CN107649196A

CN107649196A - Liquid stream driving is with the easily-disassembled controller used in syphilis diagnosis micro fluidic device of adapter

Info

Publication number: CN107649196A
Application number: CN201610626868.1A
Authority: CN
Inventors: 洪小女
Original assignee: Individual
Current assignee: Individual
Priority date: 2016-07-26
Filing date: 2016-07-26
Publication date: 2018-02-02

Abstract

The present invention relates to a kind of easily-disassembled controller used in syphilis diagnosis micro fluidic device of liquid stream driving adapter, belong to analysis testing field.With dimethyl silicone polymer i.e. PDMS that is cheap and easily processing to make controller used in syphilis diagnosis with the substrate of micro-fluidic chip be a technical goal；But its surface of the material is strongly hydrophobic, and targetedly surface is modified or surface modification, its effect are difficult to persistently, and this case aims to solve the problem that the serial relevant issues.This case main points are, the selected PDMS with ecosystem surface of substrate, and by the elastic clip that miniature ultrasonic transducer units are attached on its clamping limb with elastic force snap-in location in its neighbor positions of the sample liquid stream terminal of the micro-fluidic chip, interfacial tension is reduced with ultrasonic wave, strong absorbability using PDMS to ultrasonic wave simultaneously, reach ultrasonic intensity rapid decrement in short distance, so as to form interfacial tension difference at the both ends of the chip, sample liquid stream is thereby facilitated to be flowed along originally hydrophobic capillary channel to the terminal direction.

Description

Liquid stream driving is with the easily-disassembled controller used in syphilis diagnosis micro fluidic device of adapter

Technical field

The present invention relates to a kind of easily-disassembled controller used in syphilis diagnosis micro fluidic device of liquid stream driving adapter, the micro-fluidic dress Put is to belong to analysis testing field based on antigen/antibody specific reaction come the special purpose device of Diagnosis of Syphilis antigen.

Background technology

The micro-fluidic controller used in syphilis diagnosis technical background of associated multi-channel, may refer to the patents of invention such as CN 200910152141.4 Application case.

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

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

The basic framework of micro-fluidic chip, including be etched with the substrate of small fluid course and fit together therewith Cover plate, the small fluid course on the substrate, before upper cover plate is assembled, it is apparent on see to be exactly some micro-channels, to wait until After covering cover plate thereon, just really closure forms the small fluid course, the conduit inner surface of the micro-channel together with The part cover plate that surround the micro-channel forms described small fluid course together；So, it is clear that after assembling completes The small fluid course, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, should The state or property of micro-channel inner surface substantially determine the integrality or property of the small fluid course；Therefore say, this The inner surface state or inner surface property of micro-channel of the individual structure on substrate are key factors；In principle, it is any can The material of its solid forms is kept or kept substantially, can be used to make substrate and cover plate, such as, it can act as substrate and lid The material of piece can be monocrystalline silicon piece, quartz plate, sheet glass, high polymer for example dimethyl silicone polymer, polymethyl methacrylate, Makrolon etc.；Certainly, the selection of substrate and the selection of cover plate be able to can also be differed with identical；From material consumption, make From the point of view of difficulty and application popularization prospect etc. etc., not small difference, the especially choosing of that substrate between these materials be present Material, have a great influence.

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

But thing is really not so simple.

First, this polydimethyl siloxane material, that is, the material that alphabetical PDMS is referred to of abridging, itself are a kind of strong Strong hydrophobic material, micro-channel is built on this material, if without being operated for the modified of the micro-channel surface, that , after overall assembling is completed, that is, after covering cover plate, because the micro-channel its inner surface in structure occupies most liquid The inner surface of circulation road, then, its strong hydrophobic property of the PDMS micro-channels inner surface, is deciding factor, it can cause Similar to the aqueous solution the fine liquid stream of polar liquid by becoming very difficult, its flow resistance is big, or even in general is micro- Pump is all difficult to promote, certainly, if cover plate also selects to use the PDMS material, then, problem is substantially identical, similar； Therefore, among prior art, modification is modified particular for the micro-channel inner surface on the PDMS material, is necessary behaviour Make；So, this is pretty troublesome for the modified operation of PDMS micro-channel inner surfacesThat falls nor this problem, is formed tight Weight technology puzzlement, be another problem：PDMS polymer molecules inside its body phase of this PDMS material substrate have automatic The characteristic diffuse to the surface, migrated, the spy that this substrate body phase inside PDMS polymer molecules are diffused to the surface, migrated automatically Property, the state after modification by its inner surface of that micro-channel of surface modifying and decorating will be caused can not to maintain long enough Time, the holding time for micro-channel its inner surface state after that is surface-modified be substantially only sufficient to complete laboratory internal The time of test experiments needs；In other words, by surface modification or the PDMS micro-channel inner surfaces of surface modification, it is modified The surface state that is formed can not be lasting afterwards or after saying modification, but soon automatically tends to or say and become surface modification again Surface state before, the strong hydrophobic surface state of that script is returned in the shorter time, then, just think, this The micro-fluidic chip of sample can largely make, mass storage, be widely popularized, and answer is it is obvious that is, impossible.This Micro-channel on PDMS material, if not doing surface modification, similar to the aqueous solution the fine liquid stream of polar solvent can not pump it is logical Cross, chip also cannot just use；And if having done surface modification, its state after modifying can not be persistently kept again, or together Sample can not popularization and application.

So, how to accomplish that substrate can either be made using cheap PDMS material, and the microflute can be released Road inner surface decorating state can not persistently, chip can not largely make, largely lay in and then be widely popularized and such a make ability The puzzlement that the numerous professionals in domain are entangled with for a long time, the highly difficult problem that exactly one its obvious technology barrier can not despise.

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

Second, the PDMS material of non-surface modification, it is stated that, its surface is strongly hydrophobic above, this strong hydrophobic Material surface and also have another problem, that is, this strong hydrophobic PDMS surfaces can adsorb large biological molecule, and And these adsorbed large biological molecules can also further depression further on PDMS surfaces, gradually fall into it is gradually deep, until It is heavy to be trapped within the body phase of PDMS substrates, in fact, this process, partly it is also due to PDMS material body phase interior polymer Molecule, which has, to be diffused to the surface, caused by travel motion；Such case, it can also be explained from another angle, i.e. continue not Disconnectedly from inside PDMS body phases to those polymer molecules of its diffusion into the surface, migration, its result moved, be little by little by that It has been involved in a bit by the large biological molecule of adsorption within the body phase of PDMS substrates, briefly, these adsorbed biologies Macromolecular is exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up the phenomenon of large biological molecule, its institute Caused by influence, necessarily cause the severe deviations of all kinds of test data of experiment for being related to large biological molecule.

As described above, the problem of PDMS substrates, is, its not only adsorption large biological molecule, and swallow up biological big point Son, so, as the large biological molecule of experiment test object, its disappearance will not stop because surface saturation is adsorbed, and It is, it is constantly adsorbed, also constantly swallowed up.

On PDMS substrates, its body phase is constantly swallowed up and tests showing for associated biomolecule macromolecular in related experiment test process As, it is to say that another kind, which is explained, substantial amounts of Minute pores in PDMS body phases be present, associated biomolecule macromolecular by after adsorption, Depression enters these Minute pores, and then is swallowed up；However, inventor thinks, those can allow the sky of miniature scale Qi leel squeezes into the Minute pores therebetween, not equal to saying that they also can directly allow the large biological molecule of relative large scale to enter Enter, both difference on yardstick are huge, must not make sweeping generalizations.Explanation is bypassed, in any case, as dependence test analysis object Large biological molecule is adsorbed by PDMS substrate micro-channels inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is person in charge of reception at ceremonies Phenomenon existing for sight.

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

So, how can either obtain that PDMS material price is extremely cheap, substrate makes extremely easy benefit, and can is enough Reach and contain the absorption process of the PDMS substrate micro-channel inner surfaces to large biological molecule for a long time, and then prevent PDMS substrate body phases The effect of swallowing up to large biological molecule so that related chip manufactured goods be able to maintain that one it is prolonged enough, reasonably guarantee the quality Phase, it is exactly a very intractable problem.The problem equally makes this area numerous as another problem addressed above Professional is entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise. Also be present many year in the problem, so far, also not yet properly settled.

The content of the invention

The technical problem to be solved by the invention is to provide a package solution, solves totally above Two problems addressed, also, the solution is applied to controller used in syphilis diagnosis multichannel micro-fluidic chip field, formed a kind of New controller used in syphilis diagnosis multichannel micro-fluidic device.

The present invention solves the technical problem by following scheme, and the device that the program provides is that a kind of liquid stream is driven with attached Add the controller used in syphilis diagnosis micro fluidic device that part is easily-disassembled, the structure of the micro fluidic device includes multichannel micro-fluidic chip, and this is micro- The structure of fluidic chip includes being bonded to each other the substrate and cover plate of installing together, and the substrate and cover plate are plate object or piece The channel structure via mould pressing process or etching technics formation, the base are contained in shape thing, that face towards the cover plate of the substrate Piece also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or simple drilling technology shape Into window structure, be bonded to each other the substrate that is installed together and the cover plate be built into jointly containing pipeline configuration and with Connected liquid pool structure micro-fluidic chip, the locations of structures of the pipeline be located at the interface that the substrate and the cover plate are bonded to each other Region, its side of the window is blocked by the cover plate and opposite side opens, and the locations of structures of the window is exactly the structure of the liquid pool Position, the quantity of the liquid pool is three, and its locations of structures of two liquid pools therein is located at the sample introduction end of the micro-fluidic chip, remaining Under the liquid flowing in its chip when being located at the actual sample introduction test of the micro-fluidic chip of liquid pool its locations of structures terminal, should Terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is branched off via the manifold shape for being similarly positioned in the interface zone being bonded to each other Road respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline with positioned at the micro-fluidic chip the terminal A remaining liquid pool UNICOM, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and right Electrode and reference electrode, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded syphilis The gold size sensitive membrane of specific antibody is formed, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by four Lateral is in parallel to be formed, and the quantity of the working electrode is four, and the installation position of four working electrodes is located at institute respectively State in four laterals, and, the specific antibody in its top layer gold size sensitivity membrane structure of four working electrodes is respectively The four kinds of syphilis antibody materials that can be specifically bound to Treponema pallidum antigen, four kinds of antibody materials are syphilis specific antibody respectively TP0684, TP0453, TP0821 and TP0319, its material of the working electrode are gold material or thermal decomposition conducting polymer material Sheet or thread is presented in matter, its pattern of the working electrode, and emphasis is that its material of the substrate is dimethyl silicone polymer material, Its surface of the substrate is the surface of primary form, the surface of the primary form its be intended to refer to and do not pass through any surface chemistry The surface of the primary form of the material of modification or any surface chemical modification, the structure of the micro fluidic device also include elastic force Folder, two opposite clamping limb snap-in locations of the elastic clip are in the position of the neighbouring terminal of the micro-fluidic chip, at least Fixation is attached described in one of which on clamping limb and is equiped with miniature ultrasonic transducer units, and, higher-order of oscillation electric signal passes Transmission cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable link together；The elastic clip Provide a function of facilitating the micro fluidic device to disassemble；Its major function of the miniature ultrasonic transducer units is in micro-fluidic core During the test of piece actual sample introduction, the ultrasonic wave launched using it reduces the interface between sample solution and the inwall of the pipeline Tension force, can be compatible, also, utilizes the sample introduction end and the terminal and the miniature ultrasonic transducer units installation position The distance between difference on difference and its ultrasonic intensity experienced, its interfacial tension of sample introduction end described in induced synthesis With the difference between the terminal its interfacial tension, the interfacial tension difference between the micro-fluidic chip both ends can be in the miniflow Pressure gap is formed between the both ends of control chip, the pressure gap can drive sample solution to the end flow；This is miniature The ultrasonic wave that ultrasonic transducer its function also includes being launched with it check large biological molecule contained in sample its in institute The absorption on inner surface of pipeline is stated, and then checks the substrate of the dimethyl silicone polymer material its body phase to the large biological molecule The effect of swallowing up；Its function of the substrate of the dimethyl silicone polymer material is included with cover plate and working electrode and to electrode and reference Electrode together builds the micro-fluidic chip, soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and also include With its property to the strong absorption of ultrasonic wave, ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic chip, the terminal arrives The rapid decrement of ultrasonic intensity is realized within limited short distance between the sample introduction end, it is micro-fluidic that its locations of structures is located at this A remaining liquid pool for the terminal of liquid flowing is also referred to as terminal liquid pool in its chip when the actual sample introduction of chip is tested, the end Some high hydroscopic resin particles are filled with the liquid pool of end, its opening end of the terminal liquid pool is covered by breathable microporous film.

Described miniature ultrasonic transducer units can certainly be all installed on two clamping limbs；But only install one Miniature ultrasonic transducer units are dealt with and used enough.

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

The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and syphilis specific antibody-solutions uniformly, is used a little Sample instrument point sample is coated on specified structure position, and forms its drying and forming-film.Syphilis specific in the gold size sensitive membrane Antibody is the syphilis antibody of horseradish peroxidase or glucose oxidase mark, and the gold size sensitive membrane has been included as solid Determine above-mentioned each syphilis specific antibody and introduce complementary medium therein, the complementary medium such as chitosan, acetic acid are fine Dimension is plain, gelatin is therein a kind of or their mixture.

The pipeline and the lateral and the manifold shape turnout in the microfluidic chip structure, in it Footpath size may each be arbitrarily selected size, still, for as far as possible less with prepare liquid sample and reduction reagent loss etc. Consideration, the pipeline and the lateral and the manifold shape turnout preferably select capillary level passage, institute The passage for stating capillary level implies that its internal diameter passage suitable with the internal diameter of the capillary on ordinary meaning.The capillary is in it The shape of cross section of portion's passage can be arbitrary shape, and the shape of cross section is for example circular, oval, square, rectangle, bar Shape, naturally it is also possible to it is the linear of bending arbitrarily be present, also, the interior shape of the capillary is with the extension of pipeline, The shape of cross section of different parts can also allow to be different shapes.Only for the word of capillary one, its art-recognized meanings is public Know.

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

It is related to several liquid pools in this case microfluidic chip structure, the liquid pool is the pond shape or capsule for transitional liquid storage Shape constructs, and its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, and the cavity shape is for example round Cylindrical cavity shape, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..The size of the liquid pool can be any Selected size, still, in order to as far as possible less with prepare liquid sample and reduce reagent loss, the liquid pool be preferably capable of with The liquid pool of the microminiature of capillary matching.

Only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field, It is known.

Various sizes, variously-shaped ultrasonic transducer are commercially available；Its size of commercially available miniature ultrasonic transducer units It may diminish to the magnitude only calculated with millimeter.

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

Only with regard to naked PDMS substrates itself micro-channel molding or lithographic technique for, be open-and-shut known skill Art；Similarly, the technology of hole-opening is even more known simple technique on naked PDMS substrates.This case is not also superfluous to this expansion Speech.

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

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

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

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

Only for the word of high hydroscopic resin one art-recognized meanings of itself, come for the professional of chemical field Say, be known.

The high hydroscopic resin is commercially available.

Only for the word of breathable microporous film one art-recognized meanings of itself, for the professional of technical field of membrane, It is known.

The breathable microporous film is commercially available.

This case device can further include some annexes certainly, and the annex is such as multiple tracks electrochemical workstation Deng the art-recognized meanings of the multiple tracks electrochemical workstation are known.The each work being related in this case microfluidic chip structure Electrode and to electrode and reference electrode etc., special it can get lines crossed and the multiple tracks electrochemical workstation via corresponding respectively The corresponding interface coupled.It is described that special to get lines crossed be for by each phase of each electrode and the multiple tracks electrochemical workstation Answer the private cable that interface is coupled to each other.The micro-fluidic chip in this case device, its structure can also include micro-valve, The quantity of the micro-valve is unlimited, and according to being actually needed, the micro-valve can be installed in any need in the microfluidic chip structure Position to be mounted；The word of micro-valve one is for the professional of micro fluidic chip technical field, the art-recognized meanings of itself It is known；The micro-valve itself manufacturing technology and the use of technology is also known；The component that the micro-valve is not required.

The diameter of the working electrode can allow to be that any setting is easily installed the suitable diameter used, still, It is recommending or say preferable its scope of the diameter between 0.1 micron to 2000 microns；The length of the working electrode can To allow to be that any setting is easily installed the length used, it is however recommended to or to say the preferable length its scope be 1 Micron is between 15000 microns.

It is installed in by spraying or point sample instrument point sample or the coating of other appropriate process described in the working electrode surface layer Gold size sensitive membrane, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness, It is however recommended to thickness preferable thickness is between 10 nanometers and 200 nanometers in other words.

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

Positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal should Air line distance between a remaining liquid pool can be arbitrarily selected suitable distance, still, the distance as needed Preferred value is between 3 centimetres and 7 centimetres.

Described its thickness of cover plate and substrate can allow be any setting the thickness for being easy to assembling, the thickness of recommendation or say Preferable thickness is between 1.0 millimeters and 5.0 millimeters.Less thickness is advantageous to save material.

The application method of this case micro-fluidic chip：

Itd is proposed first based on this case and the first public new liquid stream driving principle, its application of this case micro-fluidic chip are transported Among work, the new liquid stream driving method is determined completely without involving any additional Micropump.

The interfacial tension difference that this case is formed between micro-fluidic chip both ends caused by the ultrasonic wave, Driving liquid stream flows in the capillary channel of the four-way micro-fluidic chip, right respectively using four-way electrochemical analytical instrument Four kinds of controller used in syphilis diagnosis antigens are detected.

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

1st, blood serum sample liquid is added in micro-pipe road, under ultrasonic wave driving, various Treponema pallidum antigen molecules are by each logical In road on electrode surface gold size sensitive membrane embed corresponding horseradish peroxidase-labeled syphilis specific antibody capture.

2nd, the syphilis specific antibody of horseradish peroxidase-labeled is formed immune multiple with the Treponema pallidum antigen in blood serum sample Compound.

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

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

It is an advantage of the invention that in elastic force described in the terminal of the micro-fluidic chip its close position snap-in location Folder, with the clamping limb of the elastic clip institute attaching install miniature ultrasonic transducer units, the low-power launched using it, high frequency The ultrasonic wave of frequency range so that without inside strong hydrophobic micro-fluidic chip of surface chemical modification or surface chemical modification Compatibility between its tube wall of pipeline and the test object aqueous solution is significantly increased, and this is existing by providing one for sample liquid stream Real possibility；Meanwhile using its strong absorbability to ultrasonic wave of dimethyl silicone polymer substrate, in shorter distance It is interior, it is, in from the terminal to the very short distance of only several centimeters yardsticks the sample introduction end, it is strong to reach ultrasonic wave The rapid decrement of degree, the difference of the interfacial tension is thereby caused at the both ends of the micro-fluidic chip, and then, using this two Pressure gap between its both ends for being formed of the difference of interfacial tension between end, driving sample liquid stream is in such a original Flowed in this strong hydrophobic capillary channel to the terminal direction.By this case liquid stream drive scheme, entirely without must be to this The substrate and its internal pipeline of dimethyl silicone polymer material carry out any surface chemical modification or chemical modification, altogether dispense with The laborious procedures of the surface chemical modification or chemical modification；And setting for traditional Micropump etc is altogether dispensed with It is standby；On the other hand, the ultrasonic wave of the low-power, high-frequency band, additionally it is possible to contain the large biological molecule in sample at this without modification Naked its inner surface of pipeline of dimethyl silicone polymer substrate on absorption, and then contain its body of the dimethyl silicone polymer substrate The effect of swallowing up of relatively described large biological molecule；The Reversible binding thing of the antigen, antibody and antigen and antibody is all certainly Belong to the type of described large biological molecule；Because described suction-operated and the described effect of swallowing up effectively are contained, Therefore, dependence test result will be better able to objectively reflect actual conditions；The effect of the low-power, high-frequency band ultrasonic wave, Certainly also include facilitating the Reversible binding between antigen, antibody react it is quick reach, this causes dependence test operates can be with Completed than faster speed.

Due to surface chemical modification or chemistry for its relevant surfaces of the dimethyl silicone polymer substrate need not be carried out Modified operation, therefore, this surface chemical modification layer or chemically modified layer not need to exist, then, the poly dimethyl Its body phase interior polymer molecule of siloxanes substrate constantly diffuses to the surface automatically, migrate caused by it to the surface chemistry The damaging influence of decorative layer or chemically modified layer is also just not present.

It is related that the technical scheme of this case has dissolved its application to dimethyl silicone polymer substrate addressed above totally A series of technical barriers.Based on this case scheme, the very cheap polydimethyl siloxane material of this kind is just possible in miniflow Control chip prepare, production, using etc. field play bigger effect.

The miniature ultrasonic transducer units have been installed in fixation on the elastic clip its clamping limb in this case structure, and the structure carries A function of facilitating the device to disassemble is supplied, in this way, the elastic clip just can together with miniature ultrasonic transducer units appended thereon It is enough to be easily mutually disengaged with the micro-fluidic chip, then, the component that the part can freely depart from just can circulate benignly it is heavy It is multiple to use many times；The architectural feature is advantageous to save the use cost of the device.

Brief description of the drawings

Fig. 1 is the schematic diagram of this case micro fluidic device embodiment chip part construction, it is shown that this structure Depression angle under chip internal pipeline and the structural form of each electrode and each related liquid pool, do not depict in the figure described Elastic clip and the miniature ultrasonic transducer units set up thereon and other annexes.

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

In figure, 1,2,10 be the different liquid pool of three installation positions respectively, and 3 be manifold shape turnout, and 4,7,11,14 are respectively Installation position is different but four laterals parallel with one another for forming UNICOM's structure in parallel, and 5 be its that be installed in lateral 4 The working electrode that specific antibody material in the gold size sensitivity membrane structure of top layer is syphilis specific antibody TP0684,6 be installing The specific antibody material in its top layer gold size sensitivity membrane structure in lateral 7 is syphilis specific antibody TP0453's Working electrode, 12 be that specific antibody material in its top layer gold size sensitivity membrane structure being installed in lateral 11 is syphilis Specific antibody TP0821 working electrode, 13 be the spy in its top layer gold size sensitivity membrane structure being installed in lateral 14 Heterogenetic antibody material is syphilis specific antibody TP0319 working electrode, and 8 be to electrode, and 9 be reference electrode, and 15 be elastic force Folder, 16,21 be two clamping limbs of elastic clip respectively, and 17 be the terminal of the micro-fluidic chip, and 18 be the micro-fluidic chip The sample introduction end, 19 be the substrate of dimethyl silicone polymer material, and 20 be cover plate, and 22 be miniature ultrasonic transducer units, and 23 are Higher-order of oscillation electric signal transmission cable, 24 be tension spring；The spring clamp structure in legend is only the legend structure of signal, real Border spring clamp structure is not limited to the legend spring clamp structure；Arrow in legend indicate the micro-fluidic chip its in actual fortune During row, driven by pressure at two ends difference, the flow direction of its sample liquid stream.

Embodiment

In this case that Fig. 1 and Fig. 2 are shown embodiment, the structure of the micro fluidic device includes multichannel micro-fluidic core Piece, the structure of the micro-fluidic chip include being bonded to each other the substrate 19 and cover plate 20 of installing together, the substrate 19 and cover plate 20 be plate object or tablet, and that face towards the cover plate 20 of the substrate 19 is contained via mould pressing process or etching technics The channel structure of formation, the substrate 19 also containing be connected with the channel structure and pierce the substrate via mould pressing process, quarter The window structure that etching technique or simple drilling technology are formed, is bonded to each other the substrate 19 being installed together and the cover plate 20 is common Be built into the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the liquid pool be liquid pool 1, liquid pool 2, Liquid pool 10, the locations of structures of the pipeline are located at the interface zone that the substrate 19 is bonded to each other with the cover plate 20, its side of the window Blocked and opposite side opening by the cover plate 20, the locations of structures of the window is exactly the liquid pool 1, liquid pool 2, the structure bit of liquid pool 10 Put, the quantity of the liquid pool is three, and two liquid pools therein are that liquid pool 1 and liquid pool 2 its locations of structures are located at the micro-fluidic core The sample introduction end 18 of piece, a remaining liquid pool be when liquid pool 10 its locations of structures is located at the micro-fluidic chip actual sample introduction test its The terminal 17 that liquid flows in chip, the terminal 17 is located remotely from each other with the sample introduction end 18, and one end of the pipeline is via being similarly positioned in The manifold shape turnout 3 of the interface zone being bonded to each other, should respectively with the liquid pool 1 positioned at sample introduction end 18 and the UNICOM of liquid pool 2 The other end of pipeline and a remaining liquid pool for the terminal 17 positioned at the micro-fluidic chip are the UNICOM of liquid pool 10, with And sequentially it is respectively installed in working electrode in the pipeline on diverse location and to electrode 8 and reference electrode 9, the work Make electrode by conductive electrode and the gold size sensitive membrane for having embedded syphilis specific antibody being attached on the conductive electrode Form, the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of four lateral parallel connections, the work The quantity for making electrode is four, and the installation position of four working electrodes is located in four laterals respectively, this four Working electrode is working electrode 5, working electrode 6, working electrode 12, working electrode 13 respectively, and, four working electrodes its Specific antibody in the gold size sensitivity membrane structure of top layer is the four kinds of syphilis antibody things that can be specifically bound to Treponema pallidum antigen respectively Matter, four kinds of antibody materials are syphilis specific antibody TP0684, TP0453, TP0821 and TP0319 respectively, are specifically deployed For, 5 be that specific antibody material in its top layer gold size sensitivity membrane structure being installed in lateral 4 is syphilis specific Antibody TP0684 working electrode, 6 be the specific antibody in its top layer gold size sensitivity membrane structure being installed in lateral 7 Material is syphilis specific antibody TP0453 working electrode, and 12 be its top layer gold size sensitive membrane being installed in lateral 11 The working electrode that specific antibody material in structure is syphilis specific antibody TP0821,13 are installed in lateral 14 Its top layer gold size sensitivity membrane structure in specific antibody material be syphilis specific antibody TP0319 working electrode, it is described Working electrode 5, working electrode 6, working electrode 12, working electrode 13 its material are gold material or thermal decomposition conducting polymer material Sheet or thread is presented in matter, the working electrode 5, working electrode 6, working electrode 12, working electrode 13 its pattern, and emphasis is, Its material of the substrate 19 is dimethyl silicone polymer material, and its surface of substrate 19 is the surface of primary form, the primary form Surface its be intended to refer to the primary shape of the not material by any surface chemical modification or any surface chemical modification The surface of state, the structure of the device also include elastic clip 15, two opposite clamping limbs 16,21 snap-in locations of the elastic clip 15 Fixed installing is attached in the position of the neighbouring terminal 17 of the micro-fluidic chip, on a clamping limb at least in There are a miniature ultrasonic transducer units 22, in legend, the miniature ultrasonic transducer units 22 are to attach to be installed on one of folder In gripping arm 21, and, higher-order of oscillation electric signal transmission cable 23, one end of the higher-order of oscillation electric signal transmission cable 23 is micro- with this Type ultrasonic transducer 22 links together；The elastic clip 15 provides a function of facilitating the device to disassemble；This is miniature super Its major function of acoustic wave transducer 22 is in the test of micro-fluidic chip actual sample introduction, and the ultrasonic wave launched using it is reduced Interfacial tension between the inwall of sample solution and the pipeline, can be compatible, also, using the sample introduction end 18 and The distance between the terminal 17 and the installation position of miniature ultrasonic transducer units 22 difference and its ultrasonic wave experienced Difference between difference in intensity, its interfacial tension of sample introduction end 18 described in induced synthesis and the terminal 17 its interfacial tension, The micro-fluidic chip both ends be interfacial tension difference between sample introduction end 18 and terminal 17 can the micro-fluidic chip this two End is to form pressure gap between sample introduction end 18 and terminal 17, and the pressure gap can drive sample solution to the direction of terminal 17 Flowing；Its function of miniature ultrasonic transducer units 22 also ultrasonic wave including being launched with it checks biology contained in sample Its absorption on the inner surface of pipeline of macromolecular, and then check the substrate 19 of the dimethyl silicone polymer material its body phase pair The effect of swallowing up of the large biological molecule；Its function of the substrate 19 of the dimethyl silicone polymer material includes and cover plate 20 and work Electrode 5, working electrode 6, working electrode 12, working electrode 13 and the micro-fluidic core is together built to electrode 8 and reference electrode 9 Piece, it is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and also include with it to the strong absorption of ultrasonic wave Property, ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic chip terminal to limited short between the sample introduction end The rapid decrement of ultrasonic intensity is realized within distance, its locations of structures is located at its core when the actual sample introduction of the micro-fluidic chip is tested A remaining liquid pool for the terminal that liquid flows is also referred to as terminal liquid pool in piece, is inhaled in the terminal liquid pool filled with some height Water-resin particle, its opening end of the terminal liquid pool are covered by breathable microporous film.

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

Miniature ultrasonic transducer units 22 and high frequency vibrating that the elastic clip 15 is depicted without in Fig. 1 and is set up thereon Swing electric signal transmission cable 23；Also, the higher-order of oscillation electric signal generator and multiple tracks electricity are depicted without in Fig. 1 and Fig. 2 The associate members such as chem workstation.

Involved elastic clip 15 is commercially available.It is available for the commercially available alternative spring clamp structure and make that this case structure uses Type and size etc., quality is various, and specific elastic clip pattern can be selected as needed.

Involved miniature ultrasonic transducer units 22 are commercially available；It can also be customized to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal transmission cable 23 is commercially available；Can also be special to ultrasonic transducer producer or cable Industry producer customizes.

Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；It can also determine to relevant manufacturers System.

Each working electrode in this example structure and can be respectively via each special electricity to electrode and reference electrode Cable or say is being got lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as annex or saying interface connection of getting lines crossed.

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

Claims

1. the easily-disassembled controller used in syphilis diagnosis micro fluidic device of liquid stream driving adapter, the structure of the micro fluidic device includes leading to more Road micro-fluidic chip, the structure of the micro-fluidic chip include being bonded to each other the substrate and cover plate of installing together, the substrate and Cover plate is plate object or tablet, and that face towards the cover plate of the substrate is contained via mould pressing process or etching technics shape Into channel structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etch work The window structure that skill or simple drilling technology are formed, it is bonded to each other the substrate being installed together and is built into jointly with the cover plate Micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the locations of structures of the pipeline are located at the substrate with being somebody's turn to do The interface zone that cover plate is bonded to each other, its side of the window is blocked by the cover plate and opposite side opens, the locations of structures of the window It is exactly the locations of structures of the liquid pool, the quantity of the liquid pool is three, and it is micro- that its locations of structures of two liquid pools therein is located at this The sample introduction end of fluidic chip, its locations of structures of a remaining liquid pool are located at its chip when the actual sample introduction of the micro-fluidic chip is tested The terminal of interior liquid flowing, the terminal are located remotely from each other with the sample introduction end, and one end of the pipeline is bonded to each other via this is similarly positioned in Interface zone manifold shape turnout respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline with positioned at should A remaining liquid pool UNICOM for the terminal of micro-fluidic chip, and, sequentially it is respectively installed in different positions in the pipeline The working electrode put and to electrode and reference electrode, the working electrode is by conductive electrode and is attached to the conduction Property electrode on embedded syphilis specific antibody gold size sensitive membrane form, the construction of the pipeline is in parallel construction, described to be in The pipeline of parallel construction is made up of four lateral parallel connections, and the quantity of the working electrode is four, four working electrodes Installation position respectively in four laterals, and, its top layer gold size sensitivity membrane structure of four working electrodes In specific antibody be the four kinds of syphilis antibody materials that can be specifically bound to Treponema pallidum antigen respectively, four kinds of antibody materials point Be not syphilis specific antibody TP0684, TP0453, TP0821 and TP0319, its material of the working electrode be gold material or Conducting polymer material is thermally decomposed, sheet or thread is presented in its pattern of the working electrode, it is characterised in that its material of the substrate Dimethyl silicone polymer material, its surface of the substrate is the surface of primary form, the surface of the primary form its be meant to It is that this is micro-fluidic not by any surface chemical modification or the surface of the primary form of the material of any surface chemical modification The structure of device also includes elastic clip, and two opposite clamping limb snap-in locations of the elastic clip are in the neighbouring of the micro-fluidic chip The position of the terminal, fixation is attached on a clamping limb at least in and is equiped with miniature ultrasonic transducer units, with And higher-order of oscillation electric signal transmission cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable Link together；The elastic clip provides a function of facilitating the micro fluidic device to disassemble；The miniature ultrasonic transducer units its Major function be in the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it reduce sample solution with it is described Interfacial tension between the inwall of pipeline, can be compatible, also, miniature with this using the sample introduction end and the terminal Difference in the distance between ultrasonic transducer installation position difference and its ultrasonic intensity experienced, induced synthesis Difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension, the boundary between the micro-fluidic chip both ends Face tension difference can form pressure gap between the both ends of the micro-fluidic chip, the pressure gap can drive sample solution to The end flow；The ultrasonic wave that its function of the miniature ultrasonic transducer units also includes being launched with it is checked contained in sample Large biological molecule its absorption on the inner surface of pipeline, and then check the substrate of the dimethyl silicone polymer material its body With respect to the effect of swallowing up of the large biological molecule；Its function of the substrate of the dimethyl silicone polymer material includes and cover plate and work Electrode and the micro-fluidic chip is together built to electrode and reference electrode, soft dimethyl silicone polymer material for simultaneously having elasticity Substrate its function also include with its property to the strong absorption of ultrasonic wave, ultrasonic wave is absorbed strongly, and thereby at this To the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end, it is tied the micro-fluidic chip terminal Structure position is located at a remaining liquid for the terminal of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested Pond is also referred to as terminal liquid pool, is filled with some high hydroscopic resin particles in the terminal liquid pool, and its opening end of the terminal liquid pool is breathed freely Microporous barrier is covered.

2. the easily-disassembled controller used in syphilis diagnosis micro fluidic device of liquid stream driving adapter according to claim 1, its feature It is, the pipeline and the lateral and the manifold shape turnout are capillary channel.

3. the easily-disassembled controller used in syphilis diagnosis micro fluidic device of liquid stream driving adapter according to claim 1, its feature It is, the thermal decomposition conducting polymer is the electric conductivity material formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated Material.

4. the easily-disassembled controller used in syphilis diagnosis micro fluidic device of liquid stream driving adapter according to claim 1, its feature Be, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the length of the working electrode Degree is between 1 micron to 15000 microns.

5. the easily-disassembled controller used in syphilis diagnosis micro fluidic device of liquid stream driving adapter according to claim 1, its feature It is, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.

6. the easily-disassembled controller used in syphilis diagnosis micro fluidic device of liquid stream driving adapter according to claim 1, its feature It is, the cover plate its material in structure is dimethyl silicone polymer material.

7. the easily-disassembled controller used in syphilis diagnosis micro fluidic device of liquid stream driving adapter according to claim 1, its feature Be, positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with the remainder positioned at the micro-fluidic chip terminal A liquid pool between air line distance between 3 centimetres and 7 centimetres.

8. the easily-disassembled controller used in syphilis diagnosis micro fluidic device of liquid stream driving adapter according to claim 1, its feature It is, described its thickness of cover plate and substrate in structure is between 1.0 millimeters and 5.0 millimeters.

9. the easily-disassembled controller used in syphilis diagnosis micro fluidic device of liquid stream driving adapter according to claim 1, its feature It is, the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission cable Its other end is connected with the higher-order of oscillation electric signal generator.

10. the easily-disassembled controller used in syphilis diagnosis micro fluidic device of liquid stream driving adapter according to claim 1, its feature It is, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 5 milliwatts and 5000 milliwatts, the miniature ultrasonic The frequency of its ultrasonic wave operationally launched of wave transducer is between 100KHz and 12MHz.