CN107262164A - Using PDMS as the co-detections of tumor markers in benign chip apparatus of the dual drive of substrate - Google Patents

Abstract

The present invention relates to a kind of co-detections of tumor markers in benign chip apparatus using PDMS as the dual drive of substrate, belong to analysis testing field.Dimethyl silicone polymer be PDMS its be used for making the substrate of the multichannel combined detection micro-fluidic chip of classifiable tumor mark, it is advantageous, also have problem；This case is directed to the problem.This case main points are, the selected PDMS with ecosystem surface of substrate, and fastening is positioned at the test liquid stream terminal of the micro-fluidic chip its neighbor positions manually by the hinge-type fixture for being attached to miniature ultrasonic transducer units, simultaneously, ultrasonic wave damper is installed at the sample introduction end of the micro-fluidic chip, reach ultrasonic intensity rapid decrement in short distance, so as to form interfacial tension difference at the two ends of the chip, difference offer is a kind of to drive the strength that test liquid stream flows along hydrophobic capillary channel to the terminal direction, the strength with Micropump its mechanicalness pumping strength for being included in structure while intercouple, Collaboration.

Description

Using PDMS as the co-detections of tumor markers in benign chip apparatus of the dual drive of substrate

Technical field

The present invention relates to a kind of co-detections of tumor markers in benign chip apparatus using PDMS as the dual drive of substrate, belong to analysis test Field.

Background technology

Tumor markers (tumor marker, TM) refers in the generation and breeding of tumour, is produced in itself by tumour cell Raw either reacted by body tumour cell and produce, reflection tumour exist and growth a class material, including protein, Hormone, enzyme (isodynamic enzyme) and oncoprotein etc..The tumor markers in blood samples of patients or body fluid is chemically examined, can be in cancer screening Early detection tumour, and observe the curative effect of oncotherapy and judge patient's prognosis.The tumor markers clinically commonly used at present has： (1) alpha-fetoprotein (AFP) is the mark of the tumours such as primary carcinoma of liver, carcinoma of testis, oophoroma；(2) carcinomebryonic antigen (CEA) is digestion The mark of the tumours such as system tumor, lung cancer, breast cancer；(3) CA125 (CA125) is the mark of the tumours such as oophoroma； (4) CA153 (CA153) is the mark of the tumours such as breast cancer；(5) CA19-9 (CA19-9) is digestive system tumor Mark；(6) CA724 (CA724) is the mark of the tumours such as stomach cancer, oophoroma；(7) carbohydrate antigen 242 (CA242) For the mark of digestive system tumor；(8) CA50 (CA50) is the mark of the tumours such as digestive system tumor, breast cancer, lung cancer Thing；(9) CYFRA21-1 (Cy211) is the mark of the tumours such as non-small cell lung cancer；(10) neuronspecific enolase (NSE) For the mark of the tumours such as ED-SCLC, neuroendocrine tumor；(11) PSA (PSA) is prostate cancer Tumor markers；(12) human chorionic gonadotrophin (HCG) is that embryonic cell carcinoma, trophoblastic tumor (suede cancer, vesicular mole) etc. are swollen The mark of knurl；(13) thyroglobulin (TG) is the mark of thyroid cancer；(14) ferritin (SF) is digestive system tumor, liver The mark of the tumours such as cancer, breast cancer, lung cancer；(15) B2M (β 2-MG) is in chronic lymphocytic leukemia, lymph Raised in the patient body fluids such as knurl, myeloma, lung cancer, thyroid cancer, nasopharyngeal carcinoma；(16) squamous cell antigen (SCC) be cervical carcinoma, The tumor markerses such as lung squamous cancer, the cancer of the esophagus.The tumor markers overwhelming majority clinically detected at present is not only present in malignant tumour In, exist in benign tumour, embryonic tissue, even in normal structure.Therefore, tumor markers has dynamic chek and multinomial Joint inspection is more valuable.So for numerous tumor markerses, clinically how to selectDifferent tumours understands some phases To special tumor markers, such as CA153 often appears in breast cancer；CEA often appears in intestinal cancer, stomach cancer；CA19-9 is often appeared in Intestinal cancer, cancer of pancreas；CA125 often appears in oophoroma etc..Clinician can be according to the different mark of different tumor examinations. Same tumour or different types of tumour can have one or more of tumor markerses abnormal；Same tumor markers can be in difference Tumour in occur.To improve the additive diagnostic value of tumor markers and determining which kind of mark can be supervised as the follow-up after treatment Index is surveyed, tumor markers joint-detection, the complementary tumor markers group of several sensitivity of reasonable selection, specific performance can be carried out Into best of breed, joint-detection is carried out.In general the joint-detection of tumor markers can improve the accuracy to diagnosing tumor.

Only with regard to Diagnostic Value of Several Serum Tumor Markers its joint-detection background of related itself general picture or overview for, may refer to Lower Chinese invention patent application case：CN200410041175.3、CN200510026780.8、CN200610040051.2、 CN200910064647.X。

Only for the microfluidic chip technology overall general picture of itself, famous micro-fluidic expert Mr. Lin Ping Cheng may refer to soon Before the monograph " diagram Microfluid based Lab on a chip " that goes out, the monograph is published via Science Press, and the monograph is for micro-fluidic Past of technology, now, and, in terms of vision of the future etc., suffer from detail, be deep into long discussion of detail.

So, the focal issue that this case that to have a talk below is paid special attention to.

The basic framework of micro-fluidic chip, including it is etched with the substrate of small fluid course and the cover plate fit together therewith, Small fluid course on the substrate, assembling upper cover plate before, it is apparent on see to be exactly some micro-channels, wait until thereon After covering cover plate, just real closure forms the small fluid course, and the conduit inner surface of the 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 is completed 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 the micro-channel The state or property on surface substantially determine the integrality or property of the small fluid course；Therefore say, this is built in base The inner surface state or inner surface property of micro-channel on piece are key factors；In principle, it is any to keep or protecting substantially The material of its solid forms is held, can be used to make substrate and cover plate, such as, the material that can act as substrate and cover plate can be with It is monocrystalline silicon piece, quartz plate, sheet glass, high polymer such as dimethyl silicone polymer, polymethyl methacrylate, makrolon etc. Deng；Certainly, the selection of substrate and the selection of cover plate be able to can also be differed with identical；From material consumption, manufacture difficulty and From the point of view of in terms of application popularization prospect etc., between these materials exist not small difference, the especially selection of that substrate, influence compared with Greatly.

In various substrate making materials, dimethyl silicone polymer, i.e. PDMS, comparatively very easily shaping, so Substrate on make that micro-channel is extremely simple, and the lower cost for material makes substrate with the polydimethyl siloxane material, Micro-channel is being suppressed or etched thereon, and is being engaged with the cover plate that the cheap material such as glass or polypropylene or other plastic sheets makes, 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, promotes.

But, thing is really not so simple.

First, this polydimethyl siloxane material, that is, the material that the letter PDMS that abridges is referred to, itself are a kind of strong Hydrophobic material, micro-channel is built on this material, if without being operated for the modified of the micro-channel surface, then, After overall assembling is completed, that is, cover after cover plate, because the micro-channel its inner surface in structure occupies most liquid circulation The inner surface in road, then, its strong hydrophobic property of the PDMS micro-channels inner surface, is deciding factor, it can cause class Be similar to the aqueous solution the fine liquid stream of polar liquid by becoming very difficult, its flow resistance is big, or even general Micropump is all It is difficult to promote, certainly, if cover plate also selects to use the PDMS material, then, problem is substantially identical, similar； Therefore, among prior art, modification is modified particular for the micro-channel inner surface on the PDMS material, is necessary Operation；So, this is pretty troublesome for the modified operation of PDMS micro-channel inner surfacesThat falls nor this problem, structure Perplex into serious technical, be another problem：PDMS polymer molecules tool inside its body phase of this PDMS material substrate There are PDMS polymer molecules inside the characteristic for diffusing to the surface, migrating automatically, this substrate body phase to diffuse to the surface, move automatically The characteristic of shifting, will cause the state after modification by its inner surface of that micro-channel of surface modifying and decorating can not maintain foot Enough long time, the holding time for micro-channel its inner surface state after that is surface-modified is substantially only sufficient to complete in laboratory The time of portion's test experiments needs；In other words, by surface modification or the PDMS micro-channel inner surfaces of surface modification, its The surface state that is formed can not be lasting after modification or after saying modification, but soon automatically tend to or say and become surface again and change Surface state before property, returns to the strong hydrophobic surface state of that script in the shorter time, then, just think, Such micro-fluidic chip can largely make, mass storage, be widely popularized, and answer is it is obvious that is, impossible. Micro-channel on this PDMS material, can not pump similar to the fine liquid stream of polar solvent of the aqueous solution if not doing surface modification Send and pass through, chip also cannot just be used；And if having done surface modification, the state after its modification can not be persistently kept again, also Being equally can not popularization and application.

So, how to accomplish that substrate can either be made using cheap PDMS material, and table in the micro-channel can be released Face decorating state can not persistently, chip can not largely make, largely lay in so that be widely popularized it is such a make this area it is numerous specially The puzzlement that industry personnel are entangled with for a long time, the highly difficult problem that exactly one its obvious technology barrier can not despise.

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

Second, the PDMS material of non-surface modification, above it is stated that, its surface is strongly hydrophobic, this strong hydrophobic Material surface and also another problem, that is, this strong hydrophobic PDMS surfaces can adsorb large biological molecule, and And, these adsorbed large biological molecules can also further depression further on PDMS surfaces, gradually fall into gradually deep, directly It is trapped in heavy within the body phase of PDMS substrates, in fact, this process is partly also due to inside PDMS material body phase Polymer molecule, which has, to be diffused to the surface, caused by travel motion；Such case, can also be explained from another angle, i.e. Continuously from inside PDMS body phases to its diffusion into the surface, migration those polymer molecules, its result moved, be by Gradually those are involved within the body phase of PDMS substrates by the large biological molecule of adsorption, briefly, these are inhaled Attached large biological molecule is exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up large biological molecule Phenomenon, the influence caused by it necessarily causes the severe deviations of all kinds of test data of experiment for being related to large biological molecule.

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

On PDMS substrates in related experiment test process its body phase constantly swallow up test associated biomolecule macromolecular phenomenon, separately It is to say that one kind, which is explained, there are substantial amounts of Minute pores in PDMS body phases, and associated biomolecule macromolecular is by after adsorption, depression Into these Minute pores, and then swallowed up；However, inventor thinks, those can allow the air point of miniature scale Son squeezes into the Minute pores therebetween, and being not equal to them also can directly allow that the large biological molecule of relative large scale enters, and two Person's difference on yardstick is huge, must not make sweeping generalizations.Explanation is bypassed, in any case, the biology of object is analyzed as dependence test Macromolecular is adsorbed by PDMS substrate micro-channels inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is known objective The phenomenon of presence.

, can be from containment PDMS surfaces to life in order to prevent this PDMS substrate bodies relative to the effect of swallowing up of large biological molecule The absorption of thing macromolecular is addressed, and method is chemically modified modification aiming at the PDMS material surface, for For PDMS is the situation of substrate material, modification exactly is chemically modified to the surface of described micro-channel part, by changing The micro-channel inner surface of modification is learned, its absorption to large biological molecule can be contained, and then avoid large biological molecule quilt PDMS substrate body phases are swallowed up；But, or that old problem, that is, the chemical modification on PDMS material surface changes Surface state after property can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface automatically, The process of migration, soon can become that micro-channel inner surface state being modified by surface chemical modification again script strong and dredge Water and the state of strong adsorption large biological molecule, in other words, no matter how professionals in the field turn from side to side, the PDMS 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 absorption process of the PDMS substrate micro-channel inner surfaces to large biological molecule, and then prevents PDMS substrate body phases The effect of swallowing up to large biological molecule so that related chip manufactured goods are able to maintain that a prolonged enough, rational shelf-life, It is exactly a very intractable problem.The problem makes the numerous specialties in this area as another problem addressed above, equally Personnel are entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise.The hardly possible Also be present many year in topic, so far, also not yet properly settled.

Third, as described above, the PDMS micro-channel inner surfaces are strongly hydrophobic, and targetedly surface chemical modification or come to the surface Learn modification to be difficult to again persistently, therefore, actually can only still belong to effective short in the surface state after the modification of its surface or surface modification It is used within phase；If have passed through that ofer short duration period of validity, and still by force if use, due to surface shape State already again close to hydrophobic state, is then certainly existed than larger flow resistance using usual Micropump driving test liquid stream, So, just test liquid can only be forced to flow to target direction flowing by increasing Micropump pump power and pumping pressure, as described above, This PDMS material is soft, pumps test liquid stream with too high, machinery pumping pressure, causing the substrate, it enters Bubbling, expanded, distortion, deformation, also, this high-pressure situations occur for the micro-channel that sample end includes sample introduction end near zone Under, also easily occur the stripping between substrate and cover plate, this feelings in the sample introduction end and its micro-channel of near zone and its periphery Under shape, sample solution flows in the crack of the appearance between the substrate and cover plate that are formed after the entrance stripping everywhere, this reality Border causes the damage of the micro-fluidic chip；Certainly, it is not in place if surface modification or surface modification script, also result in There is said circumstances within the of short duration usual term of validity；It is above-mentioned in the case where carrying out liquid stream driving using additional Micropump merely The problem exists all the time.If be modified or the pre action such as surface modification as described above, not doing any surface completely, So, the above-mentioned problem will be even more serious, even without occur micro-channel bubbling described in sample introduction end and its near zone, it is expanded, Between distortion, deformation and substrate and cover plate the problems such as peel off, merely because the flow resistance is excessive, using high pressure Micropump also not Test liquid stream must can be driven to be marched forward towards terminal side.

The content of the invention

The technical problems to be solved by the invention are to provide a package solution, while solving three addressed above The a series of problem actually mutually involved together of aspect, also, the solution is a kind of new applied to building Can be for six kinds than more typical primary tumor mark progress examination simultaneously, while the micro flow control chip device of detection.

The present invention solves the technical problem by following scheme, and the device that the program is provided is a kind of double by substrate of PDMS The co-detections of tumor markers in benign chip apparatus of driving, the program is characterized in that the structure of the device includes micro-fluidic chip, and this is micro- The structure of fluidic chip includes the substrate and cover plate of installing bonded to each other together, and the substrate and cover plate are plate object or sheet The channel structure via mould pressing process or etching technics formation is contained in thing, that face towards the cover plate of the substrate, bonded to each other The substrate being installed together has been built into the micro-fluidic chip containing pipeline configuration, the locations of structures of the pipeline jointly with the cover plate Positioned at the substrate and cover plate juncture area bonded to each other, the two ends of the pipeline respectively with the sample introduction end of the micro-fluidic chip and Terminal is connected, and the sample introduction end is the injection end of the micro-fluidic chip sample solution, and the terminal is that the actual sample introduction of the micro-fluidic chip is surveyed The terminal that sample solution flows in its chip during examination, the terminal is located remotely from each other with the sample introduction end, between the terminal and the sample introduction end Distance between 3 centimetres and 10 centimetres, in the pipeline on diverse location in order or backward be equiped with working electrode and To electrode and reference electrode, the order refers to its locations of structures of the reference electrode closer to the terminal location, described Backward refers to the reference electrode locations of structures closer to the sample introduction end position, the working electrode by conductive electrode and The gold size sensitive membrane for having embedded tumor markers antibody being attached on the conductive electrode is constituted, and the construction of the pipeline is presented in parallel Construction, the pipeline in parallel construction is made up of six lateral parallel connections, and the pipeline of the presentation parallel construction is outside it Shape profile is similar to the profile of parallel circuit, and the quantity of the working electrode is six, the installation position point of six working electrodes Not Wei Yu in six laterals, and, the tumor markers in the sensitive membrane structure of its top layer gold size of six working electrodes Antibody is the six kinds of tumor markers antibody materials that can be specifically bound to tumor markers antigen, six kinds of antibody materials point respectively It is not tumor markers antibody A FP, CEA, PSA, CA125, CA19-9 and CA15-3, the antigen is the antigen of broad sense, The antibody is the antibody of broad sense, and its material of the working electrode is argent material, gold material, carbon material or thermal decomposition Column, sheet or thread is presented in conducting polymer material, its pattern of the working electrode, and its material of the substrate is poly dimethyl silicon Oxygen alkane material, its surface of the substrate is the surface of primary form, the surface of the primary form its be intended to refer to not by any The surface of the primary form of surface chemical modification or the material of any surface chemical modification, the structure of the device also includes hinge-type Fixture, the hinge-type fixture its appearance profile likeness in form hinge, the hinge-type fixture by two hinges being mutually hinged and Match and connected together with the fastening screw with the fastening screw through a fastening screw of two hinges and one Nut for fastening and hand break loose manually is constituted, and two hinges of the hinge-type fixture are respectively mutually drawn close and clamped with its tip The micro-fluidic chip, the tip is positioned in the locations of structures of the neighbouring terminal of the micro-fluidic chip, at least in Fixation is attached in one hinge and is equiped with miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, the height Frequency vibration swings one end of electric signal transmission cable and the miniature ultrasonic transducer units link together；The hinge-type fixture provides one The function of facilitating the device to disassemble；Its major function of the miniature ultrasonic transducer units be in the test of micro-fluidic chip actual sample introduction, The ultrasonic wave launched using it reduces the interfacial tension between sample solution and the inwall of its inner passage of micro-fluidic chip, Can be compatible, also, using between the sample introduction end and the terminal and the miniature ultrasonic transducer units installation position Difference in distance difference and its ultrasonic intensity experienced, its interfacial tension of sample introduction end described in induced synthesis and the end The difference between its interfacial tension is held, what the interfacial tension difference between the micro-fluidic chip two ends can be in the micro-fluidic chip should Pressure gap is formed between two ends, the pressure gap can drive sample solution to the end flow；The miniature ultrasonic transducer units Its function also include with its ultrasonic wave launched check in sample contained large biological molecule its in the micro-fluidic chip in it Absorption on portion's channel inner surface, and then check the substrate of the dimethyl silicone polymer material its body phase the large biological molecule is gulped down Do not act on；It is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and include with it to the strong absorption of ultrasonic wave Property, is absorbed strongly to ultrasonic wave, and thereby in micro-fluidic chip terminal to the limited short distance between the sample introduction end The rapid decrement of ultrasonic intensity is realized within；And, Micropump, the Micropump is connected with the sample introduction end；The function of the Micropump is, Interfacial tension between the inwall of the sample solution with its inner passage of micro-fluidic chip is reduced by the ul-trasonic irradiation, phase Between under the increased precondition of compatibility, come with the mechanicalness pumping strength of the Micropump between the two ends that are induced the ultrasonic wave Interfacial tension difference its driving force brought support mutually, adjust mutually, be mutually coupled, converged in the way of Collaboration It is polymerized to the strength that one driving test liquid flows to the terminal direction flowing；Described its thickness of cover plate and substrate is between 1.0 millimeters Between 5.0 millimeters；And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；This surpasses Its material of sound wave damper is microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force is accompanied Two clamping limbs, the medial surface of each clamping limb is relative with the medial surface of another clamping limb, the medial surface of one of clamping limb Be close to the sample introduction end of the micro-fluidic chip, the medial surface of another clamping limb is close to the ultrasonic wave damper, the elastic clip with Its gripping strength by the sample introduction end of the micro-fluidic chip and the ultrasonic wave damper it is bonded to each other clip together, the ultrasonic wave abatement The strong consumption to ultrasonic wave that device is brought with its material, is further supported in micro-fluidic chip terminal to the sample introduction The rapid decrement of ultrasonic intensity is realized within limited short distance between end, and thereby further expands described its boundary of sample introduction end Difference between face tension force and the terminal its interfacial tension.

The tumor markers antibody is the antibody of broad sense, and the antibody of the broad sense refers to possessing antibody function or functionally similar Can occur to combine and formed immune complex or immune compound with the various involved tumor markerses of corresponding clinic in antibody The material of the analog of thing；The tumor markers antigen is the antigen of broad sense, and the antigen of the broad sense is referred to can be using accordingly Antibody or be functionally similar to antibody material carry out enzyme mark detection it is various it is clinical involved the need for differentiate, the tumor-marker of detection Thing.

Described miniature ultrasonic transducer units can certainly be all installed in two hinges；But, only installing one is micro- Type ultrasonic transducer is dealt with enough to be used.

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

The word of Micropump one art-recognized meanings of itself are known for the professional in micro-fluidic chip field.

The Micropump both can be the Micropump of external form；The Micropump can also be done into or say inside the embedded micro-fluidic chip The Micropump of the built in version of its sample introduction end structure position or the sample introduction end Near-neighbor Structure position.

The Micropump such as miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.

The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and tumor markers antibody-solutions uniformly, uses point sample instrument Point sample is coated on specified structure position, and forms its drying and forming-film.Tumor markers antibody in the gold size sensitive membrane is equal The tumor markers antibody marked for horseradish peroxidase or glucose oxidase, the gold size sensitive membrane has been included as fixing Above-mentioned each tumor markers antibody and introduce complementary medium therein, the complementary medium for example chitosan, cellulose acetate, Gelatin is therein a kind of or their mixture.

The pipeline in the microfluidic chip structure includes the lateral, and its internal diameter size may each be arbitrarily selected Size, still, for less with the consideration in terms of prepare liquid sample and reduction reagent loss, the pipeline includes described as far as possible The passage of the preferred capillary level of lateral, the passage of the capillary level implies that the interior of its internal diameter and the capillary on ordinary meaning The suitable passage in footpath.The shape of cross section of its inner passage of capillary can be arbitrary shape, the shape of cross section example Such as circular, oval, square, rectangle, bar shaped, naturally it is also possible to be arbitrarily the presence of the linear of bending, also, the hair The interior shape of tubule is with the extension of pipeline, and the shape of cross section of different parts can also allow to be different shapes.Only with regard to hair For the word of tubule one, its art-recognized meanings is known.

What is be related in structure is the electrode of microsize to electrode and reference electrode, and its electrode shape may each be any choosing Fixed shape, the arbitrarily selected shape such as column, sheet, strip or thread etc..It is described to electrode and the ginseng Art-recognized meanings than the electrode vocabulary of itself are known.

It is public only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field Know.

Various sizes, variously-shaped ultrasonic transducer are commercially available；Commercially available miniature ultrasonic transducer units its sizes can be with It is small to the magnitude only calculated with millimeter.

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

Only with regard to naked PDMS substrates itself micro-channel molding or lithographic technique for, be open-and-shut known technology.

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

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

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

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

This case device can further include some annexes, the annex such as multiple tracks electrochemical workstation etc., institute certainly The art-recognized meanings for stating multiple tracks electrochemical workstation are known.Each working electrode for being related in this case microfluidic chip structure and , can be respectively via corresponding special the corresponding interface got lines crossed with the multiple tracks electrochemical workstation to electrode and reference electrode etc. Coupled.It is described that special to get lines crossed be for each the corresponding interface of each electrode and the multiple tracks electrochemical workstation is carried out into phase The private cable being mutually coupled with.The micro-fluidic chip in this case device, its structure can also include micro-valve, the number of the micro-valve Amount is not limited, according to actual needs, and the micro-valve can be installed in any required position installed in the microfluidic chip structure； The word of micro-valve one is for the professional of micro fluidic chip technical field, and the art-recognized meanings of itself are known；The micro-valve The manufacturing technology of itself and the use of technology is also known；The component that the micro-valve is not required.

The diameter of the working electrode can allow to be that any setting is easily installed the suitable diameter used, it is however recommended to Or say preferred its scope of the diameter between 0.1 micron to 2000 microns；The length of the working electrode can permit Permitted to be that any setting is easily installed the length used, it is however recommended to or to say preferred its scope of the length be at 1 micron To between 15000 microns.

The gold size for being installed in the working electrode surface layer by spraying or point sample instrument point sample or the coating of other appropriate process is quick Feel film, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness, still, push away Preferred thickness is between 10 nanometers and 200 nanometers in other words for the thickness recommended.

The 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 Realized into the micro-fluidic chip of only 2.0 centimetres to 3.0 centimetres of super-small of length, and in the extremely short distance to ultrasonic wave Extremely fast decay, can preferably dimethyl silicone polymer be used as cover plate.Certainly, selected on large-sized micro-fluidic chip It is used as the cover plate using dimethyl silicone polymer, is also that this case technical scheme is allowed.

Described its thickness of cover plate and substrate can allow be any setting be easy to assembling thickness, the thickness of recommendation or say preferably Thickness be between 1.0 millimeters and 5.0 millimeters.Less thickness is conducive to saving material.

Described its size of ultrasonic wave damper is not limited, and described its length of ultrasonic wave damper, width, thickness may each be according to need The arbitrary size to be set.

It is known in field of rubber technology only for the word of microcellular rubber one art-recognized meanings of itself.

The microcellular rubber is commercially available.

It is known in field of rubber technology only for the word of sponge rubber one art-recognized meanings of itself.

The sponge rubber is commercially available.

It is known in technical field of macromolecules only for the word of microporous polyurethane elastomer one art-recognized meanings of itself.

The polyurethane micropore elastomer material is commercially available.

The microcellular rubber preferred microporous silicon rubber or micropore fluorubber.

It is known in field of rubber technology only for the word of micropore silicon rubber one art-recognized meanings of itself.

The microporous silicon Rubber market is on sale.

It is known in field of rubber technology only for the word of micropore fluorubber one art-recognized meanings of itself.

The micropore fluorubber is commercially available.

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

The elastic clip is commercially available.

The application method of this case micro-fluidic chip：

This case is flowed with dual drive coupling operating mode driving liquid stream in the capillary channel of the six-channel microfluidic chip, Joint-detection is carried out to six kinds of classifiable tumor mark antigens respectively using multi-channel electrochemical analyzer device.

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

1st, blood serum sample liquid is added in micro-pipe road, under dual drive coupling operating mode driving, various tumor markerses The tumor-marker for the corresponding horseradish peroxidase-labeled that antigen molecule is embedded by gold size sensitive membrane on electrode surface in each passage Thing antibody capture.

2nd, the tumor markers antigen in the tumor markers antibody and blood serum sample of horseradish peroxidase-labeled forms immune multiple Compound.

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

4th, result is subjected to comprehensive analysis, comprehensive diagnos is carried out to tumor markers antigen.

It is an advantage of the invention that its close position positions the hinge-type fixture in the terminal of the micro-fluidic chip, with The miniature ultrasonic transducer units installed, the low-power launched using it, high-frequency band are attached in its hinge of the hinge-type fixture Ultrasonic wave so that without surface chemical modification or surface chemical modification strong hydrophobic micro-fluidic chip internal pipeline its Compatibility between tube wall and the test object aqueous solution is significantly increased, and this passes through possible there is provided a reality for test liquid stream Property；Meanwhile, using its strong absorbability to ultrasonic wave of dimethyl silicone polymer substrate, in shorter distance, also Be, from the terminal to the very short distance of only several centimeters yardsticks the sample introduction end in, reach the quick of ultrasonic intensity Successively decrease, interfacial tension between the difference of the interfacial tension, the two ends is thereby caused at the two ends of the micro-fluidic chip Difference can cause a kind of driving force, this kind because caused by interfacial tension difference its function of driving force be to drive test liquid stream to exist Originally flowed in strong hydrophobic capillary channel to the terminal direction；And the simultaneous Micropump in structure, its function It is that the interfacial tension between the inwall of the sample solution and its inner passage of micro-fluidic chip is dropped by the ul-trasonic irradiation Under low, the alternate increased precondition of compatibility, described two induced with the ultrasonic wave are come with the mechanicalness pumping strength of the Micropump Interfacial tension difference its driving force brought between end is supported mutually, adjusts mutually, is mutually coupled, with Collaboration Mode pools the strength that one driving test liquid flows to the terminal direction flowing；The presence of the Micropump so that the miniature ultrasonic Its ultrasonic wave emissive porwer of wave transducer can be allowed to appropriate reduction, and this in detection object for containing ultrasonic wave sensitive composition Situation is particularly suitable for；And by the presence of the ultrasonic transducer and its radiated ultrasonic wave, it is possible to increase alternate compatibility, drop Low interfacial tension, and the two ends interfacial tension difference special driving force that it is brought is provided, then, in this case, Its flow resistance in the micro-channel of test liquid stream is greatly reduced, and correspondingly, its running resistance of the Micropump is greatly reduced, so, The Micropump just can be to carry out the pumping work for the sample solution than relatively low pumping pressure, due to mechanical pumping Pressure is greatly reduced, therefore, in such a situation, be just not susceptible to because sample introduction terminal tool pumping pressure it is excessive caused by Between the micro-channel bubbling of the sample introduction end and its near zone, expansion, deformation, distortion and the region substrate and cover plate The problems such as stripping etc.；This case dual drive couples the scheme of running and adds the manipulation acted for the sample fluid flow Property, it can allow for coming using the multiple indexs of ultrasonic intensity, ultrasonic frequency, Micropump pump power, Micropump pumping pressure etc. Flow rate, flowing action for the flowing include flow forward or suspend flowing or accelerate flowing etc. flowing action progress many Parameter is accurately manipulated；By the scheme of this case dual drive coupling running, entirely without must be to the base of the dimethyl silicone polymer material Any surface chemical modification of its micro-channel of piece etc. relevant surfaces progress or surface chemical modification, have altogether dispensed with the surface chemistry Modification or the laborious procedures of surface chemical modification；On the other hand, the ultrasonic wave of the low-power, high-frequency band, additionally it is possible to containment examination The absorption of large biological molecule in sample on literalness naked its inner surface of pipeline of dimethyl silicone polymer substrate, and then contain The swallow up effect of its body phase of dimethyl silicone polymer substrate to the large biological molecule；The antigen, antibody and antigen are with resisting The Reversible binding thing of body is all the type for belonging to described large biological molecule certainly；Due to described suction-operated and described gulp down Do not act on and effectively being contained, therefore, dependence test result will be better able to objectively reflect actual conditions；The low-power, height The effect of frequent section ultrasonic wave, also include facilitating the Reversible binding between antigen, antibody react certainly quickly reaches, and this causes Dependence test operation can be with than the completion of faster speed.

As described above, the presence of the Micropump so that its ultrasonic wave emissive porwer of the miniature ultrasonic transducer units can be allowed to fit Degree reduction, then, the feature helps to protect its sensitive coating of the working electrode, is allowed to from ultrasound injury.

Based on this case scheme, repaiied completely without the surface chemistry carried out for the dimethyl silicone polymer substrate its relevant surfaces Decorations or surface chemical modification operation, therefore, this surface chemical modification layer or surface chemical modification layer not need to exist, So, its body phase interior polymer molecule of the dimethyl silicone polymer substrate is constantly diffused to the surface, migrated caused by it automatically Damaging influence to surface chemical modification layer or surface chemical modification layer is also just not present.

The technical scheme of this case has dissolved its application related one to dimethyl silicone polymer substrate addressed above totally Row technical barrier.Based on this case scheme, the polydimethyl siloxane material of this kind very cheap and easily processing and fabricating just has can Can in the micro-fluidic chip its prepare, production, using etc. field play bigger effect.

The miniature ultrasonic transducer units have been installed in fixation in the hinge-type fixture its hinge in this case structure, and the structure is provided One facilitates the function that the device is disassembled, in this way, the hinge-type fixture is together with appended miniature ultrasonic transducer units in its hinge Just easily it can be mutually disengaged with the micro-fluidic chip, then, the component that the part can freely depart from just can circulate benignly ground Reuse many times；The architectural feature is conducive to saving the use cost of the device.

This case its installation position is located at the ultrasonic wave damper at the sample introduction end, from its terminal of this case micro-fluidic chip to entering Said on the sport technique segment that ultrasonic intensity rapid decrement is realized in the such short distance in sample end, the ultrasonic wave damper its function as The size expansion device of micro-fluidic chip, in other words, the ultrasonic wave damper its function as significantly extend it is micro-fluidic Its terminal of chip the distance between to sample introduction end, be the equal of from length of several centimetres of the extension of script to more than ten centimetres or Twenties centimetres of length or longer length, so so that described terminal is strong to the ultrasonic wave between sample introduction end in short distance The sport technique segment of degree rapid decrement can relatively easily be reached, also, the size expansion device namely the ultrasonic wave damper its Installation and removal are all very convenient, it is important that it can also be reused.

Its presence of the ultrasonic wave damper in this case device, further reduce to its pumping pressure of Micropump and pump power according to Rely；Correspondingly, its running resistance of the Micropump is further greatly reduced, so, and the Micropump just can be with lower pumping Pressure carries out the pumping work for the sample solution, because mechanical pumping pressure is further greatly reduced, Therefore, in such a situation, just be less susceptible to occur because sample introduction terminal tool pumping pressure it is excessive caused by the sample introduction end and The problems such as stripping between the micro-channel bubbling of its near zone, expansion, deformation, distortion and the region substrate and cover plate etc.； The scheme of this case dual drive coupling running is further added for the test liquid due to its presence of the ultrasonic wave damper The handling of flowing action is flowed, wherein, the factor that can adjust includes ultrasonic intensity, ultrasonic frequency, Micropump pump power, micro- Pump pumps pressure, and, the selection and use of ultrasonic wave damper material, the selection of ultrasonic wave damper block size and use, The selection of the size of its corresponding ultrasonic wave abatement ability of ultrasonic wave damper and use etc., this kind of many adjustable factor it is same When exist, can more operation indexs, further, more it is multifactor adjustably for the flowing flow rate, stream Action includes flow forward or pause flowing or accelerates flowing etc. flowing action to carry out the accurate manipulation under more parameters.

The framework of its large-scale integrated of this case micro-fluidic chip, determines it among actual test application, to Serum samples The need for measure smaller, this helps to reduce the body and mind damage of related subject.

Brief description of the drawings

Fig. 1 is its rough outside side view of this case micro flow control chip device.

In figure, 1 is hinge-type fixture, and 2 indicate linkwork positions, and 3 be fastening screw, and 4 be higher-order of oscillation telecommunication Number transmission cable, 5 be miniature ultrasonic transducer units, and 6,11 be two different hinges of locations of structures respectively, and 7 be cover plate, 8 It is substrate, 9 be sample introduction end, and 10 be terminal, and 12 be nut, and 13 be infusion tube, and 14 be Micropump；The conjunction in legend Page clamp structure is only the legend structure of signal, and actual its structure of the hinge-type fixture is not limited to the legend hinge-type fixture knot Structure；Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, its test liquid stream Flow direction.The ultrasonic wave damper is depicted without in legend；Also the elastic clip is depicted without in legend.

Embodiment

In this case that Fig. 1 is shown embodiment, its main points of the example are that the structure of the device includes micro-fluidic chip, should The structure of micro-fluidic chip includes the substrate 8 and cover plate 7 of installing bonded to each other together, and the substrate 8 and cover plate 7 are plate Contain the conduit via mould pressing process or etching technics formation in shape thing or tablet, that face towards the cover plate 7 of the substrate 8 Structure, substrate 8 bonded to each other being installed together has been built into the micro-fluidic chip containing pipeline configuration jointly with the cover plate 7, The locations of structures of the pipeline is located at the substrate 8 and the cover plate 7 juncture area bonded to each other, and the two ends of the pipeline are micro- with this respectively The sample introduction end 9 of fluidic chip and terminal 10 are connected, and the sample introduction end 9 is the injection end of the micro-fluidic chip sample solution, should Terminal 10 is the terminal of sample solution flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, the terminal 10 and the sample introduction End 9 is located remotely from each other, and the distance between the terminal 10 and the sample introduction end 9 are between 3 centimetres and 10 centimetres, in the pipeline On diverse location in order or backward is equiped with working electrode and to electrode and reference electrode, the order refers to the ginseng Than its locations of structures of electrode closer to the position of terminal 10, the backward refer to the reference electrode locations of structures closer to The position of sample introduction end 9, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded tumour mark The gold size sensitive membrane of will thing antibody is constituted, and parallel construction is presented in the construction of the pipeline, and the pipeline in parallel construction is by six points Branch pipe(tube) parallel connection is constituted, and its appearance profile of the pipeline of the presentation parallel construction is similar to the profile of parallel circuit, the work The quantity for making electrode is six, and the installation position of six working electrodes is located in six laterals respectively, and, should Tumor markers antibody in six sensitive membrane structures of its top layer gold size of working electrode is respectively can be special to tumor markers antigen Property combine six kinds of tumor markers antibody materials, six kinds of antibody materials be respectively tumor markers antibody A FP, CEA, PSA, CA125, CA19-9 and CA15-3, the antigen are the antigen of broad sense, and the antibody is the antibody of broad sense, the working electrode Its material is argent material, gold material, carbon material or thermal decomposition conducting polymer material, its pattern of the working electrode Column, sheet or thread is presented, its material of the substrate 8 is dimethyl silicone polymer material, and its surface of substrate 8 is primary shape The surface of state, the surface of the primary form its be intended to refer to not pass through any surface chemical modification or any surface chemical modification The material primary form surface, the structure of the device also includes hinge-type fixture 1, its profile wheel of the hinge-type fixture 1 Profile like hinge, the hinge-type fixture 1 by two hinges 6,11 for being mutually hinged and through two hinges 6, 11 fastening screw 3 and one matched with the fastening screw 3 and with the fastening screw 3 connects together is used for hand The nut 12 of dynamic fastening and hand break loose is constituted, and the nut 12 is employed in this example is easier manually operated butterfly spiral shell Cap, butterfly nut is commercially available, and two hinges 6,11 of the hinge-type fixture 1 are respectively mutually drawn close with its tip and clamp this Micro-fluidic chip, the tip is positioned in the locations of structures of the neighbouring terminal 10 of the micro-fluidic chip, at least in A hinge on attach fixation be equiped with miniature ultrasonic transducer units, this example, the miniature ultrasonic transducer units 5 be patch It is attached to be fixed in hinge 6, and, higher-order of oscillation electric signal transmission cable 4, the one of the higher-order of oscillation electric signal transmission cable 4 End links together with the miniature ultrasonic transducer units 5；The hinge-type fixture 1 facilitates the function that the device is disassembled there is provided one； Its major function of the miniature ultrasonic transducer units 5 is the ultrasonic wave launched using it in the actual sample introduction test of micro-fluidic chip , can be compatible to reduce the interfacial tension between sample solution and the inwall of its inner passage of micro-fluidic chip, also, Using the distance between the sample introduction end 9 and the terminal 10 and the installation position of miniature ultrasonic transducer units 5 difference and Difference on its ultrasonic intensity experienced, its interfacial tension of sample introduction end 9 described in induced synthesis and described its boundary of terminal 10 Interfacial tension difference between difference between the tension force of face, the micro-fluidic chip two ends 9,10 being somebody's turn to do in the micro-fluidic chip Pressure gap is formed between two ends 9,10, the pressure gap can drive sample solution to be flowed to the direction of terminal 10；This is micro- Type ultrasonic transducer 5 its function also include with its ultrasonic wave launched check large biological molecule contained in sample its Absorption on its inner passage inner surface of the micro-fluidic chip, and then check the substrate 8 of the dimethyl silicone polymer material its body phase The effect of swallowing up to the large biological molecule；It is soft and have the substrate 8 of the dimethyl silicone polymer material of elasticity its function include with Its property to the strong absorption of ultrasonic wave, is absorbed strongly to ultrasonic wave, and thereby in the micro-fluidic chip, the terminal 10 is arrived The rapid decrement of ultrasonic intensity is realized within limited short distance between the sample introduction end 9；And, Micropump 14, the Micropump 14 are connected with the sample introduction end 9；The function of the Micropump 14 is, in the sample solution and its inner passage of the micro-fluidic chip Interfacial tension between wall is reduced by the ul-trasonic irradiation, under the increased precondition of alternate compatibility, with the Micropump 14 Its driving force for being brought of interfacial tension difference between the two ends 9,10 that are induced come the ultrasonic wave of mechanicalness pumping strength Amount is supported mutually, adjusts mutually, is mutually coupled, and one driving test liquid is pooled in the way of Collaboration and flows to the terminal The strength of 10 directions flowing；Its thickness of the cover plate 7 and substrate 8 is between 1.0 millimeters and 5.0 millimeters；And, Ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；Its material of the ultrasonic wave damper is micropore Rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, each clamping limb Medial surface it is relative with the medial surface of another clamping limb, the medial surface of one of clamping limb is close to entering for the micro-fluidic chip Sample end 9, the medial surface of another clamping limb is close to the ultrasonic wave damper, and the elastic clip is micro-fluidic by this with its gripping strength The sample introduction end 9 of chip and the ultrasonic wave damper are clipped together bonded to each otherly, what the ultrasonic wave damper was brought with its material Strong consumption to ultrasonic wave, is further supported limited between micro-fluidic chip terminal 10 to the sample introduction end 9 Short distance within realize the rapid decrement of ultrasonic intensity, and thereby further expand described its interfacial tension of sample introduction end 9 and institute State the difference between terminal 10 its interfacial tension.

The ultrasonic wave damper is depicted without in legend；Also the elastic clip is depicted without in legend.

Arrow in legend indicate the micro-fluidic chip its in actual motion, by two ends 9,10 pressure differentials drive, its The flow direction of test liquid stream.

Fig. 1 is depicted without the associate members such as the higher-order of oscillation electric signal generator.

The Micropump 14 can be customized to specialized factory.

Its connected mode with various micro-fluidic chip of various Micropump is known.

Described its main body of hinge-type fixture can simply be changed a social system using commercially available hinge；It can also be customized to hardware processing factory.

Involved miniature ultrasonic transducer units 5 are commercially available；It can also be customized to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal transmission cable 4 is commercially available；Can also 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；It can also be customized to relevant manufacturers.

Its inner passage of the micro-fluidic chip involved by this case is the pipeline of hydrophobic capillary form.

The Micropump both can be the Micropump of external form；The Micropump can also be done into or say inside the embedded micro-fluidic chip The Micropump of the built in version of its sample introduction end structure position or the sample introduction end Near-neighbor Structure position, its basic structure key element and external form Micropump it is identical.Micropump in legend is the Micropump of external form.

The multiple tracks electrochemical workstation is commercially available；The multiple tracks electrochemical workstation can also be according to specific needs to related special Industry producer customizes.

In view of this case pipeline of the presentation parallel construction its form that related text expresses that it is described above is clear enough It is clear, the concrete form of the pipeline in this kind of micro-fluidic chip of this case is no longer specifically illustrating in this case embodiment.

Antibody described in this case refers to the antibody of broad sense；Antigen described in this case refers to the antigen of broad sense；It is immunized described in this case multiple Compound refers to the immune complex of broad sense.

Claims (10)

1. using PDMS as the co-detections of tumor markers in benign chip apparatus of the dual drive of substrate, it is characterised in that the structure bag of the device Micro-fluidic chip is included, the structure of the micro-fluidic chip includes the substrate and cover plate of installing bonded to each other together, the substrate and lid Piece is plate object or tablet, and what is formed via mould pressing process or etching technics contained in that face towards the cover plate of the substrate Channel structure, substrate bonded to each other being installed together has been built into the micro-fluidic core containing pipeline configuration jointly with the cover plate Piece, the locations of structures of the pipeline is located at the substrate and cover plate juncture area bonded to each other, and the two ends of the pipeline are micro- with this respectively The sample introduction end of fluidic chip and terminal connection, the sample introduction end is the injection end of the micro-fluidic chip sample solution, and the terminal is this The terminal that sample solution flows in its chip when the actual sample introduction of micro-fluidic chip is tested, the terminal is located remotely from each other with the sample introduction end, should The distance between terminal and the sample introduction end are in order or inverse on diverse location in the pipeline between 3 centimetres and 10 centimetres Sequence is equiped with working electrode and to electrode and reference electrode, and the order refers to that its locations of structures of the reference electrode is more leaned on The nearly terminal location, the backward refers to the reference electrode locations of structures closer to the sample introduction end position, the work Electrode is made up of conductive electrode and the gold size sensitive membrane for having embedded tumor markers antibody being attached on the conductive electrode, Parallel construction is presented in the construction of the pipeline, and the pipeline in parallel construction is made up of six lateral parallel connections, and the presentation is simultaneously Its appearance profile of the pipeline of connection construction is similar to the profile of parallel circuit, and the quantity of the working electrode is six, this six The installation position of working electrode is located in six laterals respectively, and, its top layer gold size of six working electrodes is sensitive Tumor markers antibody in membrane structure is the six kinds of tumor markers antibody that can be specifically bound to tumor markers antigen respectively Material, six kinds of antibody materials are tumor markers antibody A FP, CEA, PSA, CA125, CA19-9 and CA15-3 respectively, The antigen is the antigen of broad sense, and the antibody is the antibody of broad sense, and its material of the working electrode is argent material, gold Column, sheet or thread is presented in material, carbon material or thermal decomposition conducting polymer material, its pattern of the working electrode, should Its material of substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, the surface of the primary form its It is intended to refer to not by any surface chemical modification or the surface of the primary form of the material of any surface chemical modification, should The structure of device also includes hinge-type fixture, hinge-type fixture its appearance profile likeness in form hinge, and the hinge-type fixture is by mutually cutting with scissors Two hinges being connected together and matched through a fastening screw of two hinges and one with the fastening screw and with The nut for being used for fastening and hand break loose manually that the fastening screw connects together is constituted, and two hinges of the hinge-type fixture are each Mutually drawn close with its tip and clamp the micro-fluidic chip, the tip is positioned at the knot of the neighbouring terminal of the micro-fluidic chip Fixation, which is attached, on structure position, in a hinge at least in is equiped with miniature ultrasonic transducer units, and, high frequency vibrating Electric signal transmission cable is swung, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable link together； The hinge-type fixture facilitates the function that the device is disassembled there is provided one；Its major function of the miniature ultrasonic transducer units is in miniflow When controlling the actual sample introduction of chip and testing, the ultrasonic wave launched using it reduces sample solution and its inner passage of the micro-fluidic chip Inwall between interfacial tension, can be compatible, also, utilize the sample introduction end and the terminal and the miniature ultrasonic Difference in the distance between wave transducer installation position difference and its ultrasonic intensity experienced, enters described in induced synthesis Interfacial tension between difference between its interfacial tension of sample end and the terminal its interfacial tension, the micro-fluidic chip two ends is poor Different to form pressure gap between the two ends of the micro-fluidic chip, the pressure gap can drive sample solution to the terminal stream It is dynamic；Its function of the miniature ultrasonic transducer units also includes checking large biological molecule contained in sample with its ultrasonic wave launched Its absorption on the micro-fluidic chip its inner passage inner surface, and then check the substrate of the dimethyl silicone polymer material its body With respect to the effect of swallowing up of the large biological molecule；It is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function include with Its property to the strong absorption of ultrasonic wave, is absorbed strongly to ultrasonic wave, and thereby in the micro-fluidic chip, the terminal is entered to this The rapid decrement of ultrasonic intensity is realized within limited short distance between sample end；And, Micropump, the Micropump and the sample introduction end Connection；The function of the Micropump is, the interfacial tension between the inwall of the sample solution and its inner passage of micro-fluidic chip by The ul-trasonic irradiation and reduce, under the increased precondition of alternate compatibility, come super with this with the mechanicalness pumping strength of the Micropump Interfacial tension difference its driving force brought between the two ends of sound wave induction supports mutually, adjustment, mutual coupling mutually Close, the strength that one driving test liquid flows to the terminal direction flowing is pooled in the way of Collaboration；The cover plate and base Its thickness of piece is between 1.0 millimeters and 5.0 millimeters；And, ultrasonic wave damper, its profile of the ultrasonic wave damper is in Block, tabular or bar-shaped；Its material of the ultrasonic wave damper is microcellular rubber, sponge rubber or microporous polyurethane elastomer；With And, elastic clip, the elastic force accompanies two clamping limbs, and the medial surface of each clamping limb is relative with the medial surface of another clamping limb, The medial surface of one of clamping limb is close to the sample introduction end of the micro-fluidic chip, and the medial surface of another clamping limb is close to this and surpassed Sound wave damper, the elastic clip is bonded to each other by the sample introduction end of the micro-fluidic chip and the ultrasonic wave damper with its gripping strength Clip together, the strong consumption to ultrasonic wave that the ultrasonic wave damper is brought with its material, further support micro- at this The fluidic chip terminal is thereby entered to realizing the rapid decrement of ultrasonic intensity within the limited short distance between the sample introduction end One step expands the difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension.

2. the co-detections of tumor markers in benign chip apparatus according to claim 1 using PDMS as the dual drive of substrate, its feature It is, it is capillary channel that the pipeline, which includes the lateral,.

3. the co-detections of tumor markers in benign chip apparatus according to claim 1 using PDMS as the dual drive of substrate, its feature Be, the thermal decomposition conducting polymer be by polyimides or polyacrylonitrile be heat-treated through anoxybiotic after the conductive material that is formed.

4. the co-detections of tumor markers in benign chip apparatus according to claim 1 using PDMS as the dual drive of substrate, its feature Be, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the working electrode Length is between 1 micron to 15000 microns.

5. the co-detections of tumor markers in benign chip apparatus according to claim 1 using PDMS as the dual drive of substrate, its feature It is, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.

6. the co-detections of tumor markers in benign chip apparatus according to claim 1 using PDMS as the dual drive of substrate, its feature It is, its material of the cover plate in structure is dimethyl silicone polymer material.

7. the co-detections of tumor markers in benign chip apparatus according to claim 1 using PDMS as the dual drive of substrate, its feature It is, the Micropump is miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.

8. the co-detections of tumor markers in benign chip apparatus according to claim 1 using PDMS as the dual drive of substrate, its feature It is, the microcellular rubber is micropore silicon rubber or micropore fluorubber.

9. the co-detections of tumor markers in benign chip apparatus according to claim 1 using PDMS as the dual drive of substrate, its feature Be, the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission cable its The other end is connected with the higher-order of oscillation electric signal generator.

10. the co-detections of tumor markers in benign chip apparatus according to claim 1 using PDMS as the dual drive of substrate, it is special Levy and be, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 5 milliwatts and 5000 milliwatts, and this is miniature The frequency of its ultrasonic wave operationally launched of ultrasonic transducer is between 100KHz and 12MHz.