, 1 is elastic clip, and 2,7 is two clamping limbs of elastic clip respectively, and 3 is the described terminal of this micro-fluidic chip, 4 is the described sample introduction end of this micro-fluidic chip, and 5 is the substrate of polydimethylsiloxane material, and 6 is cover plate, and 8 is miniature super Acoustic wave transducer, 9 is higher-order of oscillation electric signal transmission cable, and 10 is tension spring, and 11 is infusion tube, and 12 is Micropump； This spring clamp structure in legend is only the legend structure of signal, and actual spring clamp structure is not limited to this legend spring clamp structure；Figure Arrow in example indicate this micro-fluidic chip its when actual motion, driven by pressure at two ends difference, the flowing of its sample liquid stream Direction.

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 5 together and cover plate 6, and described substrate 5 and cover plate 6 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 6 of this substrate 5 It is jointly mounted to this substrate 5 together mutually and is jointly built into the micro-fluidic chip containing pipeline configuration with this cover plate 6, this pipeline Locations of structures be positioned at the juncture area that this substrate 5 is bonded to each other with this cover plate 6, the two ends of this pipeline respectively with this micro-fluidic core Sample introduction end 4 and the terminal 3 of sheet connect, and this sample introduction end 4 is the injection end of this micro-fluidic chip sample solution, and this terminal 3 is The terminal of sample solution flowing in its chip during the test of this micro-fluidic chip actual sample introduction, this terminal 3 is the most remote with this sample introduction end 4 From, the distance between this terminal 3 and this sample introduction end 4 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 On conductive electrodes embedded cholera specific antibody gold size sensitive membrane constitute, the structure of this pipeline is parallel construction, described in The pipeline of parallel construction is made up of four lateral parallel connections, and the quantity of described working electrode is four, these four working electrodes Installation position lays respectively in described four laterals, and, in its top layer gold size sensitive membrane structure of these four working electrodes Specific antibody is four kinds of cholera antibody materials that can be specific binding to cholera antigen respectively, and these four kinds of antibody materials are suddenly respectively Random TP0821 antibody and cholera TP0319 antibody and cholera TP0624 antibody and cholera O139 tropina antibody, Its material of described working electrode be gold material or thermal decomposition conducting polymer material, its pattern of described working electrode present lamellar or Thread, it is important that, this its material of substrate 5 is polydimethylsiloxane material, and this its surface of substrate 5 is the surface of primary form, The surface of this primary form its be intended to refer to not through this material of any surface chemical modification or any surface chemical modification The surface of primary form, the structure of this device also includes elastic clip 1, two of this elastic clip 1 clamping limb 2,7 in opposite directions Snap-in location attaches solid on the position of the neighbouring described terminal 3 of this micro-fluidic chip, a described clamping limb at least in Surely being equiped with in miniature ultrasonic transducer units, this example, this miniature ultrasonic transducer units 8 is fixed on clamping limb 7 by attaching, with And, higher-order of oscillation electric signal transmission cable 9, one end of this higher-order of oscillation electric signal transmission cable 9 and this miniature ultrasonic transducing Device 8 links together；Can also fix the most respectively on two clamping limbs 2,7 and install miniature ultrasonic transducer units, but one For as, only installing miniature ultrasonic transducer units on a clamping limb and just be enough to deal with use needs, this elastic clip 1 provides One facilitates the function that this device is disassembled；This its major function of miniature ultrasonic transducer units 8 is to survey at the actual sample introduction of micro-fluidic chip During examination, utilize its ultrasound wave launched to reduce the interface between the inwall of sample solution and this its inner passage of micro-fluidic chip Tension force so that it is can be compatible, and, utilize described sample introduction end 4 and described terminal 3 and this miniature ultrasonic transducer units 8 Distance difference between installation position and the difference on its ultrasonic intensity experienced, sample introduction end 4 described in induced synthesis its Difference between interfacial tension and its interfacial tension of described terminal 3, the interfacial tension between these two ends 3,4 of this micro-fluidic chip Difference can form pressure gap between these two ends 3,4 of this micro-fluidic chip, and this pressure gap can drive sample solution to institute State the flowing of terminal 3 direction；This its function of miniature ultrasonic transducer units 8 also includes checking institute in sample with its ultrasound wave launched Its absorption on its inner passage inner surface of this micro-fluidic chip of the biomacromolecule contained, and then check this polydimethylsiloxanes Its body of substrate 5 of alkane material is relative to the effect of swallowing up of this biomacromolecule；Softness also has this elastic polydimethylsiloxane material Its function of substrate 5 include, with the character of its absorption strong to ultrasound wave, ultrasound wave being absorbed strongly, and thereby micro-at this This terminal 3 of fluidic chip is to the rapid decrement realizing ultrasonic intensity within the limited short distance between this sample introduction end 4；And, Micropump 12, this Micropump 12 is connected with this sample introduction end 4；The function of this Micropump 12 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, poor with the interfacial tension that the mechanicalness pumping strength of this Micropump 12 is come between the described two ends 3,4 of this ultrasound wave induction Its driving force brought different is supported mutually, adjusts mutually, is mutually coupled, and pools one and drive in the way of Collaboration Test liquid flows to the strength of described terminal 3 direction flowing.

Arrow in legend indicate this micro-fluidic chip its when actual motion, driven by two ends 3,4 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.

Described Micropump 12 can customize to specialized factory.

Involved elastic clip 1 is commercially available.Be available for this case structure use commercially available alternative spring clamp structure and moulding and Size etc., quality is various, and concrete elastic clip pattern can be selected as required.

Involved miniature ultrasonic transducer units 8 is commercially available；Can also customize to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal transmission cable 9 is commercially available；Can also be to ultrasonic transducer producer or cable special manufacturer Family's customization.

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

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. driving component is easily-disassembled and cholera diagnosis device more capable of circulation, and the structure of this 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, and described substrate and cover plate are plate Shape thing or tablet, the conduit knot 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 been built into the micro-fluidic chip containing pipeline configuration jointly, this pipe The locations of structures in road 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 chip Sample introduction end and terminal connect, this sample introduction end is the injection end of this micro-fluidic chip sample solution, and this terminal is this micro-fluidic core Sheet 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 with this Distance between sample introduction end, between 3 centimetres and 10 centimetres, is sequentially equiped with working electrode in this pipeline on diverse location 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 cholera specific antibody is constituted, and the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is by four Bar lateral parallel connection is constituted, and the quantity of described working electrode is four, and the installation position of these four working electrodes lays respectively at institute State in four laterals, and, the specific antibody in its top layer gold size sensitive membrane structure of these four working electrodes is right respectively Cholera antigen can specific binding four kinds of cholera antibody materials, these four kinds of antibody materials be respectively cholera TP0821 antibody and Cholera TP0319 antibody and cholera TP0624 antibody and cholera O139 tropina antibody, its material of described working electrode Matter is gold material or thermal decomposition conducting polymer material, and its pattern of described working electrode presents lamellar or thread, it is characterised in that Its material of this substrate is polydimethylsiloxane material, and its surface of this substrate is the surface of primary form, the surface of this primary form It is intended to refer to not through the surface of primary form of this material of any surface chemical modification or any surface chemical modification, The structure of this device also includes elastic clip, neighbouring at this micro-fluidic chip of two of this elastic clip clamping limb snap-in location in opposite directions The position of described terminal, on a described clamping limb at least in, attaching is fixing is equiped with miniature ultrasonic transducer units, and, Higher-order of oscillation electric signal transmission cable, one end of this higher-order of oscillation electric signal transmission cable is connected to this miniature ultrasonic transducer units Together；This elastic clip provides a function facilitating this device to disassemble；Its major function of this miniature ultrasonic transducer units is micro- During the test of fluidic chip actual sample introduction, it is internal logical to reduce sample solution and this micro-fluidic chip to utilize its ultrasound wave launched Interfacial tension between the inwall in road so that it is can be compatible, and, utilize described sample introduction end and described terminal and this miniature super Distance difference between acoustic wave transducer installation position and the difference on its ultrasonic intensity experienced, described in induced synthesis Difference between its interfacial tension of sample introduction end and its interfacial tension of described terminal, the interfacial tension between these two ends of this micro-fluidic chip Difference can form pressure gap between these two ends of this micro-fluidic chip, and this pressure gap can drive sample solution to described terminal Flowing；Its function of this miniature ultrasonic transducer units also includes checking contained in sample biological big point with its ultrasound wave launched Son its absorption on its inner passage inner surface of this micro-fluidic chip, and then check this polydimethylsiloxane material substrate its Body is relative to the effect of swallowing up of this biomacromolecule；Soft and this polydimethylsiloxane material of having elasticity its function of substrate includes With the character of its absorption strong to ultrasound wave, ultrasound wave is absorbed strongly, and thereby this terminal of this micro-fluidic chip to should The rapid decrement of ultrasonic intensity is realized within limited short distance between sample introduction end；And, Micropump, this Micropump and this sample introduction End connects；The function of this Micropump is, the interfacial tension between the inwall of this sample solution and this its inner passage of micro-fluidic chip Reduced by this ul-trasonic irradiation, under precondition that the alternate compatibility increases, with the mechanicalness of this Micropump pump strength come with should Its driving force brought of interfacial tension difference between the described two ends of ultrasound wave induction is supported mutually, is adjusted mutually, mutually Coupling, pools one in the way of Collaboration and drives test liquid to flow to the strength of described terminal direction flowing.

Driving component the most according to claim 1 is easily-disassembled and cholera diagnosis device more capable of circulation, and its feature exists In, described pipeline includes that described lateral is capillary channel.

Driving component the most according to claim 1 is easily-disassembled and cholera diagnosis device more capable of circulation, and its feature exists In, described thermal decomposition conducting polymer is the conductive material formed after anoxybiotic heat treatment by polyimides or polyacrylonitrile.

Driving component the most according to claim 1 is easily-disassembled and cholera diagnosis device more capable of circulation, and its feature exists In, the width of described working electrode or diameter between 0.1 micron to 2000 micron, and, the length of described working electrode Spend between 1 micron to 15000 micron.

Driving component the most according to claim 1 is easily-disassembled and cholera diagnosis device more capable of circulation, and its feature exists In, the thickness of described gold size sensitive membrane is between 10 nanometers and 200 nanometers.

Driving component the most according to claim 1 is easily-disassembled and cholera diagnosis device more capable of circulation, and its feature exists In, its material of described cover plate in structure is polydimethylsiloxane material.

Driving component the most according to claim 1 is easily-disassembled and cholera diagnosis device more capable of circulation, and its feature exists In, described Micropump is miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.

Driving component the most according to claim 1 is easily-disassembled and cholera diagnosis device more capable of circulation, and its feature exists In, described cover plate in structure and its thickness of substrate are all between 1.0 millimeters and 5.0 millimeters.

Driving component the most according to claim 1 is easily-disassembled and cholera diagnosis device more capable of circulation, and its feature exists Also include higher-order of oscillation electric signal generator in, the structure of this device, the described higher-order of oscillation its other end of electric signal transmission cable with This higher-order of oscillation electric signal generator connects.

Driving component the most according to claim 1 is easily-disassembled and cholera diagnosis device more capable of circulation, and its feature exists In, its specified ultrasonic emitting power of this miniature ultrasonic transducer units between 5 milliwatts and 5000 milliwatts, this miniature ultrasonic The frequency of its ultrasound wave operationally launched of wave transducer is between 100KHz and 12MHz.