CN107138184A

CN107138184A - Driving is with the easily-disassembled and recyclable cholera diagnosis device of component

Info

Publication number: CN107138184A
Application number: CN201610137421.8A
Authority: CN
Inventors: 李榕生
Original assignee: Individual
Current assignee: Individual
Priority date: 2016-03-01
Filing date: 2016-03-01
Publication date: 2017-09-08

Abstract

The present invention relates to a kind of driving with the easily-disassembled and recyclable cholera diagnosis device of component, belong to analysis testing field.There is serial problem with dimethyl silicone polymer i.e. PDMS that is cheap and easily processing to make the substrate of cholera diagnosis micro-fluidic chip；This case is directed to the serial problem.This case main points are, the selected PDMS with ecosystem surface of substrate, and the elastic clip of miniature ultrasonic transducer units will be attached on its clamping limb with elastic force snap-in location in its neighbor positions of the test liquid stream terminal of the micro-fluidic chip, simultaneously, ultrasonic wave damper is installed at the sample introduction end of the micro-fluidic chip, reach ultrasonic intensity rapid decrement in short distance, so as to form interfacial tension difference at the two ends of the chip, difference offer is a kind of to drive the strength that test liquid stream flows along hydrophobic capillary channel to the terminal direction, the strength with Micropump its mechanicalness pumping strength for being included in structure while intercouple, Collaboration.

Description

Driving is with the easily-disassembled and recyclable cholera diagnosis device of component

Technical field

The present invention relates to a kind of driving with the easily-disassembled and recyclable cholera diagnosis device of component, the device is to be based on antigen The reaction of/antibody specificity carrys out the special purpose device of cholera diagnosis antigen, belongs to analysis testing field.

Background technology

The micro-fluidic cholera diagnostic techniques background of associated multi-channel, may refer to the grade applications for a patent for invention of CN 200910150930.4 Case.

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

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

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

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

But, thing is really not so simple.

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

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

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

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

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

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

, can be from containment PDMS surfaces to life in order to prevent this PDMS substrate bodies relative to the effect of swallowing up of large biological molecule The absorption of thing macromolecular is addressed, and method is chemically modified modification aiming at the PDMS material surface, for For PDMS is the situation of substrate material, modification exactly is chemically modified to the surface of described micro-channel part, by changing The micro-channel inner surface of modification is learned, its absorption to large biological molecule can be contained, and then avoid large biological molecule quilt PDMS substrate body phases are swallowed up；But, or that old problem, that is, the chemical modification on PDMS material surface changes Surface state after property can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface automatically, The process of migration, soon can become that micro-channel inner surface state being modified by surface chemical modification again script strong and dredge Water and the state of strong adsorption large biological molecule, in other words, no matter how professionals in the field turn from side to side, the PDMS Its micro-channel inner surface of substrate is always rapidly to strong hydrophobic surface state evolution.

So, how can either obtain that PDMS material price is extremely cheap, substrate makes extremely easy benefit, can reach again Growth stage contains absorption process of the PDMS substrate micro-channel inner surfaces to large biological molecule, and then prevents PDMS substrate body phases The effect of swallowing up to large biological molecule so that related chip manufactured goods are able to maintain that a prolonged enough, rational shelf-life, It is exactly a very intractable problem.The problem makes the numerous specialties in this area as another problem addressed above, equally Personnel are entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise.The hardly possible Also be present many year in topic, so far, also not yet properly settled.

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

The content of the invention

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

The present invention solves the technical problem by following scheme, and the device that the program is provided is that a kind of driving component is easily-disassembled And recyclable cholera diagnosis device, the structure of the device includes multichannel micro-fluidic chip, the knot of the micro-fluidic chip Structure includes installing substrate and cover plate together bonded to each other, and the substrate and cover plate are plate object or tablet, the substrate Contain the channel structure via mould pressing process or etching technics formation towards that face of the cover plate, it is bonded to each other to be installed together The substrate and the cover plate have been built into the micro-fluidic chip containing pipeline configuration jointly, the locations of structures of the pipeline be located at the substrate with Cover plate juncture area bonded to each other, the two ends of the pipeline are connected with the sample introduction end of the micro-fluidic chip and terminal respectively, should Sample introduction end is the injection end of the micro-fluidic chip sample solution, when the terminal is the micro-fluidic chip actual sample introduction test in its chip The terminal of sample solution flowing, the terminal is located remotely from each other with the sample introduction end, and the distance between the terminal and the sample introduction end are between 3 lis Between rice and 10 centimetres, working electrode is sequentially equiped with diverse location in the pipeline and to electrode and reference electrode, The working electrode is quick by conductive electrode and the gold size for having embedded cholera specific antibody being attached on the conductive electrode Feel film to constitute, the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of four lateral parallel connections, institute The quantity for stating working electrode is four, and the installation position of four working electrodes is located in four laterals respectively, and, Specific antibody in the sensitive membrane structure of its top layer gold size of four working electrodes can be specifically bound to cholera antigen respectively Four kinds of cholera antibody materials, four kinds of antibody materials are cholera TP0821 antibody and cholera TP0319 antibody and suddenly respectively Random TP0624 antibody and cholera O139 mycoprotein antibody, its material of the working electrode are that gold material or thermal decomposition are led Sheet or thread is presented in electric macromolecule material, its pattern of the working electrode, and emphasis is that its material of the substrate is poly dimethyl silicon Oxygen alkane material, its surface of the substrate is the surface of primary form, the surface of the primary form its be intended to refer to not by any The surface of the primary form of surface chemical modification or the material of any surface chemical modification, the structure of the device also includes elastic force Folder, two opposite clamping limb snap-in locations of the elastic clip at least exist in the position of the neighbouring terminal of the micro-fluidic chip Fixation is attached on one of those described clamping limb and is equiped with miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission electricity Cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable link together；The elastic clip is provided One facilitates the function that the device is disassembled；Its major function of the miniature ultrasonic transducer units is in the actual sample introduction test of micro-fluidic chip When, the ultrasonic wave launched using it is opened to reduce the interface between sample solution and the inwall of its inner passage of micro-fluidic chip Power, can be compatible, also, using the sample introduction end and the terminal and the miniature ultrasonic transducer units installation position it Between distance difference and the difference on its ultrasonic intensity experienced, its interfacial tension of sample introduction end and institute described in induced synthesis The interfacial tension difference stated between the difference between terminal its interfacial tension, the micro-fluidic chip two ends can be in the micro-fluidic chip The two ends between form pressure gap, the pressure gap can drive sample solution to the end flow；The miniature ultrasonic is changed Can device its function also include with its ultrasonic wave launched check large biological molecule contained in sample its in the micro-fluidic chip Absorption on its inner passage inner surface, and then check the substrate of the dimethyl silicone polymer material its body phase to the large biological molecule The effect of swallowing up；Softness simultaneously has its function of the substrate of the dimethyl silicone polymer material of elasticity including with its suction strong to ultrasonic wave The property of receipts, is absorbed strongly to ultrasonic wave, and thereby in the micro-fluidic chip terminal to limited between the sample introduction end The rapid decrement of ultrasonic intensity is realized within short distance；And, Micropump, the Micropump is connected with the sample introduction end；The work(of the Micropump Can be that the interfacial tension between the inwall of the sample solution and its inner passage of micro-fluidic chip is dropped by the ul-trasonic irradiation Under low, the alternate increased precondition of compatibility, described two induced with the ultrasonic wave are come with the mechanicalness pumping strength of the Micropump Interfacial tension difference its driving force brought between end is supported mutually, adjusts mutually, is mutually coupled, with Collaboration Mode pools the strength that one driving test liquid flows to the terminal direction flowing；Described its thickness of cover plate and substrate between Between 1.0 millimeters and 5.0 millimeters；And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or rod Shape；Its material of the ultrasonic wave damper is microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, another elastic force Folder, another elastic clip with its gripping strength by the sample introduction end of the micro-fluidic chip and the ultrasonic wave damper it is bonded to each other press from both sides Together, the strong consumption to ultrasonic energy that the ultrasonic wave damper is brought with its material, is further supported at this The micro-fluidic chip terminal is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end, and thereby Further expand the difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension.

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

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

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

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

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

The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and cholera specific antibody solution uniformly, uses point sample instrument Point sample is coated on specified structure position, and forms its drying and forming-film.Cholera specific antibody in the gold size sensitive membrane is equal The cholera antibody marked for horseradish peroxidase or glucose oxidase, the gold size sensitive membrane has been included as fixing above-mentioned each Cholera specific antibody and introduce complementary medium therein, the complementary medium such as chitosan, cellulose acetate, gelatin Therein a kind of or their mixture.

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

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

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

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

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

Only with regard to naked PDMS substrates itself micro-channel molding or lithographic technique for, be open-and-shut known technology.

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

The structure of the device can also include higher-order of oscillation electric signal generator；Its is another for the higher-order of oscillation electric signal transmission cable One end can be connected with the higher-order of oscillation electric signal generator.

The involved higher-order of oscillation electric signal generator technology of itself, for the professional in ultrasonic technology field, be It is simple and known；The higher-order of oscillation electric signal generator can be customized to ultrasonic instrument specialized factory.

The preferred scope of its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units be between 5 milliwatts and 5000 milliwatts it Between；The preferred scope of the frequency of its ultrasonic wave operationally launched of the miniature ultrasonic transducer units be between 100KHz with Between 12MHz.

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

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

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

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

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

Described its size of ultrasonic wave damper is not limited, and described its length of ultrasonic wave damper, width, thickness may each be according to need The arbitrary size to be set.

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

The microcellular rubber is commercially available.

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

The sponge rubber is commercially available.

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

The polyurethane micropore elastomer material is commercially available.

The microcellular rubber preferred microporous silicon rubber or micropore fluorubber.

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

The microporous silicon Rubber market is on sale.

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

The micropore fluorubber is commercially available.

Another described elastic clip, naturally also elastic clip；The word of elastic clip one art-recognized meanings of itself are known.

Various elastic clip market is all on sale.

The application method of this case micro-fluidic chip：

This case is flowed with dual drive coupling operating mode driving liquid stream in the capillary channel of the four-way micro-fluidic chip, Four kinds of cholera diagnostic antigens are detected respectively using four-way electrochemical analytical instrument.

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

1st, blood serum sample liquid is added in micro-pipe road, under dual drive coupling operating mode driving, various cholera antigens point The cholera specific antibody for the corresponding horseradish peroxidase-labeled that son is embedded by gold size sensitive membrane on electrode surface in each passage Capture.

2nd, the cholera antigen formation immune complex in the cholera specific antibody and blood serum sample of horseradish peroxidase-labeled.

3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, using the above-mentioned reaction of amperometric detection Caused curent change, is derived from the species and content of various analytes.

4th, result is subjected to comprehensive analysis, comprehensive diagnos is carried out to cholera antigen.

It is an advantage of the invention that in elastic clip described in the terminal of the micro-fluidic chip its close position snap-in location, with The miniature ultrasonic transducer units installed are attached on the clamping limb of the elastic clip, it is launched using the miniature ultrasonic transducer units The ultrasonic wave of low-power, high-frequency band so that without strong hydrophobic micro-fluidic chip internal pipeline of surface chemical modification Compatibility between its tube wall and the test object aqueous solution is significantly increased, and this passes through possible there is provided a reality for test liquid stream Property；Meanwhile, using its strong absorbability to ultrasonic wave of dimethyl silicone polymer substrate, in shorter distance, also Be, from the terminal to the very short distance of only several centimeters yardsticks the sample introduction end in, reach the quick of ultrasonic intensity Successively decrease, interfacial tension between the difference of the interfacial tension, the two ends is thereby caused at the two ends of the micro-fluidic chip Difference can cause a kind of driving force, this kind because caused by interfacial tension difference its function of driving force be to drive test liquid stream to exist Originally flowed in strong hydrophobic capillary channel to the terminal direction；And the simultaneous Micropump in structure, its function It is that the interfacial tension between the inwall of the sample solution and its inner passage of micro-fluidic chip is dropped by the ul-trasonic irradiation Under low, the alternate increased precondition of compatibility, described two induced with the ultrasonic wave are come with the mechanicalness pumping strength of the Micropump Interfacial tension difference its driving force brought between end is supported mutually, adjusts mutually, is mutually coupled, with Collaboration Mode pools the strength that one driving test liquid flows to the terminal direction flowing；The presence of the Micropump so that the miniature ultrasonic Its ultrasonic wave emissive porwer of wave transducer can be allowed to appropriate reduction, and this in detection object for containing ultrasonic wave sensitive composition Situation is particularly suitable for；And by the presence of the ultrasonic transducer and its radiated ultrasonic wave, it is possible to increase alternate compatibility, drop Low interfacial tension, and the two ends interfacial tension difference special driving force that it is brought is provided, then, in this case, Its flow resistance in the micro-channel of test liquid stream is greatly reduced, and correspondingly, its running resistance of the Micropump is greatly reduced, so, The Micropump just can be to carry out the pumping work for the sample solution than relatively low pumping pressure, due to mechanical pumping Pressure is greatly reduced, therefore, in such a situation, be just not susceptible to because sample introduction terminal tool pumping pressure it is excessive caused by Between the micro-channel bubbling of the sample introduction end and its near zone, expansion, deformation, distortion and the region substrate and cover plate The problems such as stripping etc.；This case dual drive couples the scheme of running and adds the manipulation acted for the sample fluid flow Property, it can allow for coming using the multiple indexs of ultrasonic intensity, ultrasonic frequency, Micropump pump power, Micropump pumping pressure etc. Flow rate, flowing action for the flowing include flow forward or suspend flowing or accelerate flowing etc. flowing action progress many Parameter is accurately manipulated；By the scheme of this case dual drive coupling running, entirely without must be to the base of the dimethyl silicone polymer material Any surface chemical modification of its micro-channel of piece etc. relevant surfaces progress or surface chemical modification, have altogether dispensed with the surface chemistry Modification or the laborious procedures of surface chemical modification；On the other hand, the ultrasonic wave of the low-power, high-frequency band, additionally it is possible to containment examination The absorption of large biological molecule in sample on literalness naked its inner surface of pipeline of dimethyl silicone polymer substrate, and then contain The swallow up effect of its body phase of dimethyl silicone polymer substrate to the large biological molecule；The antigen, antibody and antigen are with resisting The Reversible binding thing of body is all the type for belonging to described large biological molecule certainly；Due to described suction-operated and described gulp down Do not act on and effectively being contained, therefore, dependence test result will be better able to objectively reflect actual conditions；The low-power, height The effect of frequent section ultrasonic wave, also include facilitating the Reversible binding between antigen, antibody react certainly quickly reaches, and this causes Dependence test operation can be with than the completion of faster speed.

As described above, the presence of the Micropump so that its ultrasonic wave emissive porwer of the miniature ultrasonic transducer units can be allowed to fit Degree reduction, then, the feature helps to protect its sensitive coating of the working electrode, is allowed to from ultrasound injury.

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

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

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

The technical scheme of this case has dissolved its application related one to dimethyl silicone polymer substrate addressed above totally Row technical barrier.Based on this case scheme, the polydimethyl siloxane material of this kind very cheap and easily processing and fabricating just has can Can in the micro-fluidic chip its prepare, production, using etc. field play bigger effect.

The miniature ultrasonic transducer units have been installed in fixation on the elastic clip its clamping limb in this case structure, this architecture provides One facilitates the function that the device is disassembled, in this way, the elastic clip just can facilitate together with miniature ultrasonic transducer units appended thereon Ground is mutually disengaged with the micro-fluidic chip, then, the component that the part can freely depart from is reused in which just can circulate benignly to be permitted Repeatedly；The architectural feature is conducive to saving the use cost of the device.

Brief description of the drawings

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

In figure, 1 is elastic clip, and 2,7 be two clamping limbs of elastic clip respectively, and 3 be the terminal of the micro-fluidic chip, 4 be the sample introduction end of the micro-fluidic chip, and 5 be the substrate of dimethyl silicone polymer material, and 6 be cover plate, and 8 be miniature super Acoustic wave transducer, 9 be higher-order of oscillation electric signal transmission cable, and 10 be tension spring, and 11 be infusion tube, and 12 be Micropump； The spring clamp structure in legend is only the legend structure of signal, and actual spring clamp structure is not limited to the legend spring clamp structure；Figure Example in arrow indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, the flowing of its test liquid stream Direction.The ultrasonic wave damper is depicted without in legend；Also another elastic clip is depicted without in legend.

Embodiment

In this case that Fig. 1 is shown embodiment, the structure of the device includes multichannel micro-fluidic chip, the micro-fluidic core The structure of piece includes the substrate 5 and cover plate 6 of installing bonded to each other together, and the substrate 5 and cover plate 6 are plate object or piece Contain the channel structure via mould pressing process or etching technics formation, phase in shape thing, that face towards the cover plate 6 of the substrate 5 The substrate 5 being mutually jointly mounted to together has been built into the micro-fluidic chip containing pipeline configuration jointly with the cover plate 6, the pipeline Locations of structures be located at the substrate 5 and the cover plate 6 juncture area bonded to each other, the two ends of the pipeline respectively with the micro-fluidic core The sample introduction end 4 of piece and terminal 3 are connected, and the sample introduction end 4 is the injection end of the micro-fluidic chip sample solution, and the terminal 3 is The terminal that sample solution flows in its chip when the actual sample introduction of the micro-fluidic chip is tested, the terminal 3 is mutually remote with the sample introduction end 4 From the distance between the terminal 3 and the sample introduction end 4 are between 3 centimetres and 10 centimetres, in the pipeline on diverse location Sequentially it is equiped with working electrode and to electrode and reference electrode, the working electrode is by conductive electrode and is attached to this and leads The gold size sensitive membrane for having embedded cholera specific antibody on conductive electrodes is constituted, and the construction of the pipeline is in parallel construction, described to be in The pipeline of parallel construction is made up of four lateral parallel connections, and the quantity of the working electrode is four, four working electrodes Installation position is located in four laterals respectively, and, in the sensitive membrane structure of its top layer gold size of four working electrodes Specific antibody is the four kinds of cholera antibody materials that can be specifically bound to cholera antigen respectively, and four kinds of antibody materials are suddenly respectively Random TP0821 antibody and cholera TP0319 antibody and cholera TP0624 antibody and cholera O139 mycoprotein antibody, Its material of the working electrode is gold material or thermal decomposition conducting polymer material, the working electrode its pattern present sheet or Thread, emphasis is, its material of the substrate 5 is dimethyl silicone polymer material, and its surface of substrate 5 is the surface of primary form, The surface of the primary form its be intended to refer to the material not no by any surface chemical modification or any surface chemical modification Primary form surface, the structure of the device also includes elastic clip 1, two opposite clamping limbs 2,7 of the elastic clip 1 Snap-in location attaches solid on the position of the neighbouring terminal 3 of the micro-fluidic chip a, clamping limb at least in Surely it is equiped with miniature ultrasonic transducer units, this example, the miniature ultrasonic transducer units 8 are fixed on clamping limb 7 by attaching, with And, higher-order of oscillation electric signal transmission cable 9, one end of the higher-order of oscillation electric signal transmission cable 9 and the miniature ultrasonic transducing Device 8 links together；It all can also respectively be fixed on two clamping limbs 2,7 and install miniature ultrasonic transducer units, but one As for, miniature ultrasonic transducer units are installed only on a clamping limb and are just enough to deal with using needs, the elastic clip 1 is provided One facilitates the function that the device is disassembled；Its major function of the miniature ultrasonic transducer units 8 is surveyed in the actual sample introduction of micro-fluidic chip During examination, the ultrasonic wave launched using it reduces the interface between sample solution and the inwall of its inner passage of micro-fluidic chip Tension force, can be compatible, also, utilizes the sample introduction end 4 and the terminal 3 and the miniature ultrasonic transducer units 8 Difference in the distance between installation position difference and its ultrasonic intensity experienced, sample introduction end 4 described in induced synthesis its Interfacial tension between difference between interfacial tension and the terminal 3 its interfacial tension, the micro-fluidic chip two ends 3,4 Difference can form pressure gap between the two ends 3,4 of the micro-fluidic chip, and the pressure gap can drive sample solution to institute State the flowing of the direction of terminal 3；Its function of the miniature ultrasonic transducer units 8 also includes checking institute in sample with its ultrasonic wave launched Its absorption on the micro-fluidic chip its inner passage inner surface of the large biological molecule contained, and then check the polydimethylsiloxanes Swallow up effect of its body phase of the substrate 5 of alkane material to the large biological molecule；The dimethyl silicone polymer material that is soft and having elasticity Substrate 5 its function include, with its property to the strong absorption of ultrasonic wave, ultrasonic wave being absorbed strongly, it is and thereby micro- at this The fluidic chip terminal 3 is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 4；And, Micropump 12, the Micropump 12 is connected with the sample introduction end 4；The function of the Micropump 12 is, in the sample solution and the micro-fluidic core Interfacial tension between the inwall of its inner passage of piece is reduced by the ul-trasonic irradiation, the increased precondition of alternate compatibility Under, it is poor with the interfacial tension that the mechanicalness pumping strength of the Micropump 12 is come between the two ends 3,4 of ultrasonic wave induction Its different driving force brought is supported mutually, adjusts mutually, is mutually coupled, and one driving is pooled in the way of Collaboration Test liquid flows to the strength of the direction of terminal 3 flowing；Its thickness of the cover plate 6 and substrate 5 is between 1.0 millimeters and 5.0 Between millimeter；And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；The ultrasonic wave disappears It is microcellular rubber, sponge rubber or microporous polyurethane elastomer to subtract device its material；And, another elastic clip, another bullet Power folder with its gripping strength by the sample introduction end 4 of the micro-fluidic chip and the ultrasonic wave damper it is bonded to each other clip together, this is super The strong consumption to ultrasonic energy that sound wave damper is brought with its material, further supporting should in the micro-fluidic chip Terminal 3 thereby further expands to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 4 Difference between its interfacial tension of big described its interfacial tension of sample introduction end 4 and the terminal 3.

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

Arrow in legend indicate the micro-fluidic chip its in actual motion, by two ends 3,4 pressure differentials drive, its try The flow direction of sample liquid stream.

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

The Micropump 12 can be customized to specialized factory.

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

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

Involved miniature ultrasonic transducer units 8 are commercially available；It can also be customized 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；It can also be customized to relevant manufacturers.

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

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

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

Claims

1. driving includes multichannel micro-fluidic with the easily-disassembled and recyclable cholera diagnosis device of component, the structure of the device Chip, the structure of the micro-fluidic chip includes the substrate and cover plate of installing bonded to each other together, and the substrate and cover plate are plate Contain the conduit knot via mould pressing process or etching technics formation in shape thing or tablet, that face towards the cover plate of the substrate Structure, substrate bonded to each other being installed together has been built into the micro-fluidic chip containing pipeline configuration jointly with the cover plate, the pipe The locations of structures in road is located at the substrate and cover plate juncture area bonded to each other, the two ends of the pipeline respectively with the micro-fluidic chip Sample introduction end and terminal connection, the sample introduction end is the injection end of the micro-fluidic chip sample solution, and the terminal is the micro-fluidic core The terminal that sample solution flows in its chip when the actual sample introduction of piece is tested, the terminal is located remotely from each other with the sample introduction end, and the terminal is with being somebody's turn to do The distance between sample introduction end is sequentially equiped with working electrode in the pipeline between 3 centimetres and 10 centimetres on diverse location And to electrode and reference electrode, the working electrode is by conductive electrode and the embedding being attached on the conductive electrode The gold size sensitive membrane of cholera specific antibody is constituted, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by four The parallel connection of bar lateral is constituted, and the quantity of the working electrode is four, and the installation position of four working electrodes is located at institute respectively State in four laterals, and, the specific antibody in the sensitive membrane structure of its top layer of four working electrodes gold size is respectively pair Four kinds of cholera antibody materials that cholera antigen can be specifically bound, four kinds of antibody materials be respectively cholera TP0821 antibody and Cholera TP0319 antibody and cholera TP0624 antibody and cholera O139 mycoprotein antibody, its material of the working electrode Matter is gold material or thermal decomposition conducting polymer material, and sheet or thread is presented in its pattern of the working electrode, it is characterised in that Its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, the surface of the primary form It is intended to refer to not by any surface chemical modification or the surface of the primary form of the material of any surface chemical modification, The structure of the device also includes elastic clip, and two opposite clamping limb snap-in locations of the elastic clip are in the neighbouring of the micro-fluidic chip Fixation is attached on the position of the terminal, a clamping limb at least in and is equiped with miniature ultrasonic transducer units, and, Higher-order of oscillation electric signal transmission cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable are connected to Together；The elastic clip facilitates the function that the device is disassembled there is provided one；Its major function of the miniature ultrasonic transducer units is micro- When the actual sample introduction of fluidic chip is tested, it is internal logical to reduce sample solution and the micro-fluidic chip for the ultrasonic wave launched using it Interfacial tension between the inwall in road, can be compatible, also, miniature super with this using the sample introduction end and the terminal Difference in the distance between acoustic wave transducer installation position difference and its ultrasonic intensity experienced, described in induced synthesis Interfacial tension between difference between its interfacial tension of sample introduction end and the terminal its interfacial tension, the micro-fluidic chip two ends Difference can form pressure gap between the two ends of the micro-fluidic chip, and the pressure gap can drive sample solution to the terminal Flowing；Its function of the miniature ultrasonic transducer units also includes checking big point of biology contained in sample with its ultrasonic wave launched Its absorption on the micro-fluidic chip its inner passage inner surface of son, so check the dimethyl silicone polymer material substrate its Swallow up effect of the body phase to the large biological molecule；It is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and include With its property to the strong absorption of ultrasonic wave, ultrasonic wave is absorbed strongly, and thereby the micro-fluidic chip terminal to should The rapid decrement of ultrasonic intensity is realized within limited short distance between sample introduction end；And, Micropump, the Micropump and the sample introduction End connection；The function of the Micropump is, the interfacial tension between the inwall of the sample solution and its inner passage of micro-fluidic chip Reduced, under the increased precondition of alternate compatibility, come and this with the mechanicalness pumping strength of the Micropump by the ul-trasonic irradiation Interfacial tension difference its driving force brought between the two ends of ultrasonic wave induction supports mutually, adjustment, mutually mutually Coupling, pools the strength that one driving test liquid flows to the terminal direction flowing in the way of Collaboration；The cover plate and Its thickness of substrate is between 1.0 millimeters and 5.0 millimeters；And, ultrasonic wave damper, its profile of the ultrasonic wave damper In block, tabular or bar-shaped；Its material of the ultrasonic wave damper is microcellular rubber, sponge rubber or microporous polyurethane elastomer； And, another elastic clip, another elastic clip is disappeared the sample introduction end of the micro-fluidic chip and the ultrasonic wave with its gripping strength Subtract device to clip together bonded to each otherly, the strong abatement to ultrasonic energy that the ultrasonic wave damper is brought with its material is made With further support realizes ultrasonic intensity within micro-fluidic chip terminal to the limited short distance between the sample introduction end Rapid decrement, and thereby further expand the difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension.

2. driving according to claim 1 is existed with the easily-disassembled and recyclable cholera diagnosis device of component, its feature In it is capillary channel that the pipeline, which includes the lateral,.

3. driving according to claim 1 is existed with the easily-disassembled and recyclable cholera diagnosis device of component, its feature In, the thermal decomposition conducting polymer be by polyimides or polyacrylonitrile be heat-treated through anoxybiotic after the conductive material that is formed.

4. driving according to claim 1 is existed with the easily-disassembled and recyclable cholera diagnosis device of component, its feature In, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the length of the working electrode Degree is between 1 micron to 15000 microns.

5. driving according to claim 1 is existed with the easily-disassembled and recyclable cholera diagnosis device of component, its feature In the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.

6. driving according to claim 1 is existed with the easily-disassembled and recyclable cholera diagnosis device of component, its feature In its material of the cover plate in structure is dimethyl silicone polymer material.

7. driving according to claim 1 is existed with the easily-disassembled and recyclable cholera diagnosis device of component, its feature In the Micropump is miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.

8. driving according to claim 1 is existed with the easily-disassembled and recyclable cholera diagnosis device of component, its feature In the microcellular rubber is micropore silicon rubber or micropore fluorubber.

9. driving according to claim 1 is existed with the easily-disassembled and recyclable cholera diagnosis device of component, its feature Also include higher-order of oscillation electric signal generator in the structure of, the device, its other end of the higher-order of oscillation electric signal transmission cable with The higher-order of oscillation electric signal generator is connected.

10. driving according to claim 1 is existed with the easily-disassembled and recyclable cholera diagnosis device of component, its feature In its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 5 milliwatts and 5000 milliwatts, the miniature ultrasonic The frequency of its ultrasonic wave operationally launched of wave transducer is between 100KHz and 12MHz.