CN106153910A - Selected strong hydrophobic PDMS is as the controller used in syphilis diagnosis chip apparatus of substrate material - Google Patents

Abstract

The present invention relates to a kind of selected strong hydrophobic PDMS as the controller used in syphilis diagnosis chip apparatus of substrate material, belong to analysis field tests.There are some difficult problems to the substrate making controller used in syphilis diagnosis micro-fluidic chip with the polydimethylsiloxane i.e. PDMS inexpensively and easily processed；Its surface of this PDMS material is the most hydrophobic, and surface modification or surface are modified targetedly, and its effect is difficult to persistently, and this case aims to solve the problem that this series relevant issues.This case is characterized by, the PDMS with ecosystem surface selected by substrate, and the hinge-type fixture being attached to miniature ultrasonic transducer units manually fastened sample its neighbor positions of liquid stream terminal being positioned at this micro-fluidic chip, interfacial tension is reduced with ultrasound wave, utilize the PDMS strong absorbability to ultrasound wave simultaneously, reach ultrasonic intensity rapid decrement in short distance, thus interfacial tension difference is formed at the two ends of this chip, thereby facilitate sample liquid stream to flow along the most hydrophobic capillary channel to this terminal direction.

Description

Selected strong hydrophobic PDMS is as the controller used in syphilis diagnosis chip apparatus of substrate material

Technical field

The present invention relates to a kind of selected strong hydrophobic PDMS controller used in syphilis diagnosis chip apparatus as substrate material, belong to analysis test Field.

Background technology

Associated multi-channel micro-fluidic controller used in syphilis diagnosis technical background, may refer to the applications for a patent for invention such as CN 200910160439.X Case.

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

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

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

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

But, thing is really not so simply.

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

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

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

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

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

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

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

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

Summary of the invention

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

The present invention solves described technical problem by following scheme, and the device that the program provides is that a kind of selected strong hydrophobic PDMS makees For the controller used in syphilis diagnosis chip apparatus of substrate material, the structure of this device includes multichannel micro-fluidic chip, this micro-fluidic chip Structure includes bonded to each other being installed in substrate together and cover plate, and described substrate and cover plate are plate object or tablet, this substrate That face towards this cover plate contain the channel structure formed via mould pressing process or etching technics, this substrate possibly together with this groove Road structure is connected and pierces the window structure formed via mould pressing process, etching technics or simple drilling technology of this substrate, phase It is jointly mounted to this substrate together and this cover plate mutually be jointly built into containing pipeline configuration and the liquid pool structure that is attached thereto Micro-fluidic chip, the locations of structures of this pipeline is positioned at the interface zone that this substrate is bonded to each other with this cover plate, its side of this window Being blocked by this cover plate and opposite side opening, the locations of structures of this window is exactly the locations of structures of described liquid pool, the quantity of described liquid pool Being three, two its locations of structures of liquid pool therein are positioned at the sample introduction end of this micro-fluidic chip, remaining its structure position of a liquid pool The terminal of liquid flowing in its chip when testing setting in the actual sample introduction of this micro-fluidic chip, this terminal is the most remote with this sample introduction end From, one end of this pipeline via be similarly positioned in the manifold shape turnout of this interface zone bonded to each other respectively be positioned at sample introduction end should Liang Ge liquid pool UNICOM, this remaining liquid pool UNICOM of the other end of this pipeline and the described terminal being positioned at this micro-fluidic chip, And, the working electrode that is sequentially respectively installed in this pipeline on diverse location and to electrode and reference electrode, described work Electrode is made up of conductive electrode and the gold size sensitive membrane having embedded syphilis specific antigen that is attached on this conductive electrode, The structure of this pipeline is parallel construction, and the described pipeline in parallel construction is made up of four lateral parallel connections, described working electrode Quantity be four, the installation position of these four working electrodes lays respectively in described four laterals, and, these four works Making the specific antigen in its top layer gold size sensitive membrane structure of electrode is the four kind syphilis specific binding to syphilis antibody energy respectively Antigenic substance, these four kinds of antigenic substances are syphilis specific antigen TP0684, TP0453, TP0821 and TP0319 respectively, institute Stating its material of working electrode is gold material or thermal decomposition conducting polymer material, and its pattern of described working electrode presents lamellar or silk Shape, it is important that, its material of this substrate is polydimethylsiloxane material, and its surface of this substrate is the surface of primary form, and this is former The surface of raw form its be intended to refer to not through this material former of any surface chemical modification or any surface chemical modification The surface of raw form, the structure of this device also includes hinge-type fixture, this its appearance profile of hinge-type fixture likeness in form hinge, this conjunction Page fixture by two hinges being mutually hinged and run through one of these two hinges fastening screw and one with should Fastening screw coupling the nut for manually fastening and hand break loose being connected together with this fastening turnbuckle are constituted, this hinge-type This micro-fluidic chip is respectively mutually drawn close and clamp to two hinges of fixture with its tip, and described tip is positioned at this micro-fluidic chip In the locations of structures of neighbouring described terminal, in a described hinge at least in, attaching is fixing is equiped with miniature ultrasonic transducing Device, and, higher-order of oscillation electric signal transmission cable, one end of this higher-order of oscillation electric signal transmission cable is changed with this miniature ultrasonic Can link together by device；This hinge-type fixture provides a function facilitating this device to disassemble；This miniature ultrasonic transducer units its Major function is when the actual sample introduction of micro-fluidic chip is tested, and utilizes its ultrasound wave launched to reduce sample solution and described pipe Interfacial tension between the inwall in road so that it is can be compatible, and, utilize described sample introduction end and described terminal and this miniature super Distance difference between acoustic wave transducer installation position and the difference on its ultrasonic intensity experienced, described in induced synthesis Difference between its interfacial tension of sample introduction end and its interfacial tension of described terminal, the interfacial tension between these two ends of this micro-fluidic chip Difference can form pressure gap between these two ends of this micro-fluidic chip, and this pressure gap can drive sample solution to described terminal Flowing；Its function of this miniature ultrasonic transducer units also includes checking contained in sample biological big point with its ultrasound wave launched Its absorption on described inner surface of pipeline of son, and then its body of substrate checking this polydimethylsiloxane material is big relative to this biology The effect of swallowing up of molecule；Its function of substrate of described polydimethylsiloxane material include with cover plate and working electrode and to electrode and Reference electrode together builds this micro-fluidic chip, and soft and this polydimethylsiloxane material of having elasticity its function of substrate is also wrapped Include with the character of its absorption strong to ultrasound wave, ultrasound wave is absorbed strongly, and thereby arrive in this terminal of this micro-fluidic chip The rapid decrement of ultrasonic intensity is realized within limited short distance between this sample introduction end.

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

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

Described gold size sensitive membrane is chitosan gold size solution and syphilis specific antigenic solution to be sufficiently mixed uniformly, uses point sample instrument Point sample or coat specified structure position, and make its drying and forming-film form.Syphilis specific antigen in described gold size sensitive membrane is equal For horseradish peroxidase or the Treponema pallidum antigen of glucose oxidase labelling, described gold size sensitive membrane be included as fixing above-mentioned respectively Syphilis specific antigen and introduce complementary medium therein, described complementary medium such as chitosan, cellulose acetate, gelatin Therein a kind of or their mixture.

Described pipeline in described microfluidic chip structure and described lateral and described manifold shape turnout, its internal diameter chi Very little may each be arbitrarily selected size, but, for less with the consideration of the aspects such as liquid sample to be measured and reduction reagent loss, Described pipeline and described lateral and described manifold shape turnout the most all select the passage of capillary level, described capillary level Passage imply that the passage that the internal diameter of capillary tube on its internal diameter and ordinary meaning is suitable.Described its inner passage of capillary tube transversal Face shape can be arbitrary shape, described shape of cross section is the most circular, oval, square, rectangle, bar shaped, the most also Can be arbitrary to there is the linear of bending, and, the interior shape of described capillary tube along with the extension of pipeline, different parts Shape of cross section can also allow to be different shapes.Only for capillary tube one word, its art-recognized meanings is known.

Relate in structure is minute sized electrode to electrode and reference electrode, and its electrode shape may each be arbitrarily choosing Fixed shape, described arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..Described to electricity Itself the art-recognized meanings of vocabulary of pole and described reference electrode is known.

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

Only for itself the art-recognized meanings of the ultrasonic transducer one word professional for ultrasonic technology field, it is public Know.

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

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

Only itself micro-channel of naked PDMS substrate is molded or for lithographic technique, be open-and-shut known technology；With Sample ground, the technology of hole-opening known simple technique especially on naked PDMS substrate.This is not launched superfluous words by this case.

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

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

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

The preferred scope of its specified ultrasonic emitting power of this miniature ultrasonic transducer units be between 5 milliwatts and 9000 milliwatts it Between；The preferred scope of the frequency of its ultrasound wave operationally launched of this miniature ultrasonic transducer units be between 100KHz with Between 12MHz.

This case device can further include some adnexaes certainly, described adnexa such as multiple tracks electrochemical workstation etc., institute The art-recognized meanings stating multiple tracks electrochemical workstation is known.Each working electrode of relating in this case microfluidic chip structure and To electrode and reference electrode etc., can be respectively via the most special the corresponding interface got lines crossed with described multiple tracks electrochemical workstation Couple.Described special each the corresponding interface being used to each described electrode with described multiple tracks electrochemical workstation of getting lines crossed is carrying out phase The private cable being mutually coupled with.Described micro-fluidic chip in this case device, its structure can also include micro-valve, the number of described micro-valve Amount does not limits, according to actual needs, and any need position to be mounted that described micro-valve can be installed in this microfluidic chip structure； This micro-valve one word is for the professional of micro fluidic chip technical field, and the art-recognized meanings of itself is known；This micro-valve The manufacturing technology of itself and use technology are also known；This optional component of micro-valve.

The diameter of described working electrode can allow the suitable diameter being easily installed use being arbitrarily set, it is however recommended to Or say preferred its scope of described diameter between 0.1 micron to 2000 micron；The length of described working electrode can permit Permitted the length being easily installed use being arbitrarily set, it is however recommended to or to say preferred its scope of described length be at 1 micron Between 15000 microns.

The described gold size being installed in described working electrode surface layer by spraying or point sample instrument point sample or the coating of other appropriate process is quick Sense film, its thicknesses of layers can allow the thickness that the sample measuring liquid the treated generation electrical signals being arbitrarily set responds, but, push away The thickness recommended the most preferably thickness is between 10 nanometers and 200 nanometers.

Described cover plate in chip structure, its material can allow to be any electrical insulating property material, such as: polypropylene, glass Glass, polymethyl methacrylate, polydimethylsiloxane, etc., in order to make smaller size of micro-fluidic chip, such as do Become the micro-fluidic chip of the super-small of length only 2.0 centimetres to 3.0 centimetres, and realize ultrasound wave in the distance that this is extremely short Extremely fast decay, it may be preferred to polydimethylsiloxane is used as cover plate.Certainly, large-sized micro-fluidic chip selects Use polydimethylsiloxane to be used as described cover plate, be also that this case technical scheme is allowed.

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

Described cover plate and its thickness of substrate can allow the thickness being easy to assembling being arbitrarily set, it is recommended that thickness or say preferably Thickness be between 1.0 millimeters and 5.0 millimeters.Less thickness is conducive to saving material.

The using method of this case micro-fluidic chip:

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

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

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

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

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

2, the syphilis specific antigen of horseradish peroxidase-labeled forms immune complex with the syphilis antibody in blood serum sample.

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

4, result is comprehensively analyzed, syphilis antibody is carried out comprehensive diagnos.

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

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

The technical scheme of this case has dissolved relevant to its application of polydimethylsiloxane substrate addressed above totally Row technical barrier.Based on this case scheme, the most cheap polydimethyl siloxane material of this kind is the most likely at this micro-fluidic chip Prepare, produce, application etc. field plays bigger effect.

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

Accompanying drawing explanation

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

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

In figure, 1,2,10 is the liquid pool that three installation positions are different respectively, and 3 is manifold shape turnout, 4,7,11,14 Being installation position difference respectively but four laterals forming UNICOM in parallel structure parallel with one another, 5 is to be installed in lateral 4 The interior working electrode that specific antigenic substance is syphilis specific antigen TP0684 in its top layer gold size sensitive membrane structure, 6 Be the specific antigenic substance in its top layer gold size sensitive membrane structure being installed in lateral 7 be syphilis specific antigen The working electrode of TP0453,12 is the specific antigen in its top layer gold size sensitive membrane structure being installed in lateral 11 Material is the working electrode of syphilis specific antigen TP0821, and 13 is that its top layer gold size being installed in lateral 14 is sensitive Specific antigenic substance in membrane structure is the working electrode of syphilis specific antigen TP0319, and 8 is to electrode, and 9 is reference electricity Pole, 15 is hinge-type fixture, and 16 indicate linkwork position, and 17 is fastening screw, and 18 is higher-order of oscillation electric signal Transmission cable, 19 is miniature ultrasonic transducer units, and 20,25 is two hinges that locations of structures is different respectively, and 21 is cover plate, 22 is substrate, and 23 is sample introduction end, and 24 is terminal, and 26 is nut；This hinge-type clamp structure in legend is only signal Legend structure, this its structure of hinge-type fixture actual is not limited to this legend hinge-type clamp structure；Arrow in legend indicates This micro-fluidic chip its when actual motion, driven by pressure at two ends difference, the flow direction of its sample liquid stream.

Detailed description of the invention

In this embodiment of this case that Fig. 1 and Fig. 2 is shown, the structure of this device includes multichannel micro-fluidic chip, and this is micro- The structure of fluidic chip includes bonded to each other being installed in substrate 22 together and cover plate 21, and described substrate 22 and cover plate 21 are Plate object or tablet, that face towards this cover plate 21 of this substrate 22 is contained and is formed via mould pressing process or etching technics Channel structure, this substrate 22 possibly together be connected with this channel structure and pierce this substrate via mould pressing process, etching technics Or the window structure that simply drilling technology is formed, this substrate 22 being installed together bonded to each other is built into jointly with this cover plate 21 Containing pipeline configuration and the micro-fluidic chip of liquid pool structure that is attached thereto, described liquid pool is liquid pool 1, liquid pool 2, liquid pool 10, the locations of structures of this pipeline is positioned at the interface zone that this substrate 22 is bonded to each other with this cover plate 21, and its side of this window is by this Cover plate 21 blocks and opposite side is open, and the locations of structures of this window is exactly the structure position of described liquid pool 1, liquid pool 2, liquid pool 10 Putting, the quantity of described liquid pool is three, and the i.e. liquid pool 1 of two liquid pools therein and its locations of structures of liquid pool 2 are positioned at this micro-fluidic core The sample introduction end 23 of sheet, a remaining liquid pool i.e. its locations of structures of liquid pool 10 be positioned at this micro-fluidic chip actual sample introduction test time its The terminal 24 of liquid flowing in chip, this terminal 24 is located remotely from each other with this sample introduction end 23, and one end of this pipeline is via same position In the manifold shape turnout 3 of this interface zone bonded to each other respectively be positioned at this liquid pool 1 and this liquid pool 2 UNICOM of sample introduction end 23, This remaining liquid pool i.e. liquid pool 10 UNICOM of the other end of this pipeline and the described terminal 24 being positioned at this micro-fluidic chip, with And, the working electrode that is sequentially respectively installed in this pipeline on diverse location and to electrode 8 and reference electrode 9, described work Make electrode by conductive electrode and the gold size sensitive membrane structure having embedded syphilis specific antigen that is attached on this conductive electrode Becoming, the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is made up of four lateral parallel connections, described work The quantity of electrode is four, and the installation position of these four working electrodes lays respectively in described four laterals, these four work Electrode is working electrode 5, working electrode 6, working electrode 12, working electrode 13 respectively, and, these four working electrodes its Specific antigen in the gold size sensitive membrane structure of top layer is four kinds of Treponema pallidum antigen materials that can be specific binding to syphilis antibody respectively, These four kinds of antigenic substances are syphilis specific antigen TP0684, TP0453, TP0821 and TP0319 respectively, specifically launch to come Say, 5 be the specific antigenic substance in its top layer gold size sensitive membrane structure being installed in lateral 4 be syphilis specific resist The working electrode of former TP0684,6 is the specific antigen in its top layer gold size sensitive membrane structure being installed in lateral 7 Material is the working electrode of syphilis specific antigen TP0453, and 12 is that its top layer gold size being installed in lateral 11 is sensitive Specific antigenic substance in membrane structure is the working electrode of syphilis specific antigen TP0821, and 13 is to be installed in lateral 14 The interior working electrode that specific antigenic substance is syphilis specific antigen TP0319 in its top layer gold size sensitive membrane structure, institute State working electrode 5, working electrode 6, working electrode 12, its material of working electrode 13 are gold material or thermal decomposition conduction height Molecule material, described working electrode 5, working electrode 6, working electrode 12, its pattern of working electrode 13 present lamellar or silk Shape, it is important that, this its material of substrate 22 is polydimethylsiloxane material, and this its surface of substrate 22 is the table of primary form Face, the surface of this primary form its be intended to refer to not through this material of any surface chemical modification or any surface chemical modification The surface of the primary form of matter, the structure of this device also includes hinge-type fixture 15, its appearance profile shape of this hinge-type fixture 15 Like hinge, this hinge-type fixture 15 by two hinges 20,25 being mutually hinged and run through these two hinges 20, One fastening screw 17 of 25 and the use mated with this fastening screw 17 and connect together with this fastening screw 17 Nut 26 in manually fastening and hand break loose is constituted, and two hinges 20,25 of this hinge-type fixture 15 are each with its tip phase Drawing close and clamp this micro-fluidic chip mutually, described tip is positioned at the locations of structures of the neighbouring described terminal 24 of this micro-fluidic chip On, a described hinge at least in attaches fixing being equiped with in miniature ultrasonic transducer units, this legend, is in hinge Attach on 20 and install this miniature ultrasonic transducer units 19, it is of course also possible to allow all to install in two hinges 20,25 Miniature ultrasonic transducer units, but, it is, in general, that only attach one miniature ultrasonic transducer units of installing in a described hinge Just be enough to deal be actually needed, and, higher-order of oscillation electric signal transmission cable 18, this higher-order of oscillation electric signal transmission cable 18 One end link together with this miniature ultrasonic transducer units 19；This hinge-type fixture 15 provides one and facilitates this device to tear open The function solved；This its major function of miniature ultrasonic transducer units 19 is when the actual sample introduction of micro-fluidic chip is tested, and utilizes its institute The ultrasound wave launched reduces the interfacial tension between the inwall of sample solution and described pipeline so that it is can be compatible, and, profit By the distance difference between described sample introduction end 23 and described terminal 24 and this miniature ultrasonic transducer units 19 installation position and Difference on its ultrasonic intensity experienced, its interfacial tension of sample introduction end 23 described in induced synthesis and described terminal 24 its Difference between interfacial tension, these two ends of this micro-fluidic chip i.e. interfacial tension difference meeting between sample introduction end 23 and terminal 24 I.e. form pressure gap between sample introduction end 23 and terminal 24 at these two ends of this micro-fluidic chip, this pressure gap can drive examination Sample solution flows to described terminal 24 direction；This its function of miniature ultrasonic transducer units 19 also include with its launched ultrasonic Ripple checks its absorption on described inner surface of pipeline of biomacromolecule contained in sample, and then checks this polydimethylsiloxanes Its body of substrate 22 of alkane material is relative to the effect of swallowing up of this biomacromolecule；The substrate 22 of described polydimethylsiloxane material Its function include with cover plate 21 and working electrode 5, working electrode 6, working electrode 12, working electrode 13 and to electrode 8 and Reference electrode 9 together builds this micro-fluidic chip, soft and have its merit of substrate 22 of this polydimethylsiloxane material of elasticity Can also include, with the character of its absorption strong to ultrasound wave, ultrasound wave being absorbed strongly, and thereby should at this micro-fluidic chip Terminal 24 is to the rapid decrement realizing ultrasonic intensity within the limited short distance between this sample introduction end 23.

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

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

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

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

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

Each working electrode in this example structure and can be respectively via the most special cable or say to electrode and reference electrode Get lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as adnexa or say interface of getting lines crossed and couple.

This case device is to detect multiple corresponding syphilis antibody, thereby Diagnosis of Syphilis with multiple Treponema pallidum antigen.

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

Claims (10)

1. selecting the strong hydrophobic PDMS controller used in syphilis diagnosis chip apparatus as substrate material, the structure of this device includes multichannel miniflow Control chip, the structure of this micro-fluidic chip includes bonded to each other being installed in substrate together and cover plate, and described substrate and cover plate are Plate object or tablet, the conduit knot formed via mould pressing process or etching technics is contained in that face towards this cover plate of this substrate Structure, this substrate is possibly together with being connected with this channel structure and piercing via mould pressing process, etching technics or simply punching of this substrate The window structure that technique is formed, this substrate being installed together bonded to each other and this cover plate be jointly built into containing pipeline configuration with And the micro-fluidic chip of the liquid pool structure being attached thereto, the locations of structures of this pipeline is positioned at the boundary that this substrate is bonded to each other with this cover plate Region, face, its side of this window is blocked by this cover plate and opposite side is open, and the locations of structures of this window is exactly the structure of described liquid pool Position, the quantity of described liquid pool is three, and two its locations of structures of liquid pool therein are positioned at the sample introduction end of this micro-fluidic chip, remaining Under its locations of structures of liquid pool terminal of its chip liquid flowing when being positioned at the test of this micro-fluidic chip actual sample introduction, this is eventually End is located remotely from each other with this sample introduction end, and one end of this pipeline is divided via the manifold shape turnout being similarly positioned in this interface zone bonded to each other Not be positioned at this Liang Ge liquid pool UNICOM of sample introduction end, the other end of this pipeline is remaining with this of described terminal being positioned at this micro-fluidic chip Under a liquid pool UNICOM, and, the working electrode that is sequentially respectively installed in this pipeline on diverse location and to electrode and Reference electrode, described working electrode by conductive electrode and be attached on this conductive electrode embedded syphilis specific antibody Gold size sensitive membrane constitute, the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is by four lateral parallel connections Constituting, the quantity of described working electrode is four, and the installation position of these four working electrodes lays respectively at described four laterals In, and, the specific antigen in its top layer gold size sensitive membrane structure of these four working electrodes is can be special to syphilis antibody respectively Property combine four kinds of Treponema pallidum antigen materials, these four kinds of antigenic substances are syphilis specific antigen TP0684, TP0453, TP0821 respectively And TP0319, its material of described working electrode is gold material or thermal decomposition conducting polymer material, its pattern of described working electrode Presenting lamellar or thread, it is characterised in that its material of this substrate is polydimethylsiloxane material, its surface of this substrate is primary The surface of form, the surface of this primary form its be intended to refer to not change through any surface chemical modification or any surface chemistry The surface of the primary form of this material of property, the structure of this device also includes hinge-type fixture, this its appearance profile of hinge-type fixture Likeness in form hinge, this hinge-type fixture is by two hinges being mutually hinged and the fastening screw running through these two hinges And one mate with this fastening screw and with this fastening turnbuckle be connected together for manually fastening and the nut of hand break loose Constituting, this micro-fluidic chip is respectively mutually drawn close and clamp to two hinges of this hinge-type fixture with its tip, and described tip is positioned at In the locations of structures of the neighbouring described terminal of this micro-fluidic chip, a described hinge at least in attaches fixing being equiped with Miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, one end of this higher-order of oscillation electric signal transmission cable with This miniature ultrasonic transducer units links together；This hinge-type fixture provides a function facilitating this device to disassemble；This is miniature Its major function of ultrasonic transducer is when the actual sample introduction of micro-fluidic chip is tested, and utilizes its ultrasound wave launched to reduce examination Interfacial tension between the inwall of sample solution and described pipeline so that it is can be compatible, and, utilize described sample introduction end and described Distance difference between terminal and this miniature ultrasonic transducer units installation position and the difference on its ultrasonic intensity experienced Different, difference between its interfacial tension of sample introduction end and its interfacial tension of described terminal described in induced synthesis, this micro-fluidic chip this two Interfacial tension difference between end can form pressure gap between these two ends of this micro-fluidic chip, and this pressure gap can drive examination Sample solution is to described end flow；Its function of this miniature ultrasonic transducer units also includes checking in sample with its ultrasound wave launched Contained its absorption on described inner surface of pipeline of biomacromolecule, and then check the substrate of this polydimethylsiloxane material Its body is relative to the effect of swallowing up of this biomacromolecule；Its function of substrate of described polydimethylsiloxane material includes and cover plate and work Making electrode and electrode and reference electrode together build this micro-fluidic chip, softness also has this elastic polydimethylsiloxane material Its function of substrate also include, with the character of its absorption strong to ultrasound wave, ultrasound wave being absorbed strongly, and thereby micro-at this This terminal of fluidic chip is to the rapid decrement realizing ultrasonic intensity within the limited short distance between this sample introduction end.

Selected strong hydrophobic PDMS the most according to claim 1 is as the controller used in syphilis diagnosis chip apparatus of substrate material, its feature Being, described pipeline and described lateral and described manifold shape turnout are capillary channel.

Selected strong hydrophobic PDMS the most according to claim 1 is as the controller used in syphilis diagnosis chip apparatus of substrate material, its feature Being, described thermal decomposition conducting polymer is the conductive material formed after anoxybiotic heat treatment by polyimides or polyacrylonitrile.

Selected strong hydrophobic PDMS the most according to claim 1 is as the controller used in syphilis diagnosis chip apparatus of substrate material, its feature Be, the width of described working electrode or diameter between 0.1 micron to 2000 micron, and, described working electrode Length is between 1 micron to 15000 micron.

Selected strong hydrophobic PDMS the most according to claim 1 is as the controller used in syphilis diagnosis chip apparatus of substrate material, its feature Being, the thickness of described gold size sensitive membrane is between 10 nanometers and 200 nanometers.

Selected strong hydrophobic PDMS the most according to claim 1 is as the controller used in syphilis diagnosis chip apparatus of substrate material, its feature Being, its material of described cover plate in structure is polydimethylsiloxane material.

Selected strong hydrophobic PDMS the most according to claim 1 is as the controller used in syphilis diagnosis chip apparatus of substrate material, its feature Be, be positioned at this micro-fluidic chip this sample introduction end these two liquid pools its with to be positioned at this of this this terminal of micro-fluidic chip remaining Air line distance between one liquid pool is between 3 centimetres and 7 centimetres.

Selected strong hydrophobic PDMS the most according to claim 1 is as the controller used in syphilis diagnosis chip apparatus of substrate material, its feature Being, described cover plate in structure and its thickness of substrate are all between 1.0 millimeters and 5.0 millimeters.

Selected strong hydrophobic PDMS the most according to claim 1 is as the controller used in syphilis diagnosis chip apparatus of substrate material, its feature Being, the structure of this device also includes higher-order of oscillation electric signal generator, the described higher-order of oscillation its other end of electric signal transmission cable It is connected with this higher-order of oscillation electric signal generator.

Selected strong hydrophobic PDMS the most according to claim 1 is as the controller used in syphilis diagnosis chip apparatus of substrate material, and it is special Levying and be, its specified ultrasonic emitting power of this miniature ultrasonic transducer units is between 5 milliwatts and 9000 milliwatts, and this is miniature The frequency of its ultrasound wave operationally launched of ultrasonic transducer is between 100KHz and 12MHz.