CN106153956A - Its substrate of chip uses the cholera diagnosis micro fluidic device of strong hydrophobic material - Google Patents

Abstract

The present invention relates to its substrate of a kind of chip and use the cholera diagnosis micro fluidic device of strong hydrophobic material, belong to analysis field tests.The polydimethylsiloxane inexpensively and easily processed i.e. PDMS as make the substrate of cholera diagnosis micro-fluidic chip then exist series a difficult problem；Its surface of this PDMS material is the most hydrophobic, and surface modification or surface are modified targetedly, and its effect is difficult to persistently, and this case aims to solve the problem that this series relevant issues.This case is characterized by, the PDMS with ecosystem surface selected by substrate, and the hinge-type fixture being attached to miniature ultrasonic transducer units manually fastened sample its neighbor positions of liquid stream terminal being positioned at 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, thereby facilitate sample liquid stream to flow along the most hydrophobic capillary channel to this terminal direction.

Description

Its substrate of chip uses the cholera diagnosis micro fluidic device of strong hydrophobic material

Technical field

The present invention relates to its substrate of a kind of chip and use the cholera diagnosis micro fluidic device of strong hydrophobic material, belong to analysis test neck Territory.

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.

Summary of the invention

The technical problem to be solved is to provide a package solution, solves to address above totally Two difficult problems, and, this solution is applied to cholera diagnosis multichannel micro-fluidic chip field, is formed a kind of novel Multichannel micro-fluidic device is used in cholera diagnosis.

The present invention solves described technical problem by following scheme, and the device that the program provides is that a kind of its substrate of chip uses by force The cholera diagnosis micro fluidic device of hydrophobic material, the structure of this micro fluidic device includes multichannel micro-fluidic chip, and this is micro-fluidic The structure of chip includes bonded to each other being installed in substrate together and cover plate, and described substrate and cover plate are plate object or tablet, The channel structure formed via mould pressing process or etching technics is contained in that face towards this cover plate of this substrate, this substrate possibly together with It is connected with this channel structure and pierces the window knot formed via mould pressing process, etching technics or simple drilling technology of this substrate Structure, this substrate being installed together bonded to each other and this cover plate have been built into jointly containing pipeline configuration and the liquid pool that is attached thereto The micro-fluidic chip of structure, the locations of structures of this pipeline is positioned at the interface zone that this substrate is bonded to each other with this cover plate, this window its Side is blocked by this cover plate and opposite side is open, and the locations of structures of this window is exactly the locations of structures of described liquid pool, described liquid pool Quantity is three, and two its locations of structures of liquid pool therein are positioned at the sample introduction end of this micro-fluidic chip, its knot of a remaining liquid pool The terminal of its chip liquid flowing when structure position is positioned at the test of this micro-fluidic chip actual sample introduction, this terminal is mutual with this sample introduction end Away from, one end of this pipeline via be similarly positioned in the manifold shape turnout of this interface zone bonded to each other respectively be positioned at sample introduction end This Liang Ge liquid pool UNICOM, this remaining liquid pool connection of the other end of this pipeline and the described terminal being positioned at this micro-fluidic chip Logical, and, the working electrode that is sequentially respectively installed in this pipeline on diverse location and to electrode and reference electrode, described Working electrode is by conductive electrode and the gold size sensitive membrane having embedded cholera specific antigen that is attached on this conductive electrode Constituting, the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is made up of four lateral parallel connections, described work The quantity making electrode is four, and the installation position of these four working electrodes lays respectively in described four laterals, and, should Specific antigen in four its top layer gold size sensitive membrane structures of working electrode is can be specific binding to cholera antibody four respectively Kind of cholera antigenic substance, these four kinds of antigenic substances are cholera TP0821 antigen and cholera TP0319 antigen and cholera respectively TP0624 antigen and cholera O139 antigen, its material of described working electrode is gold material or thermal decomposition conducting polymer material Matter, its pattern of described working electrode presents lamellar or thread, it is important that, its material of this substrate is polydimethylsiloxane material, Its surface of this substrate is the surface of primary form, the surface of this primary form its be intended to refer to not repair through any surface chemistry The surface of the primary form of this material of decorations or any surface chemical modification, the structure of this device also includes hinge-type fixture, this conjunction Its appearance profile of page fixture likeness in form hinge, this hinge-type fixture is by two hinges being mutually hinged and runs through these two One of hinge fastening screw and one mate with this fastening screw and with this fastening turnbuckle be connected together for manual tightly Gu and the nut of hand break loose is constituted, two hinges of this hinge-type fixture are respectively mutually drawn close with its tip and clamp this micro-fluidic core Sheet, described tip is positioned in the locations of structures of neighbouring described terminal of this micro-fluidic chip, a described page at least in Attach on sheet to fix and be equiped with miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, this higher-order of oscillation telecommunication One end of number transmission cable links together with this miniature ultrasonic transducer units；This hinge-type fixture provides one and facilitates this device The function disassembled；Its major function of this miniature ultrasonic transducer units is when the actual sample introduction of micro-fluidic chip is tested, and utilizes it to be sent out The ultrasound wave penetrated is to reduce the interfacial tension between the inwall of sample solution and described pipeline so that it is can be compatible, and, utilize Distance difference between described sample introduction end and described terminal and this miniature ultrasonic transducer units installation position and its experienced Ultrasonic intensity on difference, difference between its interfacial tension of sample introduction end and its interfacial tension of described terminal described in induced synthesis Different, the interfacial tension difference between these two ends of this micro-fluidic chip can form pressure differential between these two ends of this micro-fluidic chip Different, this pressure gap can drive sample solution to described end flow；Its function of this miniature ultrasonic transducer units also includes with its institute The ultrasound wave launched checks its absorption on described inner surface of pipeline of biomacromolecule contained in sample, and then it is poly-to check this Its body of the substrate of dimethyl siloxane material is relative to the effect of swallowing up of this biomacromolecule；The base of described polydimethylsiloxane material Its function of sheet includes and cover plate and working electrode and electrode and reference electrode together build this micro-fluidic chip, and soft also have elasticity Its function of substrate of this polydimethylsiloxane material also include, with the character of its absorption strong to ultrasound wave, ultrasound wave being carried out Strong absorb, and it is strong thereby to realize ultrasound wave within limited short distance between this terminal of this micro-fluidic chip to this sample introduction end The rapid decrement of degree.

Described miniature ultrasonic transducer units can certainly be all installed in two described hinges；But, only installing one is micro- Type ultrasonic transducer is the most enough dealt with and is employed.

Itself art-recognized meanings of hinge one word is known.

Described gold size sensitive membrane is chitosan gold size solution and cholera specific antigen 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 antigen in described gold size sensitive membrane is equal For the cholera antigen of horseradish peroxidase or glucose oxidase labelling, described gold size sensitive membrane be included as fixing above-mentioned respectively Cholera specific antigen 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 and described lateral and described manifold shape turnout, its internal diameter chi Very little may each be arbitrarily selected size, but, for less with the consideration of the aspects such as liquid sample to be measured and reduction reagent loss, Described pipeline and described lateral and described manifold shape turnout the most all select the passage of capillary level, described capillary level Passage imply that the passage that the internal diameter of capillary tube on its internal diameter and ordinary meaning is suitable.Described its inner passage of capillary tube transversal Face shape can be arbitrary shape, described shape of cross section is the most circular, oval, square, rectangle, bar shaped, the most also Can be arbitrary to there is the linear of bending, and, the interior shape of described capillary tube along with the extension of pipeline, different parts Shape of cross section 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.

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

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；With Sample ground, the technology of hole-opening known simple technique especially on naked PDMS substrate.This is not launched superfluous words by this case.

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

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

Itself technology of involved higher-order of oscillation electric signal generator, for the professional in ultrasonic technology field, be Simple and known；Described higher-order of oscillation electric signal generator can customize to ultrasonic instrument specialized factory.

The preferred scope of its specified ultrasonic emitting power of this miniature ultrasonic transducer units be between 5 milliwatts and 9000 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.

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

Described cover plate and its thickness of substrate can allow the thickness being easy to assembling being arbitrarily set, it is recommended that thickness 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:

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

This interfacial tension difference formed between these two ends of this micro-fluidic chip that this case is caused with described ultrasound wave, drives liquid Stream flows in the capillary channel of this four-way micro-fluidic chip, utilizes four-way electrochemical analytical instrument respectively to four kinds of cholera Antibody is detected.

Detect corresponding four kinds of cholera antibody with four kinds of cholera antigens, detect corresponding four kinds of cholera with four kinds of cholera antibody Antigen, similarly, can cholera diagnosis；The principle of its foundation is, necessarily antigen, antibody deposit in cholera patient, And mutual Reversible binding, form reversible conjugate, therefore, detect antibody thereby cholera diagnosis with antigen, and with antibody Go to detect antigen cholera diagnosis, diagnostic purpose can be reached.Certainly, its corresponding electrode sensitive decorative layer of different means Technically and differ.

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

1, adding blood serum sample liquid in micro-pipeline, under described ultrasound wave drives, various cholera antibody molecules are by each passage The cholera specific antigen capture of the corresponding horseradish peroxidase-labeled of gold size sensitive membrane embedding on electrode surface.

2, the cholera specific antigen of horseradish peroxidase-labeled forms immune complex with the cholera antibody 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 antibody is carried out comprehensive diagnos.

It is an advantage of the invention that its close position of described terminal at described micro-fluidic chip positions described hinge-type fixture, with Attached the miniature ultrasonic transducer units installed in this its hinge of hinge-type fixture, utilized its low-power launched, high-frequency band Ultrasound wave so that without surface chemical modification or surface chemical modification this most hydrophobic micro-fluidic chip internal pipeline its The compatibility between 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, and then, utilize between these two ends Pressure gap between its these two ends formed of the difference of interfacial tension, drives sample liquid stream the most hydrophobic in such a Capillary channel in described terminal direction flow.By this case liquid stream drive scheme, entirely without must be to this polydimethylsiloxanes The substrate of alkane material and internal pipeline thereof carry out any surface chemical modification or chemical modification, have altogether dispensed with this surface chemistry and have repaiied Decorations or the laborious procedures of chemical modification；And altogether dispense with the equipment of traditional Micropump etc；On the other hand, this is low Power, the ultrasound wave of high-frequency band, additionally it is possible to the biomacromolecule in containment sample is at this literalness naked polydimethylsiloxanes Absorption on its inner surface of pipeline of alkyl sheet, and then contain this polydimethylsiloxane substrate the most described biomacromolecule of its body The effect of swallowing up；Described antigen, antibody and antigen are the most all belonging to described biomacromolecule with the Reversible binding thing of antibody Type；Owing to described adsorption and the described effect of swallowing up are contained effectively, therefore, dependence test result will more Practical situation can be reflected objectively；This low-power, the effect of high-frequency band ultrasound wave, the most also include facilitating antigen, antibody Between Reversible binding reaction quickly reach, this make dependence test operation can be to complete than speed faster.

Owing to being made without the surface chemical modification for this polydimethylsiloxane its relevant surfaces of substrate or chemical modification behaviour Making, therefore, this surface chemical modification layer or chemically modified layer not need to exist, then, this polydimethylsiloxane Its body phase interior polymeric thing molecule of substrate diffuses to the surface the most automatically, migrate it caused to described surface chemical modification layer or The damaging influence of chemically modified layer does not exists.

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, the most cheap polydimethyl siloxane material of this kind is the most likely at this micro-fluidic chip Prepare, produce, application etc. field plays bigger effect.

Fixing in this its hinge of hinge-type fixture in this case structure and installed described miniature ultrasonic transducer units, this structure provides One function facilitating this device to disassemble, so, this hinge-type fixture is together with miniature ultrasonic transducer units appended in its hinge Just can be mutually disengaged with this micro-fluidic chip easily, then, the component that this part can freely depart from just can circulate benignly ground Reuse many times；This architectural feature is conducive to saving the use cost of this device.

Accompanying drawing explanation

Fig. 1 is the schematic diagram of this device embodiment chip part of this case structure, it is shown that the depression angle of this example structure Under chip internal pipeline and each electrode and the configuration of each relevant liquid pool, this figure is not depicted described hinge-type fixture with And the miniature ultrasonic transducer units set up in hinge and other described adnexa.

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

In figure, 1,2,10 is the liquid pool that three installation positions are different respectively, and 3 is manifold shape turnout, 4,7,11,14 Being installation position difference respectively but four laterals forming UNICOM in parallel structure parallel with one another, 5 is to be installed in lateral 4 The interior working electrode that specific antigenic substance is cholera TP0821 antigen in its top layer gold size sensitive membrane structure, 6 is installing The work that specific antigenic substance is cholera TP0319 antigen electricity in its top layer gold size sensitive membrane structure in lateral 7 Pole, 12 be the specific antigenic substance in its top layer gold size sensitive membrane structure being installed in lateral 11 be cholera The working electrode of TP0624 antigen, 13 is the specificity in its top layer gold size sensitive membrane structure being installed in lateral 14 Antigenic substance is the working electrode of cholera O139 antigen, and 8 is to electrode, and 9 is reference electrode, and 15 is hinge-type fixture, 16 Indicating linkwork position, 17 is fastening screw, and 18 is higher-order of oscillation electric signal transmission cable, and 19 is miniature ultrasonic Transducer, 20,25 is two hinges that locations of structures is different respectively, and 21 is cover plate, and 22 is substrate, and 23 is sample introduction end, 24 is terminal, and 26 is nut；This hinge-type clamp structure in legend is only the legend structure of signal, actual this hinge-type folder Have its structure and be not limited to this legend hinge-type clamp structure；Arrow in legend indicate this micro-fluidic chip its at actual motion Time, driven by pressure at two ends difference, the flow direction of its sample liquid stream.

Detailed description of the invention

In this embodiment of this case that Fig. 1 and Fig. 2 is shown, the structure of this device includes multichannel micro-fluidic chip, and this is micro- The structure of fluidic chip includes bonded to each other being installed in substrate 22 together and cover plate 21, and described substrate 22 and cover plate 21 are Plate object or tablet, that face towards this cover plate 21 of this substrate 22 is contained and is formed via mould pressing process or etching technics Channel structure, this substrate 22 possibly together be connected with this channel structure and pierce this substrate via mould pressing process, etching technics Or the window structure that simply drilling technology is formed, this substrate 22 being installed together bonded to each other is built into jointly with this cover plate 21 Containing pipeline configuration and the micro-fluidic chip of liquid pool structure that is attached thereto, described liquid pool is liquid pool 1, liquid pool 2, liquid pool 10, the locations of structures of this pipeline is positioned at the interface zone that this substrate 22 is bonded to each other with this cover plate 21, and its side of this window is by this Cover plate 21 blocks and opposite side is open, and the locations of structures of this window is exactly the structure position of described liquid pool 1, liquid pool 2, liquid pool 10 Putting, the quantity of described liquid pool is three, and the i.e. liquid pool 1 of two liquid pools therein and its locations of structures of liquid pool 2 are positioned at this micro-fluidic core The sample introduction end 23 of sheet, a remaining liquid pool i.e. its locations of structures of liquid pool 10 be positioned at this micro-fluidic chip actual sample introduction test time its The terminal 24 of liquid flowing in chip, this terminal 24 is located remotely from each other with this sample introduction end 23, and one end of this pipeline is via same position In the manifold shape turnout 3 of this interface zone bonded to each other respectively be positioned at this liquid pool 1 and this liquid pool 2 UNICOM of sample introduction end 23, This remaining liquid pool i.e. liquid pool 10 UNICOM of the other end of this pipeline and the described terminal 24 being positioned at this micro-fluidic chip, with And, the working electrode that is sequentially respectively installed in this pipeline on diverse location and to electrode 8 and reference electrode 9, described work Make electrode by conductive electrode and the gold size sensitive membrane structure having embedded cholera specific antigen that is attached on this conductive electrode Becoming, the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is made up of four lateral parallel connections, described work The quantity of electrode is four, and the installation position of these four working electrodes lays respectively in described four laterals, these four work Electrode is working electrode 5, working electrode 6, working electrode 12, working electrode 13 respectively, and, these four working electrodes its Specific antigen in the gold size sensitive membrane structure of top layer is four kinds of cholera antigenic substances that can be specific binding to cholera antibody respectively, These four kinds of antigenic substances be respectively cholera TP0821 antigen and cholera TP0319 antigen and cholera TP0624 antigen and Cholera O139 antigen, from the point of view of specifically launching, 5 is in its top layer gold size sensitive membrane structure being installed in lateral 4 Specific antigenic substance is the working electrode of cholera TP0821 antigen, and 6 is that its top layer gold size being installed in lateral 7 is quick The working electrode that specific antigenic substance is cholera TP0319 antigen in sense membrane structure, 12 is to be installed in lateral 11 Its top layer gold size sensitive membrane structure in the working electrode that specific antigenic substance is cholera TP0624 antigen, 13 be installing The work that specific antigenic substance is cholera O139 antigen electricity in its top layer gold size sensitive membrane structure in lateral 14 Pole, described working electrode 5, working electrode 6, working electrode 12, its material of working electrode 13 are gold material or thermal decomposition Conducting polymer material, described working electrode 5, working electrode 6, working electrode 12, its pattern of working electrode 13 present sheet Shape or thread, it is important that, this its material of substrate 22 is polydimethylsiloxane material, and this its surface of substrate 22 is primary shape The surface of state, the surface of this primary form its be intended to refer to not through any surface chemical modification or any surface chemical modification The surface of primary form of this material, the structure of this device also includes hinge-type fixture 15, this its profile of hinge-type fixture 15 Profile likeness in form hinge, this hinge-type fixture 15 is by two hinges 20,25 being mutually hinged and runs through this two pages One of sheet 20,25 fastening screw 17 and one are mated with this fastening screw 17 and are socketed in one with this fastening screw 17 The nut 26 for manually fastening and hand break loose risen is constituted, and two hinges 20,25 of this hinge-type fixture 15 are each with it This micro-fluidic chip is mutually drawn close and clamped to tip, and described tip is positioned at the knot of the neighbouring described terminal 24 of this micro-fluidic chip On structure position, a described hinge at least in attaches fixing being equiped with in miniature ultrasonic transducer units, this legend, is In hinge 20 attach install this miniature ultrasonic transducer units 19, it is of course also possible to allow in two hinges 20,25 all Miniature ultrasonic transducer units in installing, but, it is, in general, that only attach one miniature ultrasonic of installing in a described hinge Transducer just be enough to deal be actually needed, and, higher-order of oscillation electric signal transmission cable 18, this higher-order of oscillation electric signal transmits One end of cable 18 links together with this miniature ultrasonic transducer units 19；This hinge-type fixture 15 provides a convenience should The function that device is disassembled；This its major function of miniature ultrasonic transducer units 19 is when the actual sample introduction of micro-fluidic chip is tested, profit The interfacial tension between the inwall of sample solution and described pipeline is reduced so that it is can be compatible with its ultrasound wave launched, and And, utilize the range difference between described sample introduction end 23 and described terminal 24 and this miniature ultrasonic transducer units 19 installation position Difference on different and its ultrasonic intensity experienced, its interfacial tension of sample introduction end 23 and described terminal described in induced synthesis Difference between 24 its interfacial tensions, these two ends of this micro-fluidic chip i.e. interfacial tension between sample introduction end 23 and terminal 24 is poor Different meeting i.e. forms pressure gap at these two ends of this micro-fluidic chip between sample introduction end 23 and terminal 24, this pressure gap can drive Dynamic sample solution flows to described terminal 24 direction；This its function of miniature ultrasonic transducer units 19 also includes being launched with it Ultrasound wave checks its absorption on described inner surface of pipeline of biomacromolecule contained in sample, and then checks this poly dimethyl Its body of substrate 22 of siloxanes material is relative to the effect of swallowing up of this biomacromolecule；The substrate of described polydimethylsiloxane material 22 its functions include and cover plate 21 and working electrode 5, working electrode 6, working electrode 12, working electrode 13 and to electrode 8 And reference electrode 9 together builds this micro-fluidic chip, soft and have elasticity this polydimethylsiloxane material substrate 22 its Function also includes, with the character of its absorption strong to ultrasound wave, strongly absorbing ultrasound wave, and thereby at this micro-fluidic chip This terminal 24 is to the rapid decrement realizing ultrasonic intensity within the limited short distance between this sample introduction end 23.

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

Fig. 1 is depicted without in this hinge-type fixture 15 and one hinge being attached this miniature ultrasonic transducer units of installing 19 and higher-order of oscillation electric signal transmission cable 18；Further, Fig. 1 and Fig. 2 is all depicted without described higher-order of oscillation electric signal The associate members such as generator and multiple tracks electrochemical workstation.

Involved hinge-type fixture 15 can utilize commercially available hinge simply to cut, change a social system；Described miniature ultrasonic transducing Device 19 is commercially available；Commercially available miniature ultrasonic transducer units is various in style, can select as required to use；This miniature ultrasonic Wave transducer 19 can also customize to ultrasonic transducer specialized factory.

Involved higher-order of oscillation electric signal transmission cable 18 is commercially available；Can also be to ultrasonic transducer producer or cable special manufacturer Family's customization.

There is the product close to needs commercially available on involved higher-order of oscillation electric signal generator market；Can also customize to relevant manufacturers.

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.

This case device is to detect multiple corresponding cholera antibody, thereby cholera diagnosis with multiple cholera antigen.

Claims (10)

1. its substrate of chip uses the cholera diagnosis micro fluidic device of strong hydrophobic material, and the structure of this micro fluidic device includes manifold Road micro-fluidic chip, the structure of this micro-fluidic chip includes bonded to each other being installed in substrate together and cover plate, described substrate and lid Sheet is plate object or tablet, and that face towards this cover plate of this substrate is contained and formed via mould pressing process or etching technics Channel structure, this substrate possibly together be connected with this channel structure and pierce this substrate via mould pressing process, etching technics or letter The window structure that single drilling technology is formed, this substrate being installed together bonded to each other and this cover plate have been built into jointly containing pipeline Structure and the micro-fluidic chip of liquid pool structure being attached thereto, the locations of structures of this pipeline is positioned at this substrate and mutually pastes with this cover plate The interface zone closed, its side of this window is blocked by this cover plate and opposite side is open, and the locations of structures of this window is exactly described liquid pool Locations of structures, the quantity of described liquid pool is three, and two its locations of structures of liquid pool therein are positioned at the sample introduction of this micro-fluidic chip End, the end of its chip liquid flowing when remaining its locations of structures of liquid pool is positioned at the test of this micro-fluidic chip actual sample introduction End, this terminal is located remotely from each other with this sample introduction end, and one end of this pipeline is via the manifold being similarly positioned in this interface zone bonded to each other Shape turnout respectively be positioned at this Liang Ge liquid pool UNICOM of sample introduction end, the other end of this pipeline and the described end being positioned at this micro-fluidic chip This remaining liquid pool UNICOM of end, and, the working electrode that is sequentially respectively installed in this pipeline on diverse location and right Electrode and reference electrode, described working electrode by conductive electrode and be attached on this conductive electrode to have embedded cholera special The gold size sensitive membrane of heterogenetic antibody is constituted, and the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is by four branches Pipeline 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 described four In lateral, and, the specific antigen in its top layer gold size sensitive membrane structure of these four working electrodes is to resist cholera respectively Four kinds of cholera antigenic substances that physical ability is specific binding, these four kinds of antigenic substances are cholera TP0821 antigen and cholera respectively TP0319 antigen and cholera TP0624 antigen and cholera O139 antigen, its material of described working electrode is gold material Or thermal decomposition conducting polymer material, its pattern of described working electrode presents lamellar or thread, it is characterised in that its material of this substrate Matter is polydimethylsiloxane material, and its surface of this substrate is the surface of primary form, the surface of this primary form its be meant to It is not through the surface of primary form of this material of any surface chemical modification or any surface chemical modification, the knot of this device Structure also includes hinge-type fixture, and this its appearance profile of hinge-type fixture likeness in form hinge, this hinge-type fixture is by being mutually hinged Two hinges and run through one of these two hinges fastening screw and one mate with this fastening screw and with this fastening spiral shell The nut for manually fastening and hand break loose that silk braid is connected together is constituted, and two hinges of this hinge-type fixture are respectively with its tip Mutually drawing close and clamp this micro-fluidic chip, described tip is positioned at the locations of structures of the neighbouring described terminal of this micro-fluidic chip On, in a described hinge at least in, attaching is fixing is equiped with miniature ultrasonic transducer units, and, higher-order of oscillation telecommunication Number transmission cable, one end of this higher-order of oscillation electric signal transmission cable links together with this miniature ultrasonic transducer units；This hinge Formula fixture provides a function facilitating this device to disassemble；Its major function of this miniature ultrasonic transducer units is at micro-fluidic chip During the test of actual sample introduction, its ultrasound wave launched is utilized to open to reduce the interface between the inwall of sample solution and described pipeline 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 checking its table in described pipeline of biomacromolecule contained in sample with its ultrasound wave launched Absorption on face, and then check its body of the substrate effect of swallowing up relative to this biomacromolecule of this polydimethylsiloxane material；Institute State its function of substrate of polydimethylsiloxane material to include and cover plate and working electrode and electrode and reference electrode are together built This micro-fluidic chip, soft and this polydimethylsiloxane material of having elasticity its function of substrate also includes with it strong to ultrasound wave The character of strong absorption, absorbs strongly to ultrasound wave, and thereby having between this terminal of this micro-fluidic chip to this sample introduction end The rapid decrement of ultrasonic intensity is realized within the short distance of limit.

Its substrate of chip the most according to claim 1 uses the cholera diagnosis micro fluidic device of strong hydrophobic material, its feature Being, described pipeline and described lateral and described manifold shape turnout are capillary channel.

Its substrate of chip the most according to claim 1 uses the cholera diagnosis micro fluidic device of strong hydrophobic material, its feature Being, described thermal decomposition conducting polymer is the conductive material formed after anoxybiotic heat treatment by polyimides or polyacrylonitrile.

Its substrate of chip the most according to claim 1 uses the cholera diagnosis micro fluidic device of strong hydrophobic material, its feature Be, the width of described working electrode or diameter between 0.1 micron to 2000 micron, and, described working electrode Length is between 1 micron to 15000 micron.

Its substrate of chip the most according to claim 1 uses the cholera diagnosis micro fluidic device of strong hydrophobic material, its feature Being, the thickness of described gold size sensitive membrane is between 10 nanometers and 200 nanometers.

Its substrate of chip the most according to claim 1 uses the cholera diagnosis micro fluidic device of strong hydrophobic material, its feature Being, its material of described cover plate in structure is polydimethylsiloxane material.

Its substrate of chip the most according to claim 1 uses the cholera diagnosis micro fluidic device of strong hydrophobic material, its feature Be, be positioned at this micro-fluidic chip this sample introduction end these two liquid pools its with to be positioned at this of this this terminal of micro-fluidic chip remaining Air line distance between one liquid pool is between 3 centimetres and 7 centimetres.

Its substrate of chip the most according to claim 1 uses the cholera diagnosis micro fluidic device of strong hydrophobic material, its feature Being, described cover plate in structure and its thickness of substrate are all between 1.0 millimeters and 5.0 millimeters.

Its substrate of chip the most according to claim 1 uses the cholera diagnosis micro fluidic device of strong hydrophobic material, its feature Being, the structure of this micro fluidic device also includes higher-order of oscillation electric signal generator, described higher-order of oscillation electric signal transmission cable its The other end is connected with this higher-order of oscillation electric signal generator.

Its substrate of chip the most according to claim 1 uses the cholera diagnosis micro fluidic device of strong hydrophobic material, its feature Being, its specified ultrasonic emitting power of this miniature ultrasonic transducer units is between 5 milliwatts and 9000 milliwatts, and this is miniature super The frequency of its ultrasound wave operationally launched of acoustic wave transducer is between 100KHz and 12MHz.