CN106153957A - Strong hydrophobic PDMS is as the hypotype swine flue detection chip apparatus of substrate material - Google Patents

Abstract

The present invention relates to a kind of strong hydrophobic PDMS hypotype swine flue detection chip apparatus as substrate material, belong to analysis field tests.The polydimethylsiloxane inexpensively and easily processed i.e. PDMS is used to there is many obstacles to the substrate making hypotype swine flue diagnosis micro-fluidic chip；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

Strong hydrophobic PDMS is as the hypotype swine flue detection chip apparatus of substrate material

Technical field

The present invention relates to a kind of strong hydrophobic PDMS hypotype swine flue detection chip apparatus as substrate material, belong to analysis and survey Examination field.

Background technology

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

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

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

The basic framework of micro-fluidic chip, including the substrate being etched with small fluid course and the cover plate fit together therewith, Small fluid course on described substrate, before fit on cover plate, apparent on see to be exactly some micro-channel, wait until thereon After covering cover plate, just real Guan Bi forms described small fluid course, and the conduit inner surface of this micro-channel is together with surround this The part cover plate of micro-channel constitutes described small fluid course together；So, it is clear that this after assembling completes is small Fluid course, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, in this micro-channel The state on surface or character substantially determine integrality or the character of this small fluid course；Therefore saying, this builds at base Inner surface state or the inner surface character of the micro-channel on sheet are key factors；In principle, any can keep or substantially protect Hold the material of its solid forms, can be used to make substrate and cover plate, such as, it is possible to the material as substrate and cover plate is permissible It is monocrystalline silicon piece, piezoid, sheet glass, high polymer such as polydimethylsiloxane, polymethyl methacrylate, Merlon etc. Deng；Certainly, the selection of substrate can be identical with the selection of cover plate, it is also possible to differs；From material consumption, manufacture difficulty and From the point of view of application popularization prospect etc. aspect, there is the selection of the least difference, especially that substrate between these materials, impact is relatively Greatly.

In various substrates make material, polydimethylsiloxane, i.e. PDMS, the easiest molding, so Substrate on to make micro-channel extremely simple, and this lower cost for material, make substrate with this polydimethyl siloxane material, Suppress or etch micro-channel thereon, and the cover plate made with glass or the cheap material such as polypropylene or other plastic sheet matches, It is a kind of more satisfactory selection seemingly；Certainly, patch material can also select to use cheap polydimethyl siloxane material: So, this substrate selection is the scheme of polydimethyl siloxane material, and material is extremely cheap, makes extremely simple, seems and should also be as It is extremely easy to popularize, promote.

But, thing is really not so simply.

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

So, how to accomplish to utilize cheap PDMS material to make substrate, and table in described micro-channel can be released Face decorating state cannot persistently, chip cannot make in a large number, lay in a large number and then be widely popularized and such a make this area numerous specially The puzzlement that industry personnel are entangled with for a long time, it is simply that the highly difficult problem that its obvious technology barrier can not be despised.

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

Its two, the PDMS material of non-surface modification, above it is stated that, its surface is the most hydrophobic, this most hydrophobic Material surface and also another problem, that is, biomacromolecule can be adsorbed in the most hydrophobic this PDMS surface, and And, the depression that these adsorbed biomacromolecules also can be further on PDMS surface further, gradually falls into gradually deep, directly To the heavy body phase being trapped in PDMS substrate, in fact, this process, partly it is also due to PDMS material body internal mutually Polymer molecule have diffuse to the surface, travel motion is caused；This situation, it is also possible to explain from another angle, i.e. Internal to its diffusion into the surface, those polymer molecules of migration, the result of its motion mutually by PDMS body continuously, be by Within those gradually have been involved in the body phase of PDMS substrate by the biomacromolecule of surface adsorption, briefly, these are inhaled Attached biomacromolecule is swallowed up mutually by PDMS substrate body exactly；So, this PDMS substrate body swallows up biomacromolecule mutually Phenomenon, its impact caused, necessarily cause the severe deviations relating to all kinds of test data of experiment of biomacromolecule.

As it has been described above, the problem of PDMS substrate is, its not only surface adsorption biomacromolecule, and swallow up biomacromolecule, So, its disappearance of biomacromolecule as experiment test object will not stop because of the saturated absorption in surface, but, no Disconnected adsorbed, the most constantly swallowed up.

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

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

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

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 hypotype swine flue diagnosis multichannel micro-fluidic chip field, forms one Novel hypotype swine flue diagnosis Multichannel device.

The present invention solves described technical problem by following scheme, and the device that the program provides is that a kind of strong hydrophobic PDMS is as base The hypotype swine flue detection chip apparatus of sheet material, the structure of this device includes multichannel micro-fluidic chip, this micro-fluidic chip Structure include bonded to each other being installed in substrate together and cover plate, described substrate and cover plate are plate object or tablet, this base The channel structure formed via mould pressing process or etching technics is contained in that face towards this cover plate of sheet, this substrate possibly together with this Channel structure is connected and pierces the window structure formed via mould pressing process, etching technics or simple drilling technology of this substrate, This substrate being installed together bonded to each other and this cover plate have been built into jointly containing pipeline configuration and the liquid pool knot 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 one 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, the number of described liquid pool Amount is three, and two its locations of structures of liquid pool therein are positioned at the sample introduction end of this micro-fluidic chip, remaining its structure of liquid pool The terminal of its chip liquid flowing when position is positioned at the test of this micro-fluidic chip actual sample introduction, this terminal is the most remote with this sample introduction end 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 should Liang Ge liquid pool UNICOM, this remaining liquid pool UNICOM of the other end of this pipeline and the described terminal being positioned at this micro-fluidic chip, And, the working electrode that is sequentially respectively installed in this pipeline on diverse location and to electrode and reference electrode, described work Electrode is sensitive by conductive electrode and the gold size having embedded hypotype swine flue specific antigen that is attached on this conductive electrode Film is constituted, and the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is made up of three lateral parallel connections, described The quantity of working electrode is three, and the installation position of these three working electrodes lays respectively in described three laterals, and, Specific antigen in its top layer gold size sensitive membrane structure of these three working electrodes is to hypotype swine flue antibody energy specificity respectively In conjunction with three kinds of hypotype swine flue antigenic substances, these three kinds of antigenic substances are hypotype swine flue specific antigen H respectively₁N₁、H₃N₂ And H₁N₂, its material of described working electrode be gold material or thermal decomposition conducting polymer material, its pattern of described working electrode in Existing lamellar or thread, it is important that, its material of this substrate is polydimethylsiloxane material, and its surface of this substrate is primary form Surface, the surface of this primary form its be intended to refer to not through any surface chemical modification or any surface chemical modification should The surface of the primary form of material, the structure of this device also includes hinge-type fixture, and this its appearance profile of hinge-type fixture likeness in form is closed Page, this hinge-type fixture is by two hinges being mutually hinged and the fastening screw and running through these two hinges The individual nut for manually fastening and hand break loose mated with this fastening screw and be connected together with this fastening turnbuckle is constituted, should This micro-fluidic chip is respectively mutually drawn close and clamp to two hinges of hinge-type fixture with its tip, and it is micro-fluidic that described tip is positioned at this In the locations of structures of the neighbouring described terminal of chip, in a described hinge at least in, attaching is fixing is equiped with miniature ultrasonic Wave transducer, and, higher-order of oscillation electric signal transmission cable, one end of this higher-order of oscillation electric signal transmission cable is miniature super with this Acoustic wave transducer links together；This hinge-type fixture provides a function facilitating this device to disassemble；This miniature ultrasonic changes Can its major function of device be when micro-fluidic chip actual sample introduction test, utilize its ultrasound wave launched to reduce sample solution and Interfacial tension between the inwall of described pipeline so that it is can be compatible, and, utilize described sample introduction end and described terminal and be somebody's turn to do Distance difference between miniature ultrasonic transducer units installation position and the difference on its ultrasonic intensity experienced, induce shape Become the difference between described its interfacial tension of sample introduction end and its interfacial tension of described terminal, the boundary between these two ends of this micro-fluidic chip Surface tension difference can form pressure gap between these two ends of this micro-fluidic chip, and this pressure gap can drive sample solution to institute State end flow；Its function of this miniature ultrasonic transducer units also includes checking life contained in sample with its ultrasound wave launched Its absorption on described inner surface of pipeline of thing macromole, and then check its body of substrate of this polydimethylsiloxane material and relatively should The effect of swallowing up of biomacromolecule；Its function of substrate of described polydimethylsiloxane material includes and cover plate and working electrode and right Electrode and reference electrode together build this micro-fluidic chip, soft and have its merit of substrate of this polydimethylsiloxane material of elasticity Can also include, with the character of its absorption strong to ultrasound wave, ultrasound wave being absorbed strongly, and thereby should at this micro-fluidic chip Terminal is to the rapid decrement realizing ultrasonic intensity within the limited short distance between this sample introduction end.

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

Described pipeline in described microfluidic chip structure 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 device can also include higher-order of oscillation electric signal generator；It is another for described higher-order of oscillation electric signal transmission cable One end can be connected with this higher-order of oscillation electric signal generator.

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

The preferred scope of its specified ultrasonic emitting power of this miniature ultrasonic transducer units be between 5 milliwatts and 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 triple channel micro-fluidic chip, utilizes multi-channel electrochemical analyzer device respectively to three kinds of hypotypes Swine flue diagnostic antigen is detected.

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

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

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

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

3, use multi-channel electrochemical analyzer, add the electron mediators such as catechol, use the above-mentioned reaction of amperometric detection The curent change caused, is derived from kind and the content of various analyte.

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

It is an advantage of the invention that its close position of described terminal at described micro-fluidic chip 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 device of this case.

In figure, 1,2,8 is the liquid pool that three installation positions are different respectively, and 3 is manifold shape turnout, and 4,9,12 are respectively Installation position is different but three laterals forming UNICOM in parallel structure parallel with one another, and 5 is its that be installed in lateral 4 Specific antigenic substance in the gold size sensitive membrane structure of top layer is hypotype swine flue specific antigen H₁N₁Working electrode, 10 are Specific antigenic substance in its top layer gold size sensitive membrane structure being installed in lateral 9 is that hypotype swine flue specificity resists Former H₃N₂Working electrode, 11 is the specific antigen thing in its top layer gold size sensitive membrane structure being installed in lateral 12 Matter is hypotype swine flue specific antigen H₁N₂Working electrode, 6 is to electrode, and 7 is reference electrode, and 13 is hinge-type fixture, 14 indicate linkwork position, and 15 is fastening screw, and 16 is higher-order of oscillation electric signal transmission cable, and 17 is miniature super Acoustic wave transducer, 18,23 is two hinges that locations of structures is different respectively, and 19 is cover plate, and 20 is substrate, and 21 is sample introduction End, 22 is terminal, and 24 is nut；This hinge-type clamp structure in legend is only the legend structure of signal, this hinge actual Its structure of formula fixture is not limited to this legend hinge-type clamp structure；Arrow in legend indicate this micro-fluidic chip its in reality During operation, 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 20 together and cover plate 19, and described substrate 20 and cover plate 19 are Plate object or tablet, that face towards this cover plate 19 of this substrate 20 is contained and is formed via mould pressing process or etching technics Channel structure, this substrate 20 possibly together be connected with this channel structure and pierce this substrate 20 via mould pressing process, etching work The window structure that skill or simple drilling technology are formed, this substrate 20 being installed together bonded to each other builds jointly with this cover plate 19 Having become containing pipeline configuration and the micro-fluidic chip of liquid pool structure that is attached thereto, the locations of structures of this pipeline is positioned at this substrate 20 interface zones bonded to each other with this cover plate 19, its side of this window is blocked by this cover plate 19 and opposite side is open, this window Mouthful locations of structures be exactly the locations of structures of described liquid pool, the quantity of described liquid pool is three, these three liquid pools be respectively liquid pool 1, Liquid pool 2, liquid pool 8, the i.e. liquid pool 1 of two liquid pools therein and its locations of structures of liquid pool 2 are positioned at the sample introduction end of this micro-fluidic chip 21, its chip liquid stream when a remaining liquid pool i.e. its locations of structures of liquid pool 8 is positioned at the test of this micro-fluidic chip actual sample introduction Dynamic terminal 22, this terminal 22 is located remotely from each other with this sample introduction end 21, and one end of this pipeline is bonded to each other via being similarly positioned in this Interface zone manifold shape turnout 3 respectively be positioned at this two liquid pools i.e. liquid pool 1 and liquid pool 2 UNICOM of sample introduction end 21, should This remaining liquid pool i.e. liquid pool 8 UNICOM of the other end of pipeline and the described terminal 22 being positioned at this micro-fluidic chip, and, The working electrode that is sequentially respectively installed in this pipeline on diverse location and to electrode 6 and reference electrode 7, described work electricity Pole is by conductive electrode and the gold size sensitive membrane having embedded hypotype swine flue 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 three lateral parallel connections, described work The quantity making electrode is three, and the installation position of these three working electrodes lays respectively in described three laterals, and, should Specific antigen in three its top layer gold size sensitive membrane structures of working electrode is to tie hypotype swine flue antibody energy specificity respectively The three kinds of hypotype swine flue antigenic substances closed, these three kinds of antigenic substances are hypotype swine flue specific antigen H respectively₁N₁、H₃N₂And H₁N₂, from the point of view of concrete expansion, 5 is the specific antigen thing in its top layer gold size sensitive membrane structure being installed in lateral 4 Matter is hypotype swine flue specific antigen H₁N₁Working electrode, 10 is that its top layer gold size being installed in lateral 9 is sensitive Specific antigenic substance in membrane structure is hypotype swine flue specific antigen H₃N₂Working electrode, 11 is to be installed in branched pipe The specific antigenic substance in its top layer gold size sensitive membrane structure in road 12 is hypotype swine flue specific antigen H₁N₂Work Electrode, its material of described working electrode is gold material or thermal decomposition conducting polymer material, and its pattern of described working electrode presents Lamellar or thread, it is important that, this its material of substrate 20 is polydimethylsiloxane material, and this its surface of substrate 20 is primary The surface of form, the surface of this primary form its be intended to refer to not change through any surface chemical modification or any surface chemistry The surface of the primary form of this material of property, the structure of this device also includes hinge-type fixture 13, and this hinge-type fixture 13 is outside it Shape profile likeness in form hinge, this hinge-type fixture 13 is by two hinges 18,23 being mutually hinged and runs through these two One of hinge 18,23 fastening screw 15 and one are mated with this fastening screw 15 and are socketed in this fastening screw 15 The nut 24 for manually fastening and hand break loose together is constituted, and this nut 24 in legend is a kind of butterfly nut, should Planting butterfly nut relatively convenient in practical operation, two hinges 18,23 of this hinge-type fixture 13 are respectively mutually leaned on its tip Holding together and clamp this micro-fluidic chip, described tip is positioned in the locations of structures of neighbouring described terminal 22 of this micro-fluidic chip, Attach in a described hinge i.e. hinge 18 at least in or hinge 23 and fixing be equiped with miniature ultrasonic transducer units 17, In this example, this miniature ultrasonic transducer units 17 is to attach to be installed in hinge 18, and, higher-order of oscillation electric signal transmission electricity Cable 16, one end of this higher-order of oscillation electric signal transmission cable 16 links together with this miniature ultrasonic transducer units 17；This conjunction Page fixture 13 provides a function facilitating this device to disassemble；This its major function of miniature ultrasonic transducer units 17 be During the test of micro-fluidic chip actual sample introduction, utilize its ultrasound wave launched to reduce between the inwall of sample solution and described pipeline Interfacial tension so that it is can be compatible, and, utilize described sample introduction end 21 and described terminal 22 and this miniature ultrasonic Distance difference between transducer 17 installation position and the difference on its ultrasonic intensity experienced, described in induced synthesis Difference between its interfacial tension of sample introduction end 21 and its interfacial tension of described terminal 22, between these two ends of this micro-fluidic chip Interfacial tension difference can form pressure gap between these two ends of this micro-fluidic chip, this pressure gap can drive sample solution to Described terminal 22 flows；This its function of miniature ultrasonic transducer units 17 also includes checking in sample with its ultrasound wave launched Contained its absorption on described inner surface of pipeline of biomacromolecule, and then check the substrate of this polydimethylsiloxane material 20 its bodies are relative to the effect of swallowing up of this biomacromolecule；Its function of substrate 20 of described polydimethylsiloxane material includes and lid Sheet 19 and working electrode 5,10,11 and electrode 6 and reference electrode 7 together build this micro-fluidic chip, soft also have bullet Its function of substrate 20 of this polydimethylsiloxane material of property also includes with the character of its absorption strong to ultrasound wave, to ultrasonic Ripple absorbs strongly, and thereby limited short distance between this terminal of this micro-fluidic chip 22 to this sample introduction end 21 it Inside realize the rapid decrement of ultrasonic intensity.

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 13 and one hinge this miniature ultrasonic transducer units 17 set up And higher-order of oscillation electric signal transmission cable 16；Further, Fig. 1 and Fig. 2 is all depicted without described higher-order of oscillation electric signal to send out The raw associate member such as device and multiple tracks electrochemical workstation.

Involved miniature ultrasonic transducer units 17 is commercially available；Can also customize to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal transmission cable 16 is commercially available；Can also customize to ultrasonic transducer producer.

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

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.

Involved hinge-type fixture 13 itself can utilize commercially available hinge simply to cut the transformation of the way.Hinge-type folder in legend The configuration of tool 13 is only an example, and the configuration of this case hinge-type fixture is not limited to the configuration in this legend.

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

Claims (10)

1. The strongest hydrophobic PDMS is as the hypotype swine flue detection chip apparatus of substrate material, and the structure of this device includes that multichannel is micro- Fluidic chip, the structure of this micro-fluidic chip includes bonded to each other being installed in substrate together and cover plate, and described substrate and cover plate are equal For plate object or tablet, the conduit formed via mould pressing process or etching technics is contained in that face towards this cover plate of this substrate Structure, this substrate is possibly together with being connected with this channel structure and piercing via mould pressing process, etching technics or simply beating of this substrate The window structure that hole technique is formed, this substrate being installed together bonded to each other and this cover plate have been built into jointly containing pipeline configuration And the micro-fluidic chip of the liquid pool structure being attached thereto, it is bonded to each other with this cover plate that the locations of structures of this pipeline is positioned at this substrate Interface zone, its side of this window is blocked by this cover plate and opposite side is open, and the locations of structures of this window is exactly the knot of described liquid pool Structure position, the quantity of described liquid pool is three, and two its locations of structures of liquid pool therein are positioned at the sample introduction end of this micro-fluidic chip, The terminal 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, should Terminal is located remotely from each other with this sample introduction end, and one end of this pipeline is via the manifold shape turnout being similarly positioned in this interface zone bonded to each other Respectively be positioned at this Liang Ge liquid pool UNICOM of sample introduction end, the other end of this pipeline be positioned at this micro-fluidic chip described terminal should A remaining liquid pool UNICOM, and, the working electrode that is sequentially respectively installed in this pipeline on diverse location and to electrode with And reference electrode, described working electrode by conductive electrode and be attached on this conductive electrode to have embedded hypotype swine flue special The gold size sensitive membrane of Specific Antigen is constituted, and the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is by three branches Pipeline parallel connection is constituted, and the quantity of described working electrode is three, and the installation position of these three working electrodes lays respectively at described three In lateral, and, the specific antigen in its top layer gold size sensitive membrane structure of these three working electrodes is to hypotype pig respectively Three kinds of hypotype swine flue antigenic substances that influenza antibodies energy is specific binding, these three kinds of antigenic substances are that hypotype swine flue is special respectively Property antigen H₁N₁、H₃N₂And H₁N₂, its material of described working electrode is gold material or thermal decomposition conducting polymer material, described work Make its pattern of electrode and present lamellar or thread, it is characterised in that its material of this substrate is polydimethylsiloxane material, this substrate Its surface is the surface of primary form, the surface of this primary form its be intended to refer to not through any surface chemical modification or appoint The surface of the primary form of this material of what surface chemical modification, the structure of this device also includes hinge-type fixture, and this hinge-type presss from both sides Having its appearance profile likeness in form hinge, this hinge-type fixture is by two hinges being mutually hinged and runs through these two hinges One fastening screw and one mates with this fastening screw and are fastened and hands for manual with what this fastening turnbuckle was connected together The dynamic nut got loose is constituted, and this micro-fluidic chip, institute are respectively mutually drawn close and clamp to two hinges of this hinge-type fixture with its tip State tip to be positioned in the locations of structures of neighbouring described terminal of this micro-fluidic chip, a described hinge at least in is pasted Attached fixing is equiped with miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, this higher-order of oscillation electric signal transmits One end of cable links together with this miniature ultrasonic transducer units；This hinge-type fixture provides one and facilitates this device to disassemble Function；Its major function of this miniature ultrasonic transducer units is when the actual sample introduction of micro-fluidic chip is tested, and utilize that it is launched is super Sound wave reduces the interfacial tension between the inwall of sample solution and described pipeline so that it is can be compatible, and, enter described in utilization Distance difference between sample end and described terminal and this miniature ultrasonic transducer units installation position and its experienced ultrasonic Difference in intensity of wave, difference between its interfacial tension of sample introduction end and its interfacial tension of described terminal described in induced synthesis, this is micro- Interfacial tension difference between these two ends of fluidic chip can form pressure gap, this pressure between these two ends of this micro-fluidic chip Difference can drive sample solution to described end flow；Its function of this miniature ultrasonic transducer units also include with its launched ultrasonic Ripple checks its absorption on described inner surface of pipeline of biomacromolecule contained in sample, and then checks this polydimethylsiloxanes Its body of the substrate of alkane material is relative to the effect of swallowing up of this biomacromolecule；Its functional packet of substrate of described polydimethylsiloxane material Include and cover plate and working electrode and electrode and reference electrode are together built this micro-fluidic chip, soft this poly-diformazan also having elasticity Its function of the substrate of radical siloxane material also includes, with the character of its absorption strong to ultrasound wave, strongly absorbing ultrasound wave, And thereby realize the quick of ultrasonic intensity within limited short distance between this terminal of this micro-fluidic chip to this sample introduction end Successively decrease.
2. Strong hydrophobic PDMS the most according to claim 1 is as the hypotype swine flue detection chip apparatus of substrate material, and it is special Levying and be, described pipeline and described lateral and described manifold shape turnout are capillary channel.
3. Strong hydrophobic PDMS the most according to claim 1 is as the hypotype swine flue detection chip apparatus of substrate material, and it is special Levying and be, described thermal decomposition conducting polymer is the electric conductivity material formed after anoxybiotic heat treatment by polyimides or polyacrylonitrile Material.
4. Strong hydrophobic PDMS the most according to claim 1 is as the hypotype swine flue detection chip apparatus of substrate material, and it is special Levy and be, the width of described working electrode or diameter between 0.1 micron to 2000 micron, and, described working electrode Length between 1 micron to 15000 micron.
5. Strong hydrophobic PDMS the most according to claim 1 is as the hypotype swine flue detection chip apparatus of substrate material, and it is special Levying and be, the thickness of described gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. Strong hydrophobic PDMS the most according to claim 1 is as the hypotype swine flue detection chip apparatus of substrate material, and it is special Levying and be, its material of described cover plate in structure is polydimethylsiloxane material.
7. Strong hydrophobic PDMS the most according to claim 1 is as the hypotype swine flue detection chip apparatus of substrate material, and it is special Levy and be, be positioned at this micro-fluidic chip this sample introduction end these two liquid pools its with this remainder being positioned at this this terminal of micro-fluidic chip A liquid pool between air line distance between 3 centimetres and 7 centimetres.
8. Strong hydrophobic PDMS the most according to claim 1 is as the hypotype swine flue detection chip apparatus of substrate material, and it is special Levying and be, described cover plate in structure and its thickness of substrate are all between 1.0 millimeters and 5.0 millimeters.
9. Strong hydrophobic PDMS the most according to claim 1 is as the hypotype swine flue detection chip apparatus of substrate material, and it is special Levying and be, the structure of this device also includes higher-order of oscillation electric signal generator, described higher-order of oscillation electric signal transmission cable its another End is connected with this higher-order of oscillation electric signal generator.
10. Strong hydrophobic PDMS the most according to claim 1 as the hypotype swine flue detection chip apparatus of substrate material, its Being characterised by, its specified ultrasonic emitting power of this miniature ultrasonic transducer units is between 5 milliwatts and 9000 milliwatts, and this is micro- The frequency of its ultrasound wave operationally launched of type ultrasonic transducer is between 100KHz and 12MHz.