CN107649201A - The controller used in syphilis diagnosis device that sample driving can be removed fast with function element - Google Patents

Abstract

The present invention relates to the controller used in syphilis diagnosis device that a kind of sample driving can be removed fast with function element, belong to analysis testing field.Some problems be present with dimethyl silicone polymer i.e. PDMS that is cheap and easily processing to make the substrate of controller used in syphilis diagnosis micro-fluidic chip；Its surface of the PDMS 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 the chain ring type magnetic holding device for being equiped with miniature ultrasonic transducer units socket is positioned at the sample liquid stream terminal of the micro-fluidic chip its neighbor positions, 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

The controller used in syphilis diagnosis device that sample driving can be removed fast with function element

Technical field

The present invention relates to the controller used in syphilis diagnosis device that a kind of sample driving can be removed fast with function element, belongs to analysis and surveys Examination field.

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 200910160439.X 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 for miniflow Past of control technology, now, and, vision of the future etc. etc., suffer from detail, be deep into long opinion of detail State.

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 device.

The present invention solves the technical problem by following scheme, and the device that the program provides is that a kind of sample driving is diligent The controller used in syphilis diagnosis device that energy element can be removed fast, the structure of the device include multichannel micro-fluidic chip, the micro-fluidic core The structure of piece includes being bonded to each other installing substrate and cover plate together, and the substrate and cover plate are plate object or tablet, The channel structure via mould pressing process or etching technics formation is contained in that face towards the cover plate of the substrate, and the substrate also contains There is the window formed via mould pressing process, etching technics or simple drilling technology for being connected and piercing the substrate with the channel structure Mouth structure, it is bonded to each other the substrate being installed together and has been built into containing pipeline configuration and has been attached thereto jointly with the cover plate Liquid pool structure micro-fluidic chip, the locations of structures of the pipeline is located at the interface zone that the substrate is bonded to each other with the cover plate, 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 locations of structures of the liquid pool, 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 When one liquid pool its locations of structures is located at the micro-fluidic chip actual sample introduction test in its chip liquid flowing terminal, the terminal It is located remotely from each other with the sample introduction end, one end of the pipeline is via the manifold shape turnout point for being similarly positioned in the interface zone being bonded to each other Should not with the terminal positioned at the micro-fluidic chip with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline A remaining liquid pool UNICOM, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode And reference electrode, the working electrode by conductive electrode and be attached on the conductive electrode to have embedded syphilis special Property antigen gold size sensitive membrane form, the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by four branches Pipeline 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 described four respectively In bar lateral, and, the specific antigen in its top layer gold size sensitivity membrane structure of four working electrodes is to plum respectively Four kinds of Treponema pallidum antigen materials that malicious antibody can be specifically bound, four kinds of antigenic substances are syphilis specific antigen 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 device also include chain ring type electromagnetic clamp Tool, six links is shared in its structure of the chain ring type magnetic holding device, the link is in strip, shaft-like or bar-shaped, each adjacent ring Section is hinged to form chain link, the hexagonal cyclic structure of its appearance profile of the chain link, each top of the hexagonal annular structure Its locations of structures of angle is articulated structure position, and two therein of the hexagonal annular structure is in its material of the link of opposite side position Matter is magnetic conductivity material, and its material of the remaining four processes of the hexagonal annular structure is non-magnetic material, described non magnetic Material refers to the material not responded strongly to externally-applied magnetic field, in a link among two links of the magnetic conductivity material Magnet exciting coil is wound with, the link for being wound with magnet exciting coil is respectively equiped with one in the both sides neighbor positions of its magnet exciting coil The pole shoe of magnetic conductivity material, two pole shoes are shared, two pole shoes are directed to the link of another magnetic conductivity material, and this is another Attach to fix on its surface of the link of one magnetic conductivity material and be equiped with miniature ultrasonic transducer units, rely on electromagnetism adhesive strength The chain ring type magnetic holding device is socketed the close position for being positioned at its terminal of the micro-fluidic chip, and, higher-order of oscillation telecommunication Number transmission cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable link together；The chain Ring type magnetic holding device provides a function of facilitating the device to disassemble；Its major function of the miniature ultrasonic transducer units is micro- During the test of fluidic chip actual sample introduction, the ultrasonic wave launched using it is reduced between sample solution and the inwall of the pipeline Interfacial tension, can be compatible, also, filled using the sample introduction end and the terminal and the miniature ultrasonic transducer units If the difference on the distance between position difference and its ultrasonic intensity experienced, its boundary of sample introduction end described in induced synthesis Difference between face tension force and the terminal its interfacial tension, interfacial tension difference between the micro-fluidic chip both ends can be Pressure gap is formed 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 checks large biological molecule contained in sample Its absorption on the inner surface of pipeline, and then it is big to the biology to check its body phase of the substrate of the dimethyl silicone polymer material The effect of swallowing up of molecule；Its function of the substrate of the dimethyl silicone polymer material is included with cover plate and working electrode and to electrode It is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and reference electrode together builds the micro-fluidic chip Also include with its property to the strong absorption of ultrasonic wave, ultrasonic wave is absorbed strongly, and thereby should in the micro-fluidic chip Terminal is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end, and its locations of structures was positioned at should A remaining liquid pool for the terminal of liquid flowing is also referred to as terminal liquid in its chip when the actual sample introduction of micro-fluidic chip is tested Pond, some high hydroscopic resin particles are filled with the terminal liquid pool, its opening end of the terminal liquid pool is covered by breathable microporous film.

The word of magnet exciting coil one art-recognized meanings of itself are known.

The word of magnetic conductivity material one art-recognized meanings of itself are known；The material for belonging to magnetic conductivity material is for example pure Iron, silicon steel, soft magnetic ferrite etc..

Non magnetic material described in this case refers to the material not responded strongly to externally-applied magnetic field, belongs to the non magnetic material The material of matter such as metallic copper, metallic zinc, ormolu, metallic aluminium, almag etc..

The be hinged word art-recognized meanings of itself field in Machine Design is known.

The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and syphilis specific antigenic solution 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 Antigen is the Treponema pallidum antigen of horseradish peroxidase or glucose oxidase mark, and the gold size sensitive membrane has been included as solid Determine above-mentioned each syphilis specific antigen 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 device can also include higher-order of oscillation electric signal generator；The higher-order of oscillation electric signal transmission cable Its other end can be connected with the higher-order of oscillation electric signal generator.

The involved higher-order of oscillation electric signal generator technology of itself, 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 9000 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 syphilis antibodies are detected.

Corresponding four kinds of syphilis antibodies are detected with four kinds of Treponema pallidum antigens, with detecting corresponding four with four kinds of syphilis antibodies Kind Treponema pallidum antigen, similarly, can Diagnosis of Syphilis；The principle of its foundation is, necessarily antigen, antibody in syphilis sufferer body And deposit, and mutual Reversible binding forms reversible conjugate, therefore, antibody and thereby Diagnosis of Syphilis is detected with antigen, with Antibody goes to detect antigen and Diagnosis of Syphilis, can reach diagnostic purpose.Certainly, its corresponding electrode sensitive of different means is repaiied Adorn layer technically and differ.

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 syphilis antibody molecules are by each logical In road on electrode surface gold size sensitive membrane embed corresponding horseradish peroxidase-labeled syphilis specific antigen capture.

2nd, the syphilis specific antigen of horseradish peroxidase-labeled is formed immune multiple with the syphilis antibody 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 syphilis antibody.

It is an advantage of the invention that its close position relies on electromagnetism adhesive strength set in the terminal of the micro-fluidic chip The described chain ring type magnetic holding device of positioning is connect, is installed with institute's attaching in the chain ring type magnetic holding device one magnetic conductivity link micro- Type ultrasonic transducer, the low-power launched using it, the ultrasonic wave of high-frequency band so that without surface chemical modification or It is compatible between strong hydrophobic its tube wall of micro-fluidic chip internal pipeline and the test object aqueous solution of surface chemical modification Property be significantly increased, this is sample liquid stream by providing a realistic possibility；Meanwhile utilize dimethyl silicone polymer substrate Its strong absorbability to ultrasonic wave, in shorter distance, it is, from the terminal to the sample introduction end In the very short distance of only several centimeters yardsticks, reach the rapid decrement of ultrasonic intensity, thereby described in the micro-fluidic chip The difference of the interfacial tension is caused at both ends, and then, using the interfacial tension between the both ends difference its formed this two Pressure gap between end, driving sample liquid stream is in the strong hydrophobic capillary channel of such a script to the terminal side To flowing.By this case liquid stream drive scheme, entirely without must be to the substrate and its internal pipeline of the dimethyl silicone polymer material Any surface chemical modification or chemical modification are carried out, has altogether dispensed with the trouble journey of the surface chemical modification or chemical modification Sequence；And the equipment of traditional Micropump etc is altogether dispensed with；On the other hand, the low-power, the ultrasound of high-frequency band Ripple, additionally it is possible to contain large biological molecule in sample in literalness naked its inner surface of pipeline of dimethyl silicone polymer substrate On absorption, and then contain the swallow up effect of its body phase of dimethyl silicone polymer substrate to the large biological molecule；It is described anti- Former, antibody and the Reversible binding thing of antigen and antibody are all the type for belonging to described large biological molecule certainly；Due to described Suction-operated and the described effect of swallowing up effectively contained that therefore, dependence test result will be better able to objectively anti- Reflect actual conditions；The effect of the low-power, high-frequency band ultrasonic wave, also include facilitating the reversible knot between antigen, antibody certainly Close the quick of reaction to reach, this causes dependence test operation can be with than the completion of 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 to micro- at this It is prepared by fluidic chip, production, using etc. field play bigger effect.

Attached in the chain ring type magnetic holding device one magnetic conductivity link in this case structure it is fixed installed it is described miniature Ultrasonic transducer, this architecture provides a function of facilitating the device to disassemble, in this way, the chain ring type magnetic holding device is together with it The miniature ultrasonic transducer units attached in one magnetic conductivity link just easily can be mutually disengaged with the micro-fluidic chip, that , the component that the part can freely depart from reuses many times in which just can circulate benignly；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 device embodiment chip part construction, it is shown that the vertical view of this structure The structural form of chip internal pipeline and each electrode and each related liquid pool under angle, the chain ring type is not depicted in the figure Magnetic holding device and the miniature ultrasonic transducer units set up thereon and other annexes.

Fig. 2 be this case device chain ring type magnetic holding device its with appearance side rough under the micro-fluidic chip socket state View, the legend and indicates the relative position relation under the socket state between each component.

Fig. 3 is the outside side view under another viewing angle of this case device；Fig. 3 viewing angle and Fig. 2's Viewing angle is mutually perpendicular to.

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 antigenic substance in the gold size sensitivity membrane structure of top layer is syphilis specific antigen TP0684,6 be installing The specific antigenic substance in its top layer gold size sensitivity membrane structure in lateral 7 is syphilis specific antigen TP0453's Working electrode, 12 be that specific antigenic substance in its top layer gold size sensitivity membrane structure being installed in lateral 11 is syphilis Specific antigen TP0821 working electrode, 13 be the spy in its top layer gold size sensitivity membrane structure being installed in lateral 14 Specific Antigen material is syphilis specific antigen TP0319 working electrode, and 8 be to electrode, and 9 be reference electrode, and 15 be chain ring type Magnetic holding device, 16 be the terminal of the micro-fluidic chip, and 17 be the sample introduction end of the micro-fluidic chip, and 18 be poly dimethyl The substrate of siloxanes material, 19 be cover plate, and 20 be miniature ultrasonic transducer units, and 21 be higher-order of oscillation electric signal transmission cable, 22, 29 be the link of two magnetic conductivity materials positioned at different structure position respectively, and the link of two magnetic conductivity materials is in the structure In end-to-end relation each other, 23,32 be two pole shoes positioned at different structure position respectively, and 24,26,28,31,34,36 are respectively Six pin joints in six diverse locations, 25,27,33,35 be four non magnetic materials in four diverse locations respectively The link of matter, 30 be magnet exciting coil；The chain ring type magnetic holding device structure in legend is only the legend structure of signal, actually the chain Ring type magnetic holding device structure is not limited to the legend chain ring type magnetic holding device structure；Arrow in legend indicates the micro-fluidic core Piece its in actual motion, by pressure at two ends difference drive, the flow direction of its sample liquid stream.

Embodiment

In this case that Fig. 1, Fig. 2 and Fig. 3 are shown embodiment, the structure of the device includes multichannel micro-fluidic core Piece, the structure of the micro-fluidic chip include being bonded to each other the substrate 18 and cover plate 19 of installing together, the substrate 18 and cover plate 19 be plate object or tablet, and that face towards the cover plate 19 of the substrate 18 is contained via mould pressing process or etching technics The channel structure of formation, the substrate 18 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 18 being installed together and the cover plate 19 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 18 is bonded to each other with the cover plate 19, its side of the window Blocked and opposite side opening by the cover plate 19, 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 17 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 16 that liquid flows in chip, the terminal 16 is located remotely from each other with the sample introduction end 17, 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 17 and the UNICOM of liquid pool 2 The other end of pipeline and a remaining liquid pool for the terminal 16 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 antigen 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 antigen in the gold size sensitivity membrane structure of top layer is the four kinds of Treponema pallidum antigen things that can be specifically bound to syphilis antibody respectively Matter, four kinds of antigenic substances are syphilis specific antigen TP0684, TP0453, TP0821 and TP0319 respectively, are specifically deployed For, 5 be that specific antigenic substance in its top layer gold size sensitivity membrane structure being installed in lateral 4 is syphilis specific Antigen TP0684 working electrode, 6 be the specific antigen in its top layer gold size sensitivity membrane structure being installed in lateral 7 Material is syphilis specific antigen TP0453 working electrode, and 12 be its top layer gold size sensitive membrane being installed in lateral 11 The working electrode that specific antigenic substance in structure is syphilis specific antigen TP0821,13 are installed in lateral 14 Its top layer gold size sensitivity membrane structure in specific antigenic substance be syphilis specific antigen 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 18 is dimethyl silicone polymer material, and its surface of substrate 18 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 chain ring type magnetic holding device 15, and six are shared in its structure of the chain ring type magnetic holding device 15 Individual link 22,25,27,29,33,35, the link 22,25,27,29,33,35 is in strip, shaft-like or bar-shaped, each adjacent ring Section is hinged to form chain link, the hexagonal cyclic structure of its appearance profile of the chain link, each top of the hexagonal annular structure Angle is that drift angle 24,26,28,31,34,36 its locations of structures is articulated structure position, the hexagonal annular structure therein two The individual link in opposite side position is that link 22,29 its material is magnetic conductivity material, the remainder of the hexagonal annular structure four Link be link 25,27,33,35, its material be non-magnetic material, the non magnetic material refers to not having to externally-applied magnetic field The material responded strongly, two links of the magnetic conductivity material are that a link among link 22,29 is wound in link 29 There is magnet exciting coil 30, the link 29 for being wound with magnet exciting coil 30 is respectively equiped with the both sides neighbor positions of its magnet exciting coil 30 The pole shoe of one magnetic conductivity material, two pole shoes are shared, the pole shoe is pole shoe 23 and pole shoe 32, and two pole shoes are pole Boots 23 and pole shoe 32 are directed to the link 22 of another magnetic conductivity material, on its surface of the link 22 of another magnetic conductivity material Attach the fixed chain ring type magnetic holding device 15 socket positioning for being equiped with miniature ultrasonic transducer units 20, relying on electromagnetism adhesive strength The close position of its terminal 16 in the micro-fluidic chip, and, higher-order of oscillation electric signal transmission cable 21, the higher-order of oscillation One end of electric signal transmission cable 21 links together with the miniature ultrasonic transducer units 20；The chain ring type magnetic holding device 15 provides One facilitates the function that the device is disassembled；Its major function of the miniature ultrasonic transducer units 20 be micro-fluidic chip it is actual enter When sample is tested, the ultrasonic wave launched using it reduces the interfacial tension between sample solution and the inwall of the pipeline, makes It can be compatible, also, utilizes the sample introduction end 17 and the terminal 16 and the installation position of miniature ultrasonic transducer units 20 The distance between difference on difference and its ultrasonic intensity experienced, its interface of sample introduction end 17 described in induced synthesis Difference between power and the terminal 16 its interfacial tension, the micro-fluidic chip both ends are between sample introduction end 17 and terminal 16 Interfacial tension difference can be to form pressure gap between sample introduction end 17 and terminal 16 at the both ends of the micro-fluidic chip, the pressure Difference can drive sample solution to be flowed to the direction of terminal 16；Its function of the miniature ultrasonic transducer units 20 also includes with its institute The ultrasonic wave of transmitting checks in sample contained its absorption on the inner surface of pipeline of large biological molecule, and then checks this Swallow up effect of its body phase of the substrate 18 of dimethyl silicone polymer material to the large biological molecule；The dimethyl silicone polymer material The substrate 18 of matter its function includes and cover plate 19 and working electrode 5, working electrode 6, working electrode 12, working electrode 13 and to electricity Pole 8 and reference electrode 9 together build the micro-fluidic chip, the substrate 18 of the dimethyl silicone polymer material that is soft and having elasticity Its function is also included with its property to the strong absorption of ultrasonic wave, and ultrasonic wave is absorbed strongly, and thereby micro-fluidic at this The chip terminal 16 is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 17, its structure Position is located at a remaining liquid pool for the terminal of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested Also referred to as terminal liquid pool, the terminal liquid pool is interior to be filled with some high hydroscopic resin particles, and its opening end of terminal liquid pool is by ventilative micro- Pore membrane is covered.

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.

The chain ring type magnetic holding device 15 is depicted without in Fig. 1 and attaches fixation in one magnetic conductivity material link Miniature ultrasonic transducer units 20 and higher-order of oscillation electric signal transmission cable 21 of installing；Also, in Fig. 1, Fig. 2 and Fig. 3 It is depicted without the associate members such as the higher-order of oscillation electric signal generator and multiple tracks electrochemical workstation.

Involved magnetic conductive material and involved nonmagnetic substance market are on sale.

Involved miniature ultrasonic transducer units 20 are commercially available；It can also be customized to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal transmission cable 21 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.

This case device is that a variety of corresponding syphilis antibodies are detected with a variety of Treponema pallidum antigens, thereby Diagnosis of Syphilis.

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 (10)

1. the controller used in syphilis diagnosis device that sample driving can be removed fast with function element, the structure of the device includes multichannel miniflow Chip is controlled, the structure of the micro-fluidic chip includes being bonded to each other the substrate and cover plate of installing together, and the substrate and cover plate are equal For plate object or tablet, the groove via mould pressing process or etching technics formation is contained in that face towards the cover plate of the substrate Road structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or letter The window structure that single drilling technology is formed, it is bonded to each other the substrate being installed together and has been built into jointly containing pipe with the cover plate The micro-fluidic chip of road structure and the liquid pool structure being attached thereto, the locations of structures of the pipeline are located at the substrate and the cover plate phase The interface zone being mutually bonded, 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 institute The locations of structures of liquid pool is stated, the quantity of the liquid pool is three, and its locations of structures of two liquid pools therein is located at the micro-fluidic core The sample introduction end of piece, liquid in its chip when its locations of structures of a remaining liquid pool is located at the test of the micro-fluidic chip actual sample introduction The terminal of flowing, the terminal are located remotely from each other with the sample introduction end, and one end of the pipeline is via being similarly positioned in the interface being bonded to each other The manifold shape turnout in region is micro-fluidic with being located at this with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline respectively A remaining liquid pool UNICOM for the terminal of chip, and, sequentially it is respectively installed in the pipeline on diverse location Working electrode and to electrode and reference electrode, the working electrode is by conductive electrode and is attached to the conductive electrode On embedded syphilis specific antibody gold size sensitive membrane form, the construction of the pipeline is in parallel construction, and described is in structure in parallel The pipeline made is made up of four lateral parallel connections, and the quantity of the working electrode is four, the installing of four working electrodes Position is located in four laterals respectively, and, the spy in its top layer gold size sensitivity membrane structure of four working electrodes Specific Antigen is the four kinds of Treponema pallidum antigen materials that can be specifically bound to syphilis antibody respectively, and four kinds of antigenic substances are plum respectively Malicious specific antigen TP0684, TP0453, TP0821 and TP0319, its material of the working electrode are gold material or thermal decomposition Sheet or thread is presented in conducting polymer material, its pattern of the working electrode, it is characterised in that its material of the substrate is poly- two Methylsiloxane material, its surface of the substrate are the surfaces of primary form, the surface of the primary form its be intended to refer to and do not have By any surface chemical modification or the surface of the primary form of the material of any surface chemical modification, the structure of the device is also Including chain ring type magnetic holding device, six links are shared in its structure of the chain ring type magnetic holding device, the link is in strip, shaft-like Or it is bar-shaped, each adjacent link is hinged to form chain link, the hexagonal cyclic structure of its appearance profile of the chain link, the hexagonal rings Its locations of structures of each drift angle of shape structure is articulated structure position, and two therein of the hexagonal annular structure is in opposite side Its material of the link of position is magnetic conductivity material, and its material of the remaining four processes of the hexagonal annular structure is non magnetic material Matter, the non magnetic material refer to the material not responded strongly to externally-applied magnetic field, two links of the magnetic conductivity material it In a link on be wound with magnet exciting coil, this is wound with both sides neighbor positions of the link in its magnet exciting coil of magnet exciting coil On be respectively equiped with the pole shoe of a magnetic conductivity material, share two pole shoes, two pole shoes are directed to another magnetic conductivity The link of material, fixation is attached on its surface of the link of another magnetic conductivity material and is equiped with miniature ultrasonic transducer units, according to The chain ring type magnetic holding device socket of support electromagnetism adhesive strength is positioned at the close position of its terminal of the micro-fluidic chip, 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 chain ring type magnetic holding device provides a function of facilitating the device to disassemble；The miniature ultrasonic transducer units Its major function is in the test of micro-fluidic chip actual sample introduction, and the ultrasonic wave launched using it reduces sample solution and institute The interfacial tension between the inwall of pipeline is stated, can be compatible, also, it is micro- with this using the sample introduction end and the terminal Difference in the distance between type ultrasonic transducer installation position difference and its ultrasonic intensity experienced, induce shape Difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension, between the micro-fluidic chip both ends Interfacial tension difference can form pressure gap between the both ends of the micro-fluidic chip, and 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 Its absorption on the inner surface of pipeline of some large biological molecules, so check the dimethyl silicone polymer material substrate its Swallow up effect of the body phase to the large biological molecule；Its function of the substrate of the dimethyl silicone polymer material includes and cover plate and work Make electrode and the micro-fluidic chip is together built to electrode and reference electrode, the dimethyl silicone polymer material that is soft and having elasticity Its function of the substrate of matter also includes with its property to the strong absorption of ultrasonic wave, and ultrasonic wave is absorbed strongly, and thereby exists The micro-fluidic chip terminal to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end, its Locations of structures is located at described remaining one of the terminal that liquid flows in its chip when the actual sample introduction of the micro-fluidic chip is tested Liquid pool 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 saturating Gas microporous barrier is covered.

2. the controller used in syphilis diagnosis device that sample driving according to claim 1 can be removed fast with function element, its feature It is, the pipeline and the lateral and the manifold shape turnout are capillary channel.

3. the controller used in syphilis diagnosis device that sample driving according to claim 1 can be removed fast with function element, 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 controller used in syphilis diagnosis device that sample driving according to claim 1 can be removed fast with function element, 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 controller used in syphilis diagnosis device that sample driving according to claim 1 can be removed fast with function element, its feature It is, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.

6. the controller used in syphilis diagnosis device that sample driving according to claim 1 can be removed fast with function element, its feature It is, the cover plate its material in structure is dimethyl silicone polymer material.

7. the controller used in syphilis diagnosis device that sample driving according to claim 1 can be removed fast with function element, 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 controller used in syphilis diagnosis device that sample driving according to claim 1 can be removed fast with function element, 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 controller used in syphilis diagnosis device that sample driving according to claim 1 can be removed fast with function element, its feature It is, the structure of the device also includes higher-order of oscillation electric signal generator, and its is another for the higher-order of oscillation electric signal transmission cable End is connected with the higher-order of oscillation electric signal generator.

10. the controller used in syphilis diagnosis device that sample driving according to claim 1 can be removed fast with function element, its feature It is, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 5 milliwatts and 9000 milliwatts, the miniature ultrasonic The frequency of its ultrasonic wave operationally launched of wave transducer is between 100KHz and 12MHz.