CN107233938A

CN107233938A - The tumor markers joint-detection six-channel microfluidic chip device simplified

Info

Publication number: CN107233938A
Application number: CN201610220017.7A
Authority: CN
Inventors: 李榕生
Original assignee: Individual
Current assignee: Individual
Priority date: 2016-03-29
Filing date: 2016-03-29
Publication date: 2017-10-10

Abstract

The present invention relates to a kind of tumor markers joint-detection six-channel microfluidic chip device simplified, 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, while there are a series of problems for needing to overcome；This case is directed to the serial problem.This case main points are, the selected PDMS with ecosystem surface of substrate, and the chain ring type magnetic holding device for being equiped with miniature ultrasonic transducer units is socketed is positioned at the test liquid stream terminal of the micro-fluidic chip its neighbor positions, 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, thereby facilitate test liquid stream to be flowed along originally hydrophobic capillary channel to terminal direction.The device exempts to use Micropump completely.

Description

The tumor markers joint-detection six-channel microfluidic chip device simplified

Technical field

The present invention relates to a kind of tumor markers joint-detection six-channel microfluidic chip device simplified, belong to analysis test neck Domain.

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.

The content of the invention

The technical problems to be solved by the invention are to provide a package solution, solve what is addressed above totally Two problems, also, by the solution be applied to build it is a kind of it is new can be for six kinds than more typical primary tumor mark Will thing carries out 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 tumor markers simplified Joint-detection six-channel microfluidic chip device, the program is characterized in that the structure of the device includes multichannel micro-fluidic chip, The structure of the micro-fluidic chip includes installing substrate and cover plate together bonded to each other, the substrate and cover plate be plate object or Contain the channel structure via mould pressing process or etching technics formation, the base in tablet, that face towards the cover plate of the substrate Piece also contains and is connected and pierces being formed via mould pressing process, etching technics or simple drilling technology for the substrate with the channel structure Window structure, substrate bonded to each other being installed together and the cover plate have been built into containing pipeline configuration and phase therewith jointly The micro-fluidic chip of liquid pool structure even, the locations of structures of the pipeline is located at the substrate and cover plate interface zone bonded to each other, Its side of the window is blocked by the cover plate and opposite side is opened, and the locations of structures of the window is exactly the locations of structures of the liquid pool, institute Stating liquid pool has two kinds, and two kinds of liquid pools are the sample introduction end liquid pool and terminal liquid pool positioned at different structure position respectively, and this is micro-fluidic The sample introduction end position of chip has one or more sample introduction end liquid pool, and the sample introduction end refers to that the micro-fluidic chip is real The injection end position of detected solution during the sample introduction of border, then has a terminal liquid pool in the terminal location of the micro-fluidic chip, described Terminal refers to the terminal location of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, the terminal and the sample introduction end It is located remotely from each other, one end of the pipeline and the sample introduction end liquid pool UNICOM positioned at sample introduction end, the other end of the pipeline are micro- with being located at this The terminal liquid pool UNICOM of the terminal of fluidic chip, and, sequentially or backward be respectively installed in the pipeline it is different Working electrode on position and to electrode and reference electrode, 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 having six links in chain ring type magnetic holding device, its structure of the chain ring type magnetic holding device, and the link is equal In strip, shaft-like or bar-shaped, each adjacent link is hinged to form chain link, the hexagonal cyclic structure of its appearance profile of the chain link, Its locations of structures of each drift angle of the hexagonal annular structure is articulated structure position, two therein of the hexagonal annular structure Its material of link in opposite side position is magnetic conductivity material, the equal right and wrong of its material of the remaining four processes of the hexagonal annular structure Magnetic material, the non magnetic material refers to the material not responded strongly to externally-applied magnetic field, two rings of the magnetic conductivity material Magnet exciting coil is wound with a link among section, this is wound with both sides neighbour position of the link in its magnet exciting coil of magnet exciting coil The pole shoe for being respectively equiped with a magnetic conductivity material is put, two pole shoes are had, two pole shoes are directed to another magnetic conductivity Fixation is attached on the link of material, its surface of the link of another magnetic conductivity material and is equiped with miniature ultrasonic transducer units, is relied on The chain ring type magnetic holding device socket of electromagnetism adhesive strength is positioned at the close position of its terminal of the micro-fluidic chip, and, Higher-order of oscillation electric signal transmission cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable are connected to Together；The chain ring type magnetic holding device facilitates the function that the device is disassembled there is provided one；Its main work(of the miniature ultrasonic transducer units Can be in the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it reduce sample solution with the pipeline Interfacial tension between wall, can be compatible, also, is changed using the sample introduction end and the terminal with the miniature ultrasonic Difference in the distance between energy device installation position difference and its ultrasonic intensity experienced, sample introduction end described in induced synthesis Interfacial tension difference meeting between difference between its interfacial tension and the terminal its interfacial tension, the micro-fluidic chip two ends Pressure gap is formed between the two ends of the micro-fluidic chip, the pressure gap can drive sample solution to the end flow； The miniature ultrasonic transducer units its functions also include with its ultrasonic wave launched check large biological molecule contained in sample its Absorption on the inner surface of pipeline, and then check the substrate of the dimethyl silicone polymer material its body phase to the large biological molecule The effect of swallowing up；Its function of the substrate of the dimethyl silicone polymer material is included with cover plate and working electrode and to electrode and reference Electrode together builds the micro-fluidic chip, it is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function also 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, ultrasonic wave damper, the ultrasonic wave Its profile of damper is in block, tabular or bar-shaped；Its material of the ultrasonic wave damper is microcellular rubber, sponge rubber or polyurethane Micro-pore elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, the medial surface of each clamping limb and another clamping limb Medial surface it is relative, the medial surface of one of clamping limb is close to the sample introduction end of the micro-fluidic chip, another clamping limb it is interior The ultrasonic wave damper is close in side, and the elastic clip is disappeared the sample introduction end of the micro-fluidic chip and the ultrasonic wave with its gripping strength Subtract device to clip together bonded to each otherly, the strong consumption to ultrasonic wave that the ultrasonic wave damper is brought with its material is entered One step is supported to realize the fast of ultrasonic intensity within micro-fluidic chip terminal to the limited short distance between the sample introduction end Quick depletion, and thereby further expand the difference between described its interfacial tension of sample introduction end 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.

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

The word of magnetic conductivity material one art-recognized meanings of itself are known；Belong to magnetic conductivity material material such as pure iron, Silicon steel, soft magnetic ferrite etc..

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

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

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 related to several liquid pools in this case microfluidic chip structure, the liquid pool is the pond shape or scrotiform structure for transitional liquid storage Make, its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, the cavity shape such as cylindrical empty Cavity-like, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..

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；Together Sample, the technology of hole-opening is even more known simple technique on naked PDMS substrates.This case is not also to this expansion superfluous words.

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 9000 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.

The preferred scope of the distance between the terminal and the sample introduction end is between 3 centimetres and 10 centimetres.

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 basis Need the arbitrary size of setting.

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：

Proposed first based on this case and the first public New stream driving principle, its application running of this case micro-fluidic chip In, the New stream driving method is determined completely without involving any additional Micropump.

The interfacial tension difference of this case to be formed between micro-fluidic chip two ends caused by the ultrasonic wave, drives liquid Stream flows in the capillary channel of the six-channel microfluidic chip, using multi-channel electrochemical analyzer device respectively to six kinds of typical cases Tumor markers antigen carries out joint-detection.

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

1st, blood serum sample liquid is added in micro-pipe road, under ultrasonic wave driving, various tumor markers antigen molecules are each In passage on electrode surface gold size sensitive membrane embed corresponding horseradish peroxidase-labeled tumor markers 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 relies on the socket of electromagnetism adhesive strength fixed in the terminal of the micro-fluidic chip Position described in chain ring type magnetic holding device, with the chain ring type magnetic holding device one magnetic conductivity link attaching installation miniature ultrasonic Wave transducer, the low-power launched using it, the ultrasonic wave of high-frequency band so that without surface chemical modification or come to the surface The compatibility learned between strong hydrophobic its tube wall of micro-fluidic chip internal pipeline and the test object aqueous solution of modification significantly increases Plus, this is test liquid stream by there is provided a realistic possibility；Meanwhile, using dimethyl silicone polymer substrate its to ultrasound The strong absorbability of ripple, in shorter distance, it is, from the terminal to only several centimeters the sample introduction end In the very short distance of yardstick, reach the rapid decrement of ultrasonic intensity, thereby cause institute at the two ends of the micro-fluidic chip The difference of interfacial tension is stated, and then, utilize the pressure between its two ends for being formed of the difference of the interfacial tension between the two ends Difference, driving test liquid stream flows in the strong hydrophobic capillary channel of such a script to the terminal direction.By this Case liquid stream drive scheme, entirely without any come to the surface must be carried out to the substrate and its internal pipeline of the dimethyl silicone polymer material Modification or chemical modification are learned, the laborious procedures of the surface chemical modification or chemical modification have been altogether dispensed with；And altogether dispense with biography The equipment of Micropump in meaning of uniting etc；On the other hand, the ultrasonic wave of the low-power, high-frequency band, additionally it is possible to contain in sample Absorption of the large biological molecule on literalness naked its inner surface of pipeline of dimethyl silicone polymer substrate, and then contain that this gathers Swallow up effect of its body phase of dimethyl siloxane piece to the large biological molecule；The antigen, antibody and antigen and antibody Reversible binding thing is all the type for belonging to described large biological molecule certainly；Due to described suction-operated and the described work that swallows up With effectively being contained, therefore, dependence test result will be better able to objectively reflect actual conditions；The low-power, height are again and again The effect of section ultrasonic wave, also includes facilitating what the Reversible binding between antigen, antibody react quickly to reach, this causes correlation certainly Test operation can be with than the completion of faster speed.

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

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 Said on the sport technique segment that ultrasonic intensity rapid decrement is realized in the such short distance in sample introduction end, its effect of the ultrasonic wave damper is suitable In the size expansion device of micro-fluidic chip, in other words, the ultrasonic wave damper its function as and significantly extend miniflow Its terminal of chip is controlled the distance between to sample introduction end, is the equal of from several centimetres of extension of script to more than ten centimetres of length Or twenties centimetres of length or longer length, so so that described terminal to the ultrasonic wave between sample introduction end in short distance The sport technique segment of intensity rapid decrement can relatively easily be reached, also, the size expansion device namely the ultrasonic wave damper Its installation and removal is all very convenient, it is important that it can also be reused.

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, this kind very cheap polydimethyl siloxane material is just possible in the micro-fluidic chip Prepare, production, using etc. field play bigger effect.

Fixation is attached in the chain ring type magnetic holding device one magnetic conductivity link in this case structure and has installed the miniature ultrasonic Transducer, the function that the device is disassembled is facilitated this architecture provides one, in this way, the chain ring type magnetic holding device is led together with one The miniature ultrasonic transducer units attached in magnetic link just easily can be mutually disengaged with the micro-fluidic chip, then, the portion The component that dividing freely to depart from is reused many times in which just can circulate benignly；The architectural feature is conducive to saving making for the device Use cost.

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 be this case device chain ring type magnetic holding device its with outside side view rough under the micro-fluidic chip socket state, The legend and indicate the relative position relation under the socket state between each component.

Fig. 2 is the outside side view under another viewing angle of this case device；Fig. 2 viewing angle and Fig. 1 sight Angle is examined to be mutually perpendicular to.

In figure, 1 is chain ring type magnetic holding device, and 2 be the terminal of the micro-fluidic chip, and 3 be the described of the micro-fluidic chip Sample introduction end, 4 be the substrate of dimethyl silicone polymer material, and 5 be cover plate, and 6 be miniature ultrasonic transducer units, and 7 be high frequency vibrating Electric signal transmission cable is swung, 8,15 be the link of two magnetic conductivity materials positioned at different structure position, two magnetic conductions respectively Property material link end-to-end relation each other in the structure shown here, 9,22 be two pole shoes positioned at different structure position respectively, 10, 12nd, 14,17,19,21 be six pin joints in six diverse locations respectively, and 11,13,18,20 be place respectively In the link of four non magnetic materials of four diverse locations, 16 be magnet exciting coil；The chain ring type electromagnetic clamp in legend is signed an undertaking Structure is only the legend structure of signal, and the actual chain ring type magnetic holding device structure is not limited to the legend chain ring type magnetic holding device structure；Figure Example in arrow indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, the flowing of its test liquid stream Direction.It is depicted without being also depicted without the elastic clip in the ultrasonic wave damper, legend in legend.

Embodiment

In this case that Fig. 1 and Fig. 2 are shown embodiment, its main points of the example are, it is micro- that the structure of the device includes multichannel Fluidic chip, the structure of the micro-fluidic chip includes the substrate 4 and cover plate 5 of installing bonded to each other together, the He of substrate 4 Cover plate 5 is plate object or tablet, and that face towards the cover plate 5 of the substrate 4 is contained via mould pressing process or etching work Skill formation channel structure, the substrate 4 also containing be connected with the channel structure and pierce the substrate 4 via mould pressing process, Etching technics or the window structure of simple drilling technology formation, substrate 4 bonded to each other being installed together and the cover plate 5 are common The micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto is built into, the locations of structures of the pipeline is located at the base Piece 4 and the cover plate 5 interface zone bonded to each other, its side of the window is blocked by the cover plate 5 and opposite side is opened, the window Locations of structures be exactly the liquid pool locations of structures, the liquid pool has two kinds, and two kinds of liquid pools are to be located at different structure position respectively There is the one or more sample introduction sample introduction end liquid pool and terminal liquid pool put, the position of sample introduction end 3 of the micro-fluidic chip Liquid pool is held, the sample introduction end 3 refers to the injection end position of detected solution during the micro-fluidic chip actual sample introduction, micro-fluidic at this Then there is a terminal liquid pool position of terminal 2 of chip, when the terminal 2 refers to that the actual sample introduction of the micro-fluidic chip is tested The terminal location that liquid flows in its chip, the terminal 2 is located remotely from each other with the sample introduction end 3, and one end of the pipeline is with being located at sample introduction The sample introduction end liquid pool UNICOM at end 3, the other end of the pipeline and the terminal of the terminal 2 positioned at the micro-fluidic chip Liquid pool UNICOM, and, sequentially or backward be respectively installed in working electrode in the pipeline on diverse location and to electrode with And reference electrode, the order refers to its locations of structures of the reference electrode closer to the position of terminal 2, and the backward refers to Be the reference electrode locations of structures closer to the position of sample introduction end 3, the working electrode is by conductive electrode and attaching The gold size sensitive membrane for having embedded tumor markers antibody on the conductive electrode is constituted, and structure in parallel is presented in the construction of the pipeline Make, the pipeline in parallel construction is made up of six lateral parallel connections, its profile of the pipeline of the presentation parallel construction Profile is similar to the profile of parallel circuit, and the quantity of the working electrode is six, the installation position difference of six working electrodes In six laterals, and, the tumor markers in the sensitive membrane structure of its top layer gold size of six working electrodes resists Body is the six kinds of tumor markers antibody materials that can be specifically bound to tumor markers antigen respectively, six kinds of antibody materials difference It is tumor markers antibody A FP, CEA, PSA, CA125, CA19-9 and CA15-3, the antigen is the antigen of broad sense, institute The antibody that antibody is broad sense is stated, its material of the working electrode is that argent material, gold material, carbon material or thermal decomposition are led Column, sheet or thread is presented in electric macromolecule material, the working electrode its pattern, and its material of the substrate 4 is poly dimethyl silicon Oxygen alkane material, its surface of substrate 4 is the surface of primary form, the surface of the primary form its be intended to refer to not by appointing The surface of the primary form of what surface chemical modification or the material of any surface chemical modification, the structure of the device also includes chain link Have six links in formula magnetic holding device 1, its structure of the chain ring type magnetic holding device 1, six links be respectively link 8,11, 13rd, 15,18,20, the link 8,11,13,15,18,20 is in strip, shaft-like or bar-shaped, each adjacent link Be hinged to form chain link, the hexagonal cyclic structure of its appearance profile of the chain link, each drift angle of the hexagonal annular structure its Locations of structures 10,12,14,17,19,21 is articulated structure position, and two therein of the hexagonal annular structure is in Its material of the link 8,15 of opposite side position is magnetic conductivity material, the remaining four processes 11 of the hexagonal annular structure, 13, 18th, 20 its material are non-magnetic materials, and the non magnetic material refers to the material not responded strongly to externally-applied magnetic field, Magnet exciting coil 16 is wound with a link 15 among two links of the magnetic conductivity material, this is wound with magnet exciting coil 16 Link 15 pole shoe 9,22 of a magnetic conductivity material is respectively equiped with the both sides neighbor positions of its magnet exciting coil 16, have Two pole shoes 9,22, two pole shoes 9,22 are directed to the link 8 of another magnetic conductivity material, another magnetic conduction Property its surface of the link 8 of material on attach fixed chain link for being equiped with miniature ultrasonic transducer units 6, relying on electromagnetism adhesive strength Formula magnetic holding device 1 is socketed the close position for being positioned at its terminal 2 of the micro-fluidic chip, and, higher-order of oscillation electric signal is passed Transmission cable 7, one end of the higher-order of oscillation electric signal transmission cable 7 links together with the miniature ultrasonic transducer units 6；The chain Ring type magnetic holding device 1 facilitates the function that the device is disassembled there is provided one；Its major function of the miniature ultrasonic transducer units 6 be During the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it is reduced between sample solution and the inwall of the pipeline Interfacial tension, can be compatible, also, utilize the sample introduction end 3 and the terminal 2 and the miniature ultrasonic transducing Difference in the distance between the installation position of device 6 difference and its ultrasonic intensity experienced, sample introduction end described in induced synthesis Interface between difference between 3 its interfacial tension and the terminal 2 its interfacial tension, the micro-fluidic chip two ends 2,3 Tension difference can form pressure gap between the two ends 2,3 of the micro-fluidic chip, and the pressure gap can drive sample solution Flowed to the terminal 2；Its function of the miniature ultrasonic transducer units 6 also includes checking institute in sample with its ultrasonic wave launched Its absorption on the inner surface of pipeline of the large biological molecule contained, and then check the substrate 4 of the dimethyl silicone polymer material Swallow up effect of its body phase to the large biological molecule；Its function of the substrate 4 of the dimethyl silicone polymer material includes and cover plate 5 And working electrode and the micro-fluidic chip is together built to electrode and reference electrode, soft dimethyl silicone polymer for simultaneously having elasticity The substrate 4 of material its function also includes, with its property to the strong absorption of ultrasonic wave, ultrasonic wave being absorbed strongly, and thereby The fast express delivery of ultrasonic intensity is realized within micro-fluidic chip terminal 2 to the limited short distance between the sample introduction end 3 Subtract；And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；The ultrasonic wave damper its Material is microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, The medial surface of each clamping limb is relative with the medial surface of another clamping limb, and the medial surface of one of clamping limb is close to the miniflow The sample introduction end 3 of chip is controlled, the medial surface of another clamping limb is close to the ultrasonic wave damper, and the elastic clip is with its gripping strength By the sample introduction end 3 of the micro-fluidic chip and the ultrasonic wave damper it is bonded to each other clip together, the ultrasonic wave damper is with its material The strong consumption to ultrasonic wave that matter is brought, further supports that the terminal 2 arrives the sample introduction end 3 in the micro-fluidic chip Between limited short distance within realize the rapid decrement of ultrasonic intensity, and thereby further expand described its boundary of sample introduction end 3 Difference between face tension force and the terminal 2 its interfacial tension.

It is depicted without being also depicted without the elastic clip in the ultrasonic wave damper, legend in legend.

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

The associate members such as the higher-order of oscillation electric signal generator and multiple tracks electrochemical workstation are depicted without in Fig. 1 and Fig. 2.

Involved miniature ultrasonic transducer units 6 are commercially available；It can also be customized to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal transmission cable 7 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.

Each working electrode in this example structure and electrode and reference electrode via each special cable or can be said respectively Get lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as annex or saying interface connection of getting lines crossed.

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

1. the tumor markers joint-detection six-channel microfluidic chip device simplified, it is characterised in that the structure bag of the device Multichannel 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 base Piece and cover plate are plate object or tablet, and that face towards the cover plate of the substrate is contained via mould pressing process or etching technics The channel structure of formation, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etch work Skill or the window structure of simple drilling technology formation, substrate bonded to each other being installed together has been built into jointly with the cover plate to be contained The micro-fluidic chip of liquid pool structure for having pipeline configuration and being attached thereto, the locations of structures of the pipeline is located at the substrate and the cover plate Interface zone bonded to each other, its side of the window is blocked by the cover plate and opposite side is opened, and the locations of structures of the window is exactly institute State the locations of structures of liquid pool, the liquid pool has two kinds, two kinds of liquid pools respectively be positioned at different structure position sample introduction end liquid pool with And terminal liquid pool, the sample introduction end position of the micro-fluidic chip has one or more sample introduction end liquid pool, the sample introduction end The injection end position of detected solution during the micro-fluidic chip actual sample introduction is referred to, then has one in the terminal location of the micro-fluidic chip The individual terminal liquid pool, the terminal refers to the terminal position of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested Put, the terminal is located remotely from each other with the sample introduction end, one end of the pipeline and the sample introduction end liquid pool UNICOM positioned at sample introduction end, the pipe The other end in road with positioned at the micro-fluidic chip the terminal the terminal liquid pool UNICOM, and, sequentially or backward point The working electrode that is not installed in the pipeline on diverse location and to electrode and reference electrode, the order refers to the ginseng Than its locations of structures of electrode closer to the terminal location, the backward refers to the reference electrode locations of structures closer to described Sample introduction end position, the working electrode is resisted by conductive electrode and the tumor markers that embedded being attached on the conductive electrode The gold size sensitive membrane of body is constituted, and parallel construction is presented in the construction of the pipeline, and the pipeline in parallel construction is by six laterals 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 working electrode Quantity be six, the installation positions of six working electrodes is located in six laterals respectively, and, six works The tumor markers antibody made in the sensitive membrane structure of its top layer gold size of electrode is that tumor markers antigen can be specifically bound respectively 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 is the antigen of broad sense, and the antibody is the antibody of broad sense, its material of the working electrode It is argent material, gold material, carbon material or thermal decomposition conducting polymer material, post is presented in its pattern of the working electrode Shape, sheet or thread, its material of the substrate are dimethyl silicone polymer materials, and its surface of the substrate is the surface of primary form, The surface of the primary form its be intended to refer to the material not no by any surface chemical modification or any surface chemical modification Primary form surface, the structure of the device also includes chain ring type magnetic holding device, is had in its structure of the chain ring type magnetic holding device Six links, the link is in strip, shaft-like or bar-shaped, and each adjacent link is hinged to form chain link, its profile of the chain link The hexagonal cyclic structure of profile, its locations of structures of each drift angle of the hexagonal annular structure is articulated structure position, and this six Two therein of side shape cyclic structure is magnetic conductivity material in the link of opposite side position its material, the hexagonal annular structure it is remaining Lower its material of four processes is non-magnetic material, and the non magnetic material refers to the material not responded strongly to externally-applied magnetic field Magnet exciting coil is wound with a link among matter, two links of the magnetic conductivity material, this is wound with the link of magnet exciting coil The pole shoe of a magnetic conductivity material is respectively equiped with the both sides neighbor positions of its magnet exciting coil, two pole shoes are had, this two Individual pole shoe is directed to the link of another magnetic conductivity material, and fixed installing is attached on its surface of the link of another magnetic conductivity material There are miniature ultrasonic transducer units, rely on the chain ring type magnetic holding device socket of electromagnetism adhesive strength to be positioned at its institute of the micro-fluidic chip State the close position of terminal, and, higher-order of oscillation electric signal transmission cable, one end of the higher-order of oscillation electric signal transmission cable with The miniature ultrasonic transducer units link together；The chain ring type magnetic holding device facilitates the function that the device is disassembled there is provided one；Should Its major function of miniature ultrasonic transducer units is that in the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it is dropped Interfacial tension between the inwall of low sample solution and the pipeline, can be compatible, also, using the sample introduction end and In the distance between the terminal and the miniature ultrasonic transducer units installation position difference and its ultrasonic intensity experienced Difference, the difference between its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension, the micro-fluidic chip Interfacial tension difference between the two ends can form pressure gap between the two ends of the micro-fluidic chip, and the pressure gap can drive Sample solution is moved to the end flow；Its function of the miniature ultrasonic transducer units also includes checking examination with its ultrasonic wave launched Its absorption on the inner surface of pipeline of contained large biological molecule in sample, and then check the dimethyl silicone polymer material Swallow up effect of its body phase of substrate to the large biological molecule；Its function of the substrate of the dimethyl silicone polymer material includes and cover plate And working electrode and the micro-fluidic chip is together built to electrode and reference electrode, soft dimethyl silicone polymer for simultaneously having elasticity The substrate of material its function also includes, with its property to the strong absorption of ultrasonic wave, ultrasonic wave being absorbed strongly, and thereby exists The micro-fluidic chip terminal is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end；With 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 Microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, each folder The medial surface of gripping arm is relative with the medial surface of another clamping limb, and the medial surface of one of clamping limb is close to the micro-fluidic chip Sample introduction end, the medial surface of another clamping limb is close to the ultrasonic wave damper, and the elastic clip is with its gripping strength by the miniflow Sample introduction end and the ultrasonic wave damper for controlling chip 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 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 thereby further expand described its interfacial tension of sample introduction end and the terminal its Difference between interfacial tension.

2. the tumor markers joint-detection six-channel microfluidic chip device according to claim 1 simplified, its feature It is, it is capillary channel that the pipeline, which includes the lateral,.

3. the tumor markers joint-detection six-channel microfluidic chip device according to claim 1 simplified, 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 tumor markers joint-detection six-channel microfluidic chip device according to claim 1 simplified, 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 tumor markers joint-detection six-channel microfluidic chip device according to claim 1 simplified, its feature It is, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.

6. the tumor markers joint-detection six-channel microfluidic chip device according to claim 1 simplified, its feature It is, its material of the cover plate in structure is dimethyl silicone polymer material.

7. the tumor markers joint-detection six-channel microfluidic chip device according to claim 1 simplified, its feature It is, the distance between the terminal and the sample introduction end are between 3 centimetres and 10 centimetres, its thickness of the cover plate and substrate Degree is between 1.0 millimeters and 5.0 millimeters.

8. the tumor markers joint-detection six-channel microfluidic chip device according to claim 1 simplified, its feature It is, the microcellular rubber is micropore silicon rubber or micropore fluorubber.

9. the tumor markers joint-detection six-channel microfluidic chip device according to claim 1 simplified, 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 tumor markers joint-detection six-channel microfluidic chip device according to claim 1 simplified, its feature It is, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 5 milliwatts and 9000 milliwatts, and this is miniature super The frequency of its ultrasonic wave operationally launched of acoustic wave transducer is between 100KHz and 12MHz.