CN107282156A - A kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes - Google Patents

Abstract

The present invention relates to a kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes, belong to analysis testing field.The substrate for eight kinds of classifiable tumor markers in detecting micro-fluidic chips that women is applicable is made so that PDMS is dimethyl silicone polymer, it is advantageous, there is problem；This case is directed to the 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, 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

A kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes

Technical field

The present invention relates to a kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes, 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.

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 It can especially need seven kinds paid close attention to than more typical primary tumor mark progress examination simultaneously, simultaneously for belonging to women physical examination 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 suitable for women physical examination examination The co-detections of tumor markers in benign chip apparatus of purposes, it is characterised in that the structure of the device includes micro-fluidic chip, the micro-fluidic core The structure of piece includes the substrate and cover plate of installing bonded to each other together, and the substrate and cover plate are plate object or tablet, are somebody's turn to do The channel structure via mould pressing process or etching technics formation is contained in that face towards the cover plate of substrate, bonded to each other to be arranged on The substrate together has been built into the micro-fluidic chip containing pipeline configuration jointly with the cover plate, and the locations of structures of the pipeline is located at should Substrate and cover plate juncture area bonded to each other, the two ends of the pipeline connect with the sample introduction end of the micro-fluidic chip and terminal respectively Connect, the sample introduction end is the injection end of the micro-fluidic chip sample solution, when the terminal is the micro-fluidic chip actual sample introduction test its The terminal that sample solution flows in chip, the terminal is located remotely from each other with the sample introduction end, and the distance between the terminal and the sample introduction end are situated between 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 its locations of structures of the reference electrode closer to the terminal location, and the backward refers to Be the reference electrode locations of structures closer to the sample introduction end position, the working electrode is by conductive electrode and is attached to The gold size sensitive membrane for having embedded tumor markers antibody on the conductive electrode is constituted, and parallel construction is presented in the construction of the pipeline, The pipeline in parallel construction is made up of eight lateral parallel connections, its appearance profile of the pipeline of the presentation parallel construction It is similar to the profile of parallel circuit, the quantity of the working electrode is eight, and the installation position of eight working electrodes is located at respectively In eight laterals, and, the tumor markers antibody point in the sensitive membrane structure of its top layer gold size of eight working electrodes It is not the eight kinds of tumor markers antibody materials that can be specifically bound to tumor markers antigen, eight kinds of antibody materials are swollen respectively Tumor markers antibody CA199, CA153, CA125, CA242, AFP, CEA, EB and β-HCG, the antigen is broad sense Antigen, the antibody is the antibody of broad sense, its material of the working electrode be argent material, gold material, carbon material or Conducting polymer material is thermally decomposed, column, sheet or thread is presented in its pattern of the working electrode, and its material of the substrate is poly- two Methylsiloxane 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 pass through The surface of the primary form of the material of any surface chemical modification or any surface chemical modification is crossed, the structure of the device also includes Six links are had in chain ring type magnetic holding device, its structure of the chain ring type magnetic holding device, the link is in strip, shaft-like or rod Shape, each adjacent link is hinged to form chain link, the hexagonal cyclic structure of its appearance profile of the chain link, the hexagonal annular knot Its locations of structures of each drift angle of structure is articulated structure position, and two therein of the hexagonal annular structure is in opposite side position Its material of link is magnetic conductivity material, and its material of the remaining four processes of the hexagonal annular structure is non-magnetic material, described Non magnetic material refers to a ring among the material not responded strongly to externally-applied magnetic field, two links of the magnetic conductivity material Magnet exciting coil is wound with section, this is wound with the link of magnet exciting coil and is respectively equiped with one in the both sides neighbor positions of its magnet exciting coil The pole shoe of individual magnetic conductivity material, has two pole shoes, and two pole shoes are directed to the link of another magnetic conductivity material, should Attach to fix on its surface of the link of another magnetic conductivity material and be equiped with miniature ultrasonic transducer units, rely on electromagnetism adhesive strength The chain ring type magnetic holding device is socketed the close position for being positioned at its terminal of the micro-fluidic chip, and, higher-order of oscillation electric signal Transmission cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable link together；The chain ring type Magnetic holding device facilitates the function that the device is disassembled there is provided one；Its major function of the miniature ultrasonic transducer units is in micro-fluidic core During the test of piece actual sample introduction, the ultrasonic wave launched using it reduce sample solution with its inner passage of the micro-fluidic chip 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 micro-fluidic chip its inner passage inner surface, and then check the substrate of the dimethyl silicone polymer material its body phase The effect of swallowing up to the large biological molecule；Softness simultaneously has its function of the substrate of the dimethyl silicone polymer material of elasticity including with it To the property of the strong absorption of ultrasonic wave, ultrasonic wave is absorbed strongly, and thereby in micro-fluidic chip terminal to the sample introduction The rapid decrement of ultrasonic intensity is realized within limited short distance between end；And, Micropump, the Micropump connects with the sample introduction end Connect；The function of the Micropump is that the interfacial tension between the inwall of the sample solution and its inner passage of micro-fluidic chip is by this Ul-trasonic irradiation and reduce, under the increased precondition of alternate compatibility, come and the ultrasound with the mechanicalness pumping strength of the Micropump Interfacial tension difference its driving force brought between the two ends of ripple induction is supported mutually, adjusts mutually, is mutually coupled, The strength that one driving test liquid flows to the terminal direction flowing is pooled in the way of Collaboration；The cover plate and substrate its Thickness is between 1.0 millimeters and 5.0 millimeters；And, ultrasonic wave damper, its profile of the ultrasonic wave damper in it is block, Tabular is bar-shaped；Its material of the ultrasonic wave damper is microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, bullet Power is pressed from both sides, and 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, wherein one The medial surface of individual 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 the ultrasonic wave and disappeared Subtract device, 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 be clipped in one Rise, the strong consumption to ultrasonic wave that the ultrasonic wave damper is brought with its material, further support in the micro-fluidic core The piece terminal thereby further expands to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end Difference between its interfacial tension of big described its interfacial tension of sample introduction end and the terminal.

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 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 eight channel microfluidic chip, Eight kinds of classifiable tumor mark diagnostic antigens are detected respectively using eight passage electrochemical analytical instruments.

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 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, the difference of the interfacial tension between the two ends can cause a kind of driving force, and this kind is poor because of interfacial tension Its function of driving force is to drive test liquid stream in strong hydrophobic capillary channel originally to the terminal side caused by different To flowing；And the simultaneous Micropump in structure, its function is, leads in the sample solution and the micro-fluidic chip inside it Interfacial tension between the inwall in road is reduced by the ul-trasonic irradiation, under the increased precondition of alternate compatibility, with the Micropump The two ends that are induced come the ultrasonic wave of mechanicalness pumping strength between interfacial tension difference its driving force for being brought Support mutually, adjust mutually, be mutually coupled, one driving test liquid is pooled in the way of Collaboration and flows to the terminal side To the strength of flowing；The presence of the Micropump so that its ultrasonic wave emissive porwer of the miniature ultrasonic transducer units can be allowed to appropriateness Reduction, this is particularly suitable for for the situation containing ultrasonic wave sensitive composition in detection object；And due to the ultrasonic transducer and its The presence of radiated ultrasonic wave, it is possible to increase alternate compatibility, reduce interfacial tension, and provide the two ends interfacial tension difference its The special driving force brought, then, in this case, its flow resistance in the micro-channel of test liquid stream significantly drops Low, correspondingly, its running resistance of the Micropump is greatly reduced, so, and the Micropump just can be to carry out than relatively low pumping pressure For the pumping work of the sample solution, because mechanical pumping pressure is greatly reduced, therefore, in such a situation, Just be not susceptible to because sample introduction terminal tool pumping pressure it is excessive caused by the sample introduction end and its near zone the micro-channel drum Between bubble, expansion, deformation, distortion and the region substrate and cover plate the problems such as stripping etc.；This case dual drive coupling running Scheme and add for the sample fluid flow act it is handling, can allow for using ultrasonic intensity, ultrasonic frequency, Micropump pump power, Micropump pumping pressure etc. multiple indexs include flowing forward to be directed to the flow rate of the flowing, flowing action Dynamic or pause flowing or acceleration flowing etc. flowing action carries out multi-parameter and accurately manipulated；By this case dual drive coupling running Scheme, entirely without must the substrate of the dimethyl silicone polymer material its micro-channel etc. relevant surfaces be carried out with any surface chemistry Modification or surface chemical modification, have altogether dispensed with the laborious procedures of the surface chemical modification or surface chemical modification；On the other hand, The ultrasonic wave of the low-power, high-frequency band, additionally it is possible to contain the large biological molecule in sample in the literalness naked poly dimethyl Absorption on its inner surface of pipeline of siloxanes substrate, and then contain its body phase of dimethyl silicone polymer substrate to described biological big point The effect of swallowing up of son；The Reversible binding thing of the antigen, antibody and antigen and antibody is all to belong to big point described of biology certainly The type of son；Because described suction-operated and the described effect of swallowing up effectively are contained, therefore, dependence test result will It is better able to objectively reflect actual conditions；The effect of the low-power, high-frequency band ultrasonic wave, certainly also include facilitate antigen, The quick of Reversible binding reaction between antibody is reached, 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.

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 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.

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, should The component that part can freely depart from is reused many times in which just can circulate benignly；The architectural feature is conducive to saving 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；The components such as infusion tube and Micropump are depicted without in Fig. 2.

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, and 23 be infusion tube, and 24 be Micropump；Figure The chain ring type magnetic holding device structure in example is only the legend structure of signal, and the actual chain ring type magnetic holding device structure is not limited to the figure Example chain ring type magnetic holding device structure；Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends Difference driving, the flow direction of its test liquid stream.

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 and Fig. 2 are shown embodiment, its main points of the example are that the structure of the device includes micro-fluidic core Piece, the structure of the micro-fluidic chip includes the substrate 4 and cover plate 5 of installing bonded to each other together, the substrate 4 and cover plate 5 It is plate object or tablet, that face towards the cover plate 5 of the substrate 4 is contained to be formed via mould pressing process or etching technics Channel structure, substrate 4 bonded to each other being installed together and the cover plate 5 have been built into the miniflow containing pipeline configuration jointly Chip is controlled, the locations of structures of the pipeline is located at the substrate 4 and the cover plate 5 juncture area bonded to each other, the two ends point of the pipeline It is not connected with the sample introduction end 3 of the micro-fluidic chip and terminal 2, the sample introduction end 3 is the injection of the micro-fluidic chip sample solution End, the terminal 2 is the terminal of sample solution flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, and the terminal 2 is with being somebody's turn to do Sample introduction end 3 is located remotely from each other, and the distance between the terminal 2 and the sample introduction end 3 are between 3 centimetres and 10 centimetres, in the pipe In road on diverse location in order or backward is equiped with working electrode and to electrode and reference electrode, the order refers to institute Its locations of structures of reference electrode is stated closer to the position of terminal 2, the backward refers to that the reference electrode locations of structures is more leaned on The nearly position of sample introduction end 3, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded tumour The gold size sensitive membrane of mark antibody is constituted, and parallel construction is presented in the construction of the pipeline, and the pipeline in parallel construction is by eight Lateral parallel connection is constituted, and its appearance profile of the pipeline of the presentation parallel construction is similar to the profile of parallel circuit, described The quantity of working electrode is eight, and the installation position of eight working electrodes is located in eight laterals respectively, and, Tumor markers antibody in the sensitive membrane structure of its top layer gold size of eight working electrodes is respectively can be special to tumor markers antigen The opposite sex combine eight kinds of tumor markers antibody materials, eight kinds of antibody materials be respectively tumor markers antibody CA199, CA153, CA125, CA242, AFP, CEA, EB and β-HCG, the antigen are the antigen of broad sense, and the antibody is the antibody of broad sense, Its material of the working electrode is argent material, gold material, carbon material or thermal decomposition conducting polymer material, the work Make electrode its pattern and column, sheet or thread is presented, its material of the substrate 4 is dimethyl silicone polymer material, the substrate 4 Its surface is the surface of primary form, the surface of the primary form its be intended to refer to not by any surface chemical modification or appoint The surface of the primary form of the material of what surface chemical modification, the structure of the device also includes chain ring type magnetic holding device 1, the chain Have six links 8,11,13,15,18,20 in its structure of ring type magnetic holding device 1, the link 8,11,13, 15th, 18,20 in strip, shaft-like or bar-shaped, and each adjacent link is hinged to form chain link, and its appearance profile of the chain link is in Hexagonal annular structure, its locations of structures of each drift angle 10,12,14,17,19,21 of the hexagonal annular structure is Articulated structure position, in the link 8,15 of opposite side position, its material is magnetic conductivity material to two therein of the hexagonal annular structure Matter, its material of the remaining four processes 11,13,18,20 of the hexagonal annular structure is non-magnetic material, the non-magnetic Property material refers to a link among the material not responded strongly to externally-applied magnetic field, two links of the magnetic conductivity material Magnet exciting coil 16 is wound with 15, this is wound with both sides neighbour position of the link 15 in its magnet exciting coil 16 of magnet exciting coil 16 The pole shoe for being respectively equiped with a magnetic conductivity material is put, two pole shoes 9,22 are had, two pole shoes 9,22 are directed to Attach to fix on the link 8 of another magnetic conductivity material, its surface of the link 8 of another magnetic conductivity material and be equiped with miniature surpass Acoustic wave transducer 6, relies on the chain ring type magnetic holding device 1 socket of electromagnetism adhesive strength to be positioned at its described end of the micro-fluidic chip The close position at end 2, and, higher-order of oscillation electric signal transmission cable 7, one end of the higher-order of oscillation electric signal transmission cable 7 Linked together with the miniature ultrasonic transducer units 6；The chain ring type magnetic holding device 1 facilitates the work(that the device is disassembled there is provided one Energy；Its major function of the miniature ultrasonic transducer units 6 is that, in the actual sample introduction test of micro-fluidic chip, utilize that it is launched is super Sound wave reduces the interfacial tension between sample solution and the inwall of its inner passage of micro-fluidic chip, can be compatible, and And, using the distance between the sample introduction end 3 and the terminal 2 and the installation position of miniature ultrasonic transducer units 6 difference with And its difference on the ultrasonic intensity experienced, its interfacial tension of sample introduction end 3 described in induced synthesis and described its boundary of terminal 2 Interfacial tension difference between difference between the tension force of face, the micro-fluidic chip two ends 2,3 being somebody's turn to do in the micro-fluidic chip Pressure gap is formed between two ends 2,3, the pressure gap can drive sample solution to be flowed to the direction of terminal 2；This is miniature Ultrasonic transducer 6 its function also include with its ultrasonic wave launched check large biological molecule contained in sample its at this Absorption on its inner passage inner surface of micro-fluidic chip, and then check the substrate 4 of the dimethyl silicone polymer material its body phase pair The effect of swallowing up of the large biological molecule；Softness simultaneously has its function of the substrate 4 of the dimethyl silicone polymer material of elasticity including with it To the property of the strong absorption of ultrasonic wave, ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic chip, the terminal 2 is entered to this The rapid decrement of ultrasonic intensity is realized within limited short distance between sample end 3；And, Micropump 24, the Micropump 24 with The sample introduction end 3 is connected；The function of the Micropump 24 is, the sample solution Yu its inner passage of micro-fluidic chip inwall it Between interfacial tension reduced by the ul-trasonic irradiation, under the increased precondition of alternate compatibility, with the machinery of the Micropump 24 Property the two ends 2,3 that are induced come the ultrasonic wave of pumping strength between interfacial tension difference its driving force for being brought it is mutual Mutually support, adjust mutually, be mutually coupled, one driving test liquid is pooled in the way of Collaboration and flows to the side of terminal 2 To the strength of flowing；Its thickness of the cover plate 5 and substrate 4 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 be microcellular rubber, Sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, the inner side of each clamping limb Face is relative with the medial surface of another clamping limb, and the medial surface of one of clamping limb is close to the sample introduction end 3 of the micro-fluidic chip, The medial surface of another clamping limb is close to the ultrasonic wave damper, the elastic clip entering the micro-fluidic chip with its gripping strength Sample end 3 and the ultrasonic wave damper are clipped together bonded to each otherly, the ultrasonic wave damper with its material brought to ultrasonic wave Strong consumption, further support the limited short distance arrived between the sample introduction end 3 in the micro-fluidic chip terminal 2 it The rapid decrement of ultrasonic intensity is inside realized, and thereby further expands described its interfacial tension of sample introduction end 3 and the terminal 2 Difference between 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 2,3 pressure differentials drive, its try The flow direction of sample liquid stream.

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

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

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

The Micropump 24 can be customized to specialized factory.

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

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

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

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

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

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. a kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes, it is characterised in that the structure of the device Including micro-fluidic chip, the structure of the micro-fluidic chip includes the substrate and cover plate of installing bonded to each other together, the substrate and Cover plate is plate object or tablet, and that face towards the cover plate of the substrate is contained to be formed via mould pressing process or etching technics Channel structure, substrate bonded to each other being installed together and the cover plate have been built into the micro-fluidic core containing pipeline configuration jointly 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 eight 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 eight, this eight The installation position of working electrode is located in eight laterals respectively, and, its top layer gold size of eight working electrodes is sensitive Tumor markers antibody in membrane structure is the eight kinds of tumor markers antibody that can be specifically bound to tumor markers antigen respectively Material, eight kinds of antibody materials are tumor markers antibody CA199, CA153, CA125, CA242, AFP, CEA, EB respectively And β-HCG, 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 metal Column, piece is presented in silver-colored material, gold material, carbon material or thermal decomposition conducting polymer material, its pattern of the working electrode Shape is thread, and its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, and this is primary The surface of form its be intended to refer to the primary of the material not no by any surface chemical modification or any surface chemical modification The surface of form, the structure of the device also includes chain ring type magnetic holding device, and six rings are had in its structure of the chain ring type magnetic holding device Section, the link is in strip, shaft-like or bar-shaped, and each adjacent link is hinged to form chain link, and its appearance profile of the chain link is in Hexagonal annular structure, its locations of structures of each drift angle of the hexagonal annular structure is articulated structure position, the hexagonal rings In the link of opposite side position, its material is magnetic conductivity material, the remainder of the hexagonal annular structure four to two therein of shape structure Its material of link is non-magnetic material, and the non magnetic material refers to the material not responded strongly to externally-applied magnetic field, and this is led Magnet exciting coil is wound with a link among two links of magnetic material, this is wound with the link of magnet exciting coil in its excitation The pole shoe of a magnetic conductivity material is respectively equiped with the both sides neighbor positions of coil, two pole shoes are had, two pole shoes are equal The link of another magnetic conductivity material is pointed to, attaching is fixed on its surface of the link of another magnetic conductivity material is equiped with miniature surpass Acoustic wave transducer, relies on the chain ring type magnetic holding device socket of electromagnetism adhesive strength to be positioned at the micro-fluidic chip its terminal Close position, and, higher-order of oscillation electric signal transmission cable, one end of the higher-order of oscillation electric signal transmission cable is miniature super with this Acoustic wave transducer links together；The chain ring type magnetic holding device facilitates the function that the device is disassembled there is provided one；The miniature ultrasonic Its major function of wave transducer is that the ultrasonic wave launched using it is molten to reduce sample in the actual sample introduction test of micro-fluidic chip Interfacial tension between liquid and the inwall of its inner passage of micro-fluidic chip, can be compatible, also, utilizes the sample introduction The distance between end and the terminal and the miniature ultrasonic transducer units installation position difference and its ultrasonic wave experienced Difference between difference in intensity, its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension, the miniflow Interfacial tension difference between the control chip two ends can form pressure gap between the two ends of the micro-fluidic chip, the pressure differential It is different to drive sample solution to the end flow；Its function of the miniature ultrasonic transducer units also includes the ultrasonic wave launched with it Check in sample contained large biological molecule its absorption on the micro-fluidic chip its inner passage inner surface, and then check this Swallow up effect of its body phase of the substrate of dimethyl silicone polymer material to the large biological molecule；The poly dimethyl that is soft and having elasticity The substrate of siloxanes material its function includes, with its property to the strong absorption of ultrasonic wave, ultrasonic wave being absorbed strongly, and by This realizes the rapid decrement of ultrasonic intensity within micro-fluidic chip terminal to the limited short distance between the sample introduction end； And, Micropump, the Micropump is connected with the sample introduction end；The function of the Micropump is, in the sample solution and the micro-fluidic chip in it Interfacial tension between the inwall of portion's passage is reduced by the ul-trasonic irradiation, under the increased precondition of alternate compatibility, with this Its driving that is brought of interfacial tension difference between the two ends that are induced come the ultrasonic wave of mechanicalness pumping strength of Micropump Strength is supported mutually, adjusts mutually, is mutually coupled, and one driving test liquid is pooled in the way of Collaboration and flows to the end The strength of extreme direction flowing；Described its thickness of cover plate and substrate 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 be microcellular rubber, Sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, the inner side of each clamping limb Face is relative with the medial surface of another clamping limb, and the medial surface of one of clamping limb is 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 entering the micro-fluidic chip with its gripping strength Sample end and the ultrasonic wave damper are clipped together bonded to each otherly, the ultrasonic wave damper with its material brought to ultrasonic wave Strong consumption, further supports to realize within micro-fluidic chip terminal to the limited short distance between the sample introduction end The rapid decrement of ultrasonic intensity, and thereby further expand described its interfacial tension of sample introduction end and the terminal its interfacial tension it Between difference.

2. a kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes according to claim 1, it is special Levy and be, it is capillary channel that the pipeline, which includes the lateral,.

3. a kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes according to claim 1, it is special Levy and be, the thermal decomposition conducting polymer be by polyimides or polyacrylonitrile be heat-treated through anoxybiotic after the electric conductivity material that is formed Material.

4. a kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes according to claim 1, it is special Levy and be, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the working electrode Length between 1 micron to 15000 microns.

5. a kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes according to claim 1, it is special Levy and be, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.

6. a kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes according to claim 1, it is special Levy and be, its material of the cover plate in structure is dimethyl silicone polymer material.

7. a kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes according to claim 1, it is special Levy and be, the Micropump is miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.

8. a kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes according to claim 1, it is special Levy and be, the microcellular rubber is micropore silicon rubber or micropore fluorubber.

9. a kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes according to claim 1, it is special Levy and 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 other end is connected with the higher-order of oscillation electric signal generator.

10. a kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes according to claim 1, 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.