CN106153930A - The controller used in syphilis diagnosis device that a kind of sample driving adapter can fast remove - Google Patents

Abstract

The present invention relates to the controller used in syphilis diagnosis device that a kind of sample driving adapter can fast remove, belong to analysis field tests.There are some difficult problems with the substrate that dimethyl silicone polymer i.e. PDMS that is cheap and that easily process makes controller used in syphilis diagnosis micro-fluidic chip；Its surface of this PDMS material is strongly 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 elastic clip of miniature ultrasonic transducer units will be attached on its clamping limb with elastic force snap-in location in sample its neighbor positions of liquid flow terminal of this micro-fluidic chip, reduce interfacial tension with ultrasonic wave, utilize the strong absorbability to ultrasonic wave for the PDMS simultaneously, reach ultrasonic intensity rapid decrement in short distance, thus form interfacial tension difference at the two ends of this chip, thereby facilitate sample liquid flow to flow along originally hydrophobic capillary channel to this terminal direction.

Description

The controller used in syphilis diagnosis device that a kind of sample driving adapter can fast remove

Technical field

The present invention relates to the controller used in syphilis diagnosis device that a kind of sample driving adapter can fast remove, belong to analysis field tests.

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 the microflow control technique overall general picture of itself, 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 of the concern of this case to be had a talk below.

The basic framework of micro-fluidic chip, including be etched with the substrate of small fluid course and the cover plate fitting together therewith, Small fluid course on described substrate, before fit on cover plate, apparent on see to be exactly some micro-channel, wait until on it 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 The inner surface state of the micro-channel on piece or inner surface character 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, can act as substrate and the material of cover plate is permissible It is monocrystalline silicon piece, quartz plate, sheet glass, high polymer such as dimethyl silicone polymer, 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 not little difference, the especially selection of that substrate between these materials, impact is relatively Greatly.

Make in material at various substrates, dimethyl silicone polymer, i.e. PDMS, it is very easily molded comparatively speaking, so Substrate on to make micro-channel extremely simple, and this lower cost for material, make substrate with this polydimethyl siloxane material, Compacting or etching micro-channel on it, and match with the cover plate that glass or the cheap material such as polypropylene or other plastic sheets make, It is a kind of more satisfactory selection seemingly；Certainly, patch material also can 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 overall assembling completes, after i.e. covering cover plate, lead to because its inner surface of described micro-channel in structure occupies most liquid flow 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 the aqueous solution the fine liquid flow of polar liquid by becoming very difficult, its flow resistance is big, and even 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, it among prior art, is modified modifying particular for the micro-channel inner surface on this PDMS material, is necessary Operation；So, this is pretty troublesome for the modification operation of PDMS micro-channel inner surface？That is not this problem, structure Become serious technical puzzlement, be another problem: its PDMS polymer molecule tool within body phase of this PDMS material substrate Having the characteristic automatically diffusing to the surface, migrating, the internal PDMS polymer molecule of this substrate body phase 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 that surface modification is modified The enough long time, holding time of its inner surface state of the micro-channel after that is surface-modified is substantially only sufficient to complete in laboratory The time of portion's test experiments needs；In other words, this PDMS micro-channel inner surface modified through surface modification or surface, its After Gai Xing or say the surface state being formed after modification can not be lasting, but automatically tend to soon or say become surface again and change Surface state before property, returns to the strongly hydrophobic surface state 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 flow of polar solvent being similar to the aqueous solution cannot pump Sending and passing through, chip also just cannot use；And if done surface modification, cannot persistently keep again its state after modifying, also It is equally cannot popularization and application.

So, how to accomplish to utilize cheap PDMS material making 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 strongly hydrophobic, this strongly hydrophobic Material surface and also another problem, that is, large biological molecule can be adsorbed in this strongly hydrophobic PDMS surface, and And, the depression that these adsorbed large biological molecules also can be further on PDMS surface further, gradually falls into gradually deep, directly It is trapped within the body phase of PDMS substrate to heavy, in fact, this process, it is partly also due to inside PDMS material body phase Polymer molecule have diffuse to the surface, travel motion is caused；This situation, it is also possible to explain from another angle, i.e. Continuously by inside PDMS body phase to those polymer molecules of its diffusion into the surface, migration, the result of its motion, be by Gradually being involved within the body phase of PDMS substrate by the large biological molecule of adsorption by those, briefly, these are inhaled Attached large biological molecule is swallowed up by PDMS substrate body phase exactly；So, this PDMS substrate body phase swallows up large biological molecule Phenomenon, its impact being caused, necessarily cause the severe deviations relating to all kinds of test data of experiment of large biological molecule.

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

With regard to PDMS substrate in related experiment test process its body mutually constantly swallow up test the big molecule of associated biomolecule phenomenon, separately A kind of explanation is to say, there is substantial amounts of Minute pores in PDMS body phase, the big molecule of associated biomolecule by after 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 large biological molecule 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 Big molecule 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 existing.

In order to stop the effect of swallowing up relative to large biological molecule for this PDMS substrate body, can be from containment PDMS surface to life The absorption of the big molecule of thing 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 modification, Jing Guohua are chemically modified to the surface of described micro-channel part Learn the described micro-channel inner surface of modification, its absorption to large biological molecule can be contained, and then avoid large biological molecule quilt PDMS substrate body phase is swallowed up；But, or that old problem, that is, the chemical modification on PDMS material surface changes Surface state after property cannot persistently keep, this polymer molecule within PDMS substrate body phase its automatically diffuse to the surface, The process migrating, can become that again script strong through the modified micro-channel inner surface state of surface chemical modification soon 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, this PDMS Its micro-channel inner surface of substrate 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, can reach again Growth stage contains this absorption process to large biological molecule for PDMS substrate micro-channel inner surface, and then stops PDMS substrate body phase The effect of swallowing up to large biological molecule so that related chip manufactured goods are able to maintain that a shelf-life enough long, rational, It is exactly a very thorny difficult problem.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 Also having there are a lot of days in topic, up to now, is also not yet properly settled.

Content 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 a kind of sample driving adapter The controller used in syphilis diagnosis device that can fast remove, the structure of this device includes multichannel micro-fluidic chip, the structure of this micro-fluidic chip Including bonded to each other be installed in substrate together and cover plate, described substrate and cover plate are plate object or tablet, the face of this substrate Contain the channel structure being formed via mould pressing process or etching technics to that face of this cover plate, this substrate is tied possibly together with this conduit Structure is connected and pierces the window structure being formed via mould pressing process, etching technics or simple drilling technology of this substrate, mutually pastes That closes that this substrate of being installed together jointly has been built into containing pipeline configuration and the liquid pool structure that is attached thereto with this cover plate is micro- Fluidic chip, the locations of structures of this pipeline is positioned at this substrate interface zone bonded to each other with this cover plate, and its side of this window is by this Cover plate blocks and opposite side is open, and the locations of structures of this window is exactly the locations of structures of described liquid pool, and the quantity of described liquid pool is three Individual, two its locations of structures of liquid pool therein are positioned at the sample introduction end of this micro-fluidic chip, remaining its locations of structures position of a liquid pool The terminal that in its chip, liquid flows when the actual sample introduction of this micro-fluidic chip is tested, this terminal is located remotely from each other with this sample introduction end, should One end of pipeline via be similarly positioned in the manifold shape turnout of this interface zone bonded to each other respectively be positioned at these two of sample introduction end 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 working electrode by Conductive electrode and the gold size sensitive membrane having embedded syphilis specific antigen being attached on this conductive electrode are constituted, this pipeline Construction be parallel construction, the described pipeline in parallel construction is made up of four lateral parallel connections, the quantity of described working electrode Being four, the installation position of this four working electrodes lays respectively in described four laterals, and, this four working electrodes Specific antigen in its top layer gold size sensitive membrane structure is four kinds of Treponema pallidum antigen things that can be specific binding to syphilis antibody respectively Matter, this four kinds of antigenic substances are syphilis specific antigen TP0684, TP0453, TP0821 and TP0319 respectively, described work Its material of electrode is gold material or thermal decomposition conducting polymer material, and its pattern of described working electrode presents sheet or thread, weight Point is that its material of this substrate is dimethyl silicone polymer material, and its surface of this substrate is the surface of primary form, this primary form Surface its be intended to refer to not through the primary form of this material of any surface chemical modification or any surface chemical modification Surface, the structure of this device also includes elastic clip, and two of this elastic clip clamping limb snap-in location in opposite directions is at this micro-fluidic core The position of the neighbouring described terminal of piece, on a described clamping limb 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 and this miniature ultrasonic change Can device link together；This elastic clip provides a function facilitating this device to disassemble；It is main for this miniature ultrasonic transducer units Function is when the actual sample introduction of micro-fluidic chip is tested, and utilizes its ultrasonic wave launched to reduce sample solution and described pipeline Interfacial tension between inwall so that it is can be compatible, and, utilize described sample introduction end and described terminal and this miniature ultrasonic Distance difference between transducer installation position and the difference on its ultrasonic intensity experienced, sample introduction described in induced synthesis Hold the difference between its interfacial tension and its interfacial tension of described terminal, the interfacial tension difference between this two ends of this micro-fluidic chip Can form pressure gap between this two ends of this micro-fluidic chip, this pressure gap can drive sample solution to described terminal stream Dynamic；Its function of this miniature ultrasonic transducer units also includes checking large biological molecule contained in sample with the ultrasonic wave that it is launched Its absorption on described inner surface of pipeline, and then big relative to this biology point of its body of substrate checking this dimethyl silicone polymer material The effect of swallowing up of son；Its function of substrate of described dimethyl silicone polymer material includes and cover plate and working electrode and to electrode and ginseng Together building this micro-fluidic chip than electrode, its function of substrate of softness this dimethyl silicone polymer material having elasticity also includes With the character of its strong absorption to ultrasonic wave, ultrasonic wave is absorbed strongly, and thereby this terminal of this micro-fluidic chip to should The rapid decrement of ultrasonic intensity is realized within limited short distance between sample introduction end.

Described miniature ultrasonic transducer units can certainly be all installed on two clamping limbs；But, only installing one is miniature Ultrasonic transducer has enough been dealt with and has been employed.

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

Described gold size sensitive membrane is to be sufficiently mixed uniformly shitosan gold size solution and syphilis specific antigenic solution, 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 The Treponema pallidum antigen marking for horseradish peroxidase or glucose oxidase, 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 shitosan, 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 as far as possible 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 preferably all select the passage of capillary level, described capillary level Passage imply that the suitable passage of the internal diameter of capillary on its internal diameter and ordinary meaning.Described its inner passage of capillary transversal Face shape can be arbitrary shape, described shape of cross section is for example circular, oval, square, rectangle, bar shaped, certainly also Can be arbitrary to there is the linear of bending, and, the interior shape of described capillary with the extension of pipeline, different parts Shape of cross section also can allow to be different shapes.Only for capillary 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 The art-recognized meanings of pole and the described reference electrode vocabulary of itself is known.

Relating to several liquid pools in this case microfluidic chip structure, described liquid pool is the pond shape or scrotiform structure for transitional liquid storage 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 The hypomegetic liquid pool of coupling.

It only for the professional for ultrasonic technology field for the ultrasonic transducer one word art-recognized meanings of itself, 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 calculating 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 the naked PDMS substrate micro-channel of itself 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 also 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 all 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.

The involved higher-order of oscillation electric signal generator technology of itself, 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 that its specified ultrasonic wave of this miniature ultrasonic transducer units launches power be between 5 milliwatts and 5000 milliwatts it Between；The preferred scope of the frequency of its ultrasonic wave operationally launched of this miniature ultrasonic transducer units be between 100KHz with Between 12MHz.

This case device can further include some annexes certainly, described annex 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 special accordingly 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 and 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 also can 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 microns；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 of the sample measuring liquid the treated generation electrical signals response being arbitrarily set, but, push away The thickness recommended preferred thickness in other words conj.or perhaps is between 10 nanometers and 200 nanometers.

Described cover plate in chip structure, its material can allow to be any electrical insulating property material, for example: polypropylene, glass Glass, polymethyl methacrylate, dimethyl silicone polymer, 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 to ultrasonic wave in this extremely short distance Extremely fast decay, it may be preferred to dimethyl silicone polymer is used as cover plate.Certainly, large-sized micro-fluidic chip selects Use dimethyl silicone polymer 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 this 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 flow driving principle, its application running of this case micro-fluidic chip In, this novel liquid flow driving method determines completely without involving any additional Micropump.

This interfacial tension difference being formed between this two ends of this micro-fluidic chip that this case is caused with described ultrasonic 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 bond, therefore, detect antibody thereby Diagnosis of Syphilis with antigen, and with antibody Remove detecting 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:

1st, adding blood serum sample liquid in micro-pipeline, under described ultrasonic 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.

2nd, the syphilis specific antigen of horseradish peroxidase-labeled and the syphilis antibody in blood serum sample form immune complex.

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

4th, result is carried out comprehensive analysis, comprehensive diagnos is carried out to syphilis antibody.

It is an advantage of the invention that at elastic clip described in its close position snap-in location of described terminal of described micro-fluidic chip, with Attached the miniature ultrasonic transducer units installed on the clamping limb of this elastic clip, utilized its low-power launched, high-frequency band Ultrasonic wave so that without its pipe of this strongly hydrophobic micro-fluidic chip internal pipeline of surface chemical modification or surface chemical modification Wall and test object water solution between compatibility be significantly increased, this for sample liquid flow by providing a realistic possibility； Meanwhile, its strong absorbability to ultrasonic wave of dimethyl silicone polymer substrate is utilized, in comparatively short distance, it is, In the very short distance of the only several centimeters yardstick from described terminal to described sample introduction end, reach the fast express delivery of ultrasonic intensity Subtracting, thereby the difference of described interfacial tension is caused at the described two ends at this micro-fluidic chip, and then, utilize the boundary between this two ends Pressure gap between its this two ends being formed of the difference of surface tension, drives sample liquid flow originally strongly hydrophobic in such a To the flowing of described terminal direction in capillary channel.By this case liquid flow drive scheme, entirely without must be to this dimethyl silicone polymer The substrate of material and internal pipeline thereof carry out any surface chemical modification or chemical modification, have altogether dispensed with this surface chemical modification Or the laborious procedures of chemical modification；And altogether dispense with the equipment of traditional Micropump etc；On the other hand, this low work( Rate, the ultrasonic wave of high-frequency band, additionally it is possible to the large biological molecule in containment sample is at this literalness naked dimethyl silicone polymer Absorption on its inner surface of pipeline of substrate, and then contain gulping down of this dimethyl silicone polymer substrate relatively described large biological molecule of its body No effect；The Reversible binding thing of described antigen, antibody and antigen and antibody is all belonging to the class of described large biological molecule certainly Type；Owing to described suction-operated and the described effect of swallowing up are contained effectively, therefore, dependence test result will more can Enough reflection actual conditions objectively；This low-power, the effect of high-frequency band ultrasonic wave, certainly also include facilitating antigen, antibody it Between Reversible binding reaction quickly reach, this make dependence test operation can be to complete than speed faster.

Owing to not needing to carry out grasping for surface chemical modification or the chemical modification of this dimethyl silicone polymer its relevant surfaces of substrate Making, therefore, this surface chemical modification layer or chemically modified layer not need existence, then, this dimethyl silicone polymer Its body phase interior polymeric thing molecule of substrate constantly diffuses to the surface automatically, migrate it caused to described surface chemical modification layer or The damaging influence of chemically modified layer does not also just exist.

The technical scheme of this case has dissolved related to its application of dimethyl silicone polymer substrate addressing above totally Row technical barrier.Based on this case scheme, the very cheap polydimethyl siloxane material of this kind is just possible at this micro-fluidic chip Preparation, production, application etc. field plays bigger effect.

Fix on its clamping limb of this elastic clip in this case structure and installed described miniature ultrasonic transducer units, this architecture provides One facilitates the function that this device is disassembled, and so, this elastic clip just can facilitate together with miniature ultrasonic transducer units appended on it Ground is mutually disengaged with this micro-fluidic chip, then, the component that this part can freely depart from just can be reused perhaps with circulating benignly Repeatedly；This architectural feature is conducive to saving the use cost of this device.

Brief description

Fig. 1 is the schematic diagram of this device embodiment chip part of this case construction, it is shown that the depression angle of this example structure Under chip internal pipeline and the structural form of each electrode and each related liquid pool, this figure is not depicted described elastic clip and its On the miniature ultrasonic transducer units set up and other described annexes.

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

In figure, the 2nd, 10 being the 1st, the different liquid pool of three installation positions respectively, 3 is manifold shape turnout, the 4th, the 7th, the 11st, 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 specific antigenic substance in its top layer gold size sensitive membrane structure is the working electrode of syphilis specific antigen TP0684,6 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 elastic clip, and the 16th, 21 is two clamping limbs of elastic clip respectively, and 17 is the described terminal of this micro-fluidic chip, 18 is the described sample introduction end of this micro-fluidic chip, and 19 is the substrate of dimethyl silicone polymer material, and 20 is cover plate, and 22 is micro- Type ultrasonic transducer, 23 is higher-order of oscillation electric signal transmission cable, and 24 is tension spring；This spring clamp structure in legend Being only the legend structure of signal, actual spring clamp structure is not limited to this legend spring clamp structure；Arrow in legend indicates should Micro-fluidic chip its when actual motion, driven by pressure at two ends difference, the flow direction of its sample liquid flow.

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 19 together and cover plate 20, and described substrate 19 and cover plate 20 are Plate object or tablet, that face towards this cover plate 20 of this substrate 19 is contained and is formed via mould pressing process or etching technics Channel structure, this substrate 19 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 19 being installed together bonded to each other is built into jointly with this cover plate 20 Containing the micro-fluidic chip of pipeline configuration and the liquid pool structure being attached thereto, described liquid pool is liquid pool the 1st, liquid pool the 2nd, liquid pool 10, the locations of structures of this pipeline is positioned at this substrate 19 interface zone bonded to each other with this cover plate 20, and its side of this window is by this Cover plate 20 blocks and opposite side is open, and the locations of structures of this window is exactly the structure position of described liquid pool the 1st, liquid pool the 2nd, 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 18 of piece, 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 when its The terminal 17 of liquid flowing in chip, this terminal 17 is located remotely from each other with this sample introduction end 18, and one end of this pipeline is via same position In this interface zone bonded to each other manifold shape turnout 3 respectively with this liquid pool 1 being positioned at sample introduction end 18 and this liquid pool 2 UNICOM, This remaining liquid pool i.e. liquid pool 10 UNICOM of the other end of this pipeline and the described terminal 17 being positioned at this micro-fluidic chip, with And, the working electrode being 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 being attached on this conductive electrode Becoming, the construction 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 this four working electrodes lays respectively in described four laterals, these four work Electrode is working electrode the 5th, working electrode the 6th, working electrode the 12nd, working electrode 13 respectively, and, this 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, This four kinds of antigenic substances are syphilis specific antigen TP0684, TP0453, TP0821 and TP0319 respectively, specifically launch to come Say, 5 be specific antigenic substance in its top layer gold size sensitive membrane structure being installed in lateral 4 be that syphilis specific resists 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 specific antigenic substance in its top layer gold size sensitive membrane structure is the working electrode of syphilis specific antigen TP0319, institute Stating working electrode the 5th, working electrode the 6th, working electrode the 12nd, its material of working electrode 13 is gold material or thermal decomposition conduction height Molecule material, described working electrode the 5th, working electrode the 6th, working electrode the 12nd, its pattern of working electrode 13 presents sheet or silk Shape, it is important that, this its material of substrate 19 is dimethyl silicone polymer material, and this its surface of substrate 19 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 elastic clip 15, two clamping limbs in opposite directions of this elastic clip 15 16th, the position of the neighbouring described terminal 17 at this micro-fluidic chip for 21 snap-in location, a described clamping limb at least in Upper attaching is fixing is equiped with miniature ultrasonic transducer units 22, and in legend, this miniature ultrasonic transducer units 22 is to attach fixing installing On one of which clamping limb 21, and, higher-order of oscillation electric signal transmission cable 23, this higher-order of oscillation electric signal transmission electricity One end of cable 23 links together with this miniature ultrasonic transducer units 22；This elastic clip 15 provides one and facilitates this device to tear open The function solving；This its major function of miniature ultrasonic transducer units 22 is when the actual sample introduction of micro-fluidic chip is tested, and utilizes its institute The ultrasonic wave launched reduces the interfacial tension between sample solution and the inwall of described pipeline so that it is can be compatible, and, profit By the distance difference between described sample introduction end 18 and described terminal 17 and this miniature ultrasonic transducer units 22 installation position and Difference on its ultrasonic intensity experienced, its interfacial tension of sample introduction end 18 described in induced synthesis and described terminal 17 its Difference between interfacial tension, interfacial tension difference meeting i.e. between sample introduction end 18 and terminal 17 for this two ends of this micro-fluidic chip I.e. form pressure gap between sample introduction end 18 and terminal 17 at this two ends of this micro-fluidic chip, this pressure gap can drive examination Sample solution flows to described terminal 17 direction；This its function of miniature ultrasonic transducer units 22 also include with its launched ultrasonic Ripple checks its absorption on described inner surface of pipeline of large biological molecule contained in sample, and then checks this polydimethylsiloxanes Its body of substrate 19 of alkane material is relative to the effect of swallowing up of this large biological molecule；The substrate 19 of described dimethyl silicone polymer material Its function include with cover plate 20 and working electrode the 5th, working electrode the 6th, working electrode the 12nd, working electrode 13 and to electrode 8 and Reference electrode 9 together builds this micro-fluidic chip, and softness simultaneously has its function of substrate of this elastic dimethyl silicone polymer material also Including with the character of its strong absorption to ultrasonic wave, ultrasonic wave is absorbed strongly, and thereby 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.

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 this elastic clip 15 and this miniature ultrasonic transducer units 22 set up on it and the higher-order of oscillation Electric signal transmission cable 23；Further, Fig. 1 and Fig. 2 is all depicted without described higher-order of oscillation electric signal generator and multiple tracks electricity The associate members such as chem workstation.

Involved elastic clip 15 is commercially available.Be available for this case structure use commercially available alternative spring clamp structure and moulding and Size etc., quality is various, and concrete elastic clip pattern can be selected as required.

Involved miniature ultrasonic transducer units 22 is commercially available；Also can customize to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal transmission cable 23 is commercially available；Also can be to ultrasonic transducer producer or cable special manufacturer Family's customization.

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

Each working electrode in this example structure and can be respectively via each 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 annex 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 on usual expression and significance refers to hydrophilic capillary glass tube；Capillary channel involved by this case is but hydrophobic The pipeline of capillary form.

Claims (10)

1. the controller used in syphilis diagnosis device that sample driving adapter can fast remove, 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 being formed via mould pressing process or etching technics is contained in that face towards this cover plate of this substrate Structure, this substrate possibly together be connected with this channel structure and pierce this substrate via mould pressing process, etching technics or simply punch 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 this substrate boundary 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 the terminal of its locations of structures of liquid pool 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 with this Liang Ge liquid pool UNICOM being positioned at sample introduction end, this of the other end of this pipeline and the described terminal being positioned at this micro-fluidic chip is remaining Under a liquid pool UNICOM, and, the working electrode being 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 construction 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 this four working electrodes lays respectively at described four laterals In, and, the specific antigen in its top layer gold size sensitive membrane structure of this four working electrodes is can be special to syphilis antibody respectively Property combine four kinds of Treponema pallidum antigen materials, this 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 sheet or thread, it is characterised in that its material of this substrate is dimethyl silicone polymer 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 elastic clip, two clamping limbs in opposite directions of this elastic clip The position of the neighbouring described terminal at this micro-fluidic chip for the snap-in location, a described clamping limb at least in attaches fixing It is equiped with miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, this higher-order of oscillation electric signal transmission cable One end links together with this miniature ultrasonic transducer units；This elastic clip provides a function facilitating this device to disassemble；This is micro- Its major function of type ultrasonic transducer is when the actual sample introduction of micro-fluidic chip is tested, and utilizes its ultrasonic wave launched to reduce 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 institute State on the distance difference between terminal and this miniature ultrasonic transducer units installation position and its ultrasonic intensity experienced Difference, the difference between its interfacial tension of sample introduction end and its interfacial tension of described terminal described in induced synthesis, this micro-fluidic chip should Interfacial tension difference between two ends can form pressure gap between this two ends of this micro-fluidic chip, and this pressure gap can drive Sample solution is to described end flow；Its function of this miniature ultrasonic transducer units also includes checking sample with the ultrasonic wave that it is launched In contained its absorption on described inner surface of pipeline of large biological molecule, and then check the base of this dimethyl silicone polymer material Its body of piece is relative to the effect of swallowing up of this large biological molecule；Its function of substrate of described dimethyl silicone polymer material include with cover plate and Working electrode and together build this micro-fluidic chip to electrode and reference electrode, soft this dimethyl silicone polymer material simultaneously having elasticity Its function of the substrate of matter also includes, with the character of its strong absorption to ultrasonic wave, strongly absorbing ultrasonic wave, and thereby at this This terminal of micro-fluidic chip is to the rapid decrement realizing ultrasonic intensity within the limited short distance between this sample introduction end.

2. the controller used in syphilis diagnosis device that a kind of sample driving adapter according to claim 1 can fast remove, its feature Being, described pipeline and described lateral and described manifold shape turnout are capillary channel.

3. the controller used in syphilis diagnosis device that a kind of sample driving adapter according to claim 1 can fast remove, its feature Being, described thermal decomposition conducting polymer is the conductive material being formed after anoxybiotic heat treatment by polyimides or polyacrylonitrile.

4. the controller used in syphilis diagnosis device that a kind of sample driving adapter according to claim 1 can fast remove, its feature Be, the width of described working electrode or diameter between 0.1 micron to 2000 microns, and, described working electrode Length is between 1 micron to 15000 microns.

5. the controller used in syphilis diagnosis device that a kind of sample driving adapter according to claim 1 can fast remove, its feature Being, the thickness of described gold size sensitive membrane is between 10 nanometers and 200 nanometers.

6. the controller used in syphilis diagnosis device that a kind of sample driving adapter according to claim 1 can fast remove, its feature Being, its material of described cover plate in structure is dimethyl silicone polymer material.

7. the controller used in syphilis diagnosis device that a kind of sample driving adapter according to claim 1 can fast remove, its feature Be, be positioned at this micro-fluidic chip this sample introduction end this 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.

8. the controller used in syphilis diagnosis device that a kind of sample driving adapter according to claim 1 can fast remove, its feature Being, the described cover plate in structure and its thickness of substrate are all between 1.0 millimeters and 5.0 millimeters.

9. the controller used in syphilis diagnosis device that a kind of sample driving adapter according to claim 1 can fast remove, 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.

10. the controller used in syphilis diagnosis device that a kind of sample driving adapter according to claim 1 can fast remove, its feature Being, its specified ultrasonic wave of this miniature ultrasonic transducer units transmitting power is between 5 milliwatts and 5000 milliwatts, and this is miniature super The frequency of its ultrasonic wave operationally launched of acoustic wave transducer is between 100KHz and 12MHz.