CN107413400A - The classifiable tumor markers in detecting micro flow control chip device that women is applicable - Google Patents

Abstract

The present invention relates to the classifiable tumor markers in detecting micro flow control chip device that a kind of women is applicable, belong to analysis testing field.The substrate for the classifiable tumor markers in detecting micro-fluidic chip that women is applicable is made, it is necessary to solve a series of problems so that PDMS is dimethyl silicone polymer.This case main points are, the selected PDMS with ecosystem surface of substrate, and its neighbor positions attaches installing miniature ultrasonic transducer units in the sample liquid stream terminal of the micro-fluidic chip, sample liquid stream is induced to be flowed from its sample introduction end of the chip along its pipeline of the chip to the terminal direction with ultrasonic wave, micron silica granule filler is filled up in its pipeline of the chip, its function of the filler includes supporting pipeline inwall, and, with the set of hydrophily fluid channel come the hydrophobic pipeline of compensatory script, and, extruding, cover inner-walls of duct face and thereby reduce the chance that large biological molecule contacts with the internal face.

Description

The classifiable tumor markers in detecting micro flow control chip device that women is applicable

Technical field

The present invention relates to the classifiable tumor markers in detecting micro flow control chip device that a kind of women is applicable, belong to point Analyse testing field.

Background technology

Tumor markers (tumor marker, TM) refers in the generation and breeding of tumour, by tumour cell sheet Either tumour cell is reacted and caused, a kind of material of the presence of reflection tumour and growth by body caused by body, bag Include protein, hormone, enzyme (isodynamic enzyme) and oncoprotein etc..The tumor markers in blood samples of patients or body fluid is chemically examined, can be Early detection tumour in cancer screening, and the effect of observe oncotherapy and judge patient's prognosis.Clinically commonly use at present Tumor markers has：(1) alpha-fetoprotein (AFP) is the mark of the tumours such as primary carcinoma of liver, carcinoma of testis, oophoroma；(2) cancer embryo Antigen (CEA) is the mark of the tumours such as digestive system tumor, lung cancer, breast cancer；(3) CA125 (CA125) is ovary The mark of the tumours such as cancer；(4) CA153 (CA153) is the mark of the tumours such as breast cancer；(5) CA19-9 (CA19-9) it is the mark of digestive system tumor；(6) CA724 (CA724) is the mark of the tumours such as stomach cancer, oophoroma Thing；(7) carbohydrate antigen 242 (CA242) is the mark of digestive system tumor；(8) CA50 (CA50) is digestive system The mark of the tumours such as tumour, breast cancer, lung cancer；(9) CYFRA21-1 (Cy211) is the mark of the tumours such as non-small cell lung cancer； (10) neuronspecific enolase (NSE) is the mark of the tumours such as ED-SCLC, neuroendocrine tumor；(11) before Row gland specific antigen (PSA) is the tumor markers of prostate cancer；(12) human chorionic gonadotrophin (HCG) is that embryo is thin The mark of the tumours such as born of the same parents' cancer, trophoblastic tumor (suede cancer, vesicular mole)；(13) thyroglobulin (TG) is the mark of thyroid cancer Will thing；(14) ferritin (SF) is the mark of the tumours such as digestive system tumor, liver cancer, breast cancer, lung cancer；(15) β 2- microballoons Albumen (β 2-MG) is in patient body fluids such as chronic lymphocytic leukemia, lymthoma, myeloma, lung cancer, thyroid cancer, nasopharyngeal carcinoma Middle rise；(16) squamous cell antigen (SCC) is the tumor markerses such as cervical carcinoma, lung squamous cancer, the cancer of the esophagus.Clinically detect at present The tumor markers overwhelming majority be not only present in malignant tumour, exist in benign tumour, even embryonic tissue, normal group In knitting.Therefore, tumor markers has dynamic chek and multinomial joint inspection more valuable.So for numerous tumor-markers Thing, clinically how to selectDifferent tumours understands some relatively special tumor markerses, as CA153 often appears in mammary gland Cancer；CEA often appears in intestinal cancer, stomach cancer；CA19-9 often appears in intestinal cancer, cancer of pancreas；CA125 often appears in oophoroma etc..Face Bed doctor can be according to the different mark of different tumor examinations.Same tumour or different types of tumour can have a kind of or several Kind tumor markers is abnormal；Same tumor markers can occur in different tumours.To improve the auxiliary of tumor markers Which kind of mark can carry out tumor markers joint-detection to diagnostic value as the follow-up visit monitoring index after treatment with determination, The complementary tumor markers composition best of breed of several sensitivity of reasonable selection, specific performance, carries out joint-detection.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, can be with Referring to following Chinese invention patent application case：CN200410041175.3、CN200510026780.8、 CN200610040051.2、CN200910064647.X。

Only for the microfluidic chip technology overall general picture of itself, it is first to may refer to famous micro-fluidic expert Lin Ping Cheng The raw monograph " diagram Microfluid based Lab on a chip " gone out not long ago, the monograph is published via Science Press, the monograph for Past of microflow control technique, now, and, vision of the future etc. etc., suffer from detail, be deep into the treatise of detail Discuss.

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 conduit and the cover plate to fit together therewith, institute State the fluid course on substrate, before upper cover plate is assembled, it is apparent on see to be exactly some conduits, wait until lid is covered thereon After piece, just really closure forms the fluid course, and the conduit inner surface of the conduit is together with the part that surround the conduit Cover plate forms described fluid course together；So, it is clear that assemble the fluid course after completing, its inner surface face Long-pending major part is the inner surface area of that conduit, and in other words, the state or property of the conduit inner surface are substantially determined The integrality or property of the fluid course are determined；Therefore say, the inner surface state or interior of this conduit of the structure on substrate Surface nature is key factor；In principle, any material that can be kept or keep its solid forms substantially, can be used To make substrate and cover plate, such as, the material that can act as substrate and cover plate can be monocrystalline silicon piece, quartz plate, sheet glass, height Polymers such as dimethyl silicone polymer, polymethyl methacrylate, makrolon etc.；Certainly, the selection of substrate and the choosing of cover plate Material be able to can also be differed with identical；From the point of view of material consumption, manufacture difficulty and application popularization prospect etc. etc., these Not small difference, the especially selection of that substrate between material be present, have a great influence.

In various substrate making materials, dimethyl silicone polymer, i.e. PDMS, comparatively very easily shaping, at this It is extremely simple that conduit is made on the substrate of sample, and the lower cost for material, substrate is made with the polydimethyl siloxane material, Conduit 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, and making is 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 alphabetical PDMS is referred to of abridging, itself are a kind of strong Strong hydrophobic material, conduit is built on this material, if without being operated for the modified of the conduit surface, then, it is whole After body assembling is completed, that is, after covering cover plate, because the conduit its inner surface in structure occupies most fluid course Inner surface, then, its strong hydrophobic property of the PDMS conduits inner surface, is deciding factor, it can be similar to water The fine liquid stream of polar liquid of solution by becoming very difficult, its flow resistance is big, or even in general Micropump is all difficult to Promote, certainly, if cover plate also selects to use the PDMS material, then, problem is substantially identical, similar；Therefore, existing Among having technology, modification is modified particular for the conduit inner surface on the PDMS material, is necessary operation；So, this The individual modified operation for PDMS conduit inner surfaces is pretty troublesomeThat falls nor this problem, forms serious technical puzzlement, It is another problem：PDMS polymer molecules inside its body phase of this PDMS material substrate have to be diffused to the surface, moves automatically The characteristic of shifting, the characteristic that this substrate body phase inside PDMS polymer molecules are diffused to the surface, migrated automatically, will cause by table State after the modification of its inner surface of that conduit of face modifying and decorating can not maintain the sufficiently long time, and that is through surface Holding time for conduit its inner surface state after modification is substantially only sufficient to the time needs for completing laboratory internal test experiments； In other words, by surface is modified or the PDMS conduit inner surfaces of surface modification, after it is modified or institute's shape after modification is said Into surface state can not be lasting, but soon automatically tend to or say become again surface be modified before surface state, compared with The strong hydrophobic surface state of that script is returned in the short time, then, just think, such micro-fluidic chip can be big Amount making, mass storage, it is widely popularized, answer is it is obvious that is, impossible.Conduit on this PDMS material, does not do If surface modification, it can not pump and pass through similar to the fine liquid stream of polar solvent of the aqueous solution, chip also cannot just use；And such as Fruit has been cooked surface modification, can not persistently keep its state after modifying again, or equally can not popularization and application.

According to the literature, there is a kind of expedient solution, be that a small amount of surface-active is added in sample to be tested solution Agent, so as to which during test, dynamic, temporary transient effective surface hydrophilic layer is built temporarily in the PDMS conduits inner surface； However, due to the amphipathic characteristic of surfactant, the introduced surfactant of the program is inevitable simultaneously also can be with sample solution In tested composition occur combination so that tested composition can not be detected normally or it is detected ratio and dubiously dropped It is low；The surfactant is possibly even fully wrapped around by tested composition with micelle form so that tested composition can not be detected or Identification；Therefore, this kind adds the scheme of surfactant into sample solution, is far from a preferable solution.

So, how to accomplish that substrate can either be made using cheap PDMS material, and the conduit can be released Inner surface decorating state can not persistently, chip can not largely make, largely lay in and then be widely popularized and such a make this area The puzzlement that numerous professionals 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, it is stated that, its surface is strongly hydrophobic above, this strong hydrophobic Material surface and also have 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 it is gradually deep, until It is heavy to be trapped within the body phase of PDMS substrates, in fact, this process, partly it is also due to PDMS material body phase interior polymer Molecule, which has, to be diffused to the surface, caused by travel motion；Such case, it can also be explained from another angle, i.e. continue not Disconnectedly from inside PDMS body phases to those polymer molecules of its diffusion into the surface, migration, its result moved, be little by little by that It has been involved in a bit by the large biological molecule of adsorption within the body phase of PDMS substrates, briefly, these adsorbed biologies Macromolecular is exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up the phenomenon of large biological molecule, its institute Caused by influence, necessarily cause the severe deviations of all kinds of test data of experiment for being related to large biological molecule.

As described above, the problem of PDMS substrates, is, its not only adsorption large biological molecule, and swallow up biological big point Son, so, as the large biological molecule of experiment test object, its disappearance will not stop because surface saturation is adsorbed, and It is, it is constantly adsorbed, also constantly swallowed up.

On PDMS substrates, its body phase is constantly swallowed up and tests showing for associated biomolecule macromolecular in related experiment test process As, it is to say that another kind, which is explained, substantial amounts of Minute pores in PDMS body phases be present, associated biomolecule macromolecular by after adsorption, Depression enters these Minute pores, and then is swallowed up；However, inventor thinks, those can allow the sky of miniature scale Qi leel squeezes into the Minute pores therebetween, not equal to saying that they also can directly allow the large biological molecule of relative large scale to enter Enter, both difference on yardstick are huge, must not make sweeping generalizations.Explanation is bypassed, in any case, as dependence test analysis object Large biological molecule is adsorbed by PDMS substrate conduits inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is known objective Existing phenomenon.

, can be from containment PDMS surfaces pair in order to prevent swallow up effect of this PDMS substrate bodies relative to large biological molecule The absorption of large biological molecule addresses, 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 channel portion, by chemistry The conduit inner surface of modification, can contain its absorption to large biological molecule, 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 is modified it Surface state afterwards can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface, migrate automatically Process, can soon by that by surface chemical modification be modified conduit inner surface state become again script it is strong it is hydrophobic simultaneously 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 substrates its Conduit inner surface 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, and can is enough Reach and contain the absorption process of the PDMS substrate conduit inner surfaces to large biological molecule for a long time, and then prevent PDMS substrate bodies relative The effect of swallowing up of 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 equally makes this area numerous specially as another problem addressed above Industry 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.Should Also be present many year in problem, so far, also not yet properly settled.

Third, the polydimethyl siloxane material, namely PDMS material, the active force very little wherein between polymer molecule, The polymer molecule of low polymerization degree inside its body phase is in constantly into the dynamic process of surface migration, therefore, includes PDMS After it has been formed, the surface topography in its inner-walls of duct face of chip can be because of described low polymerization degree polymer point for the chip of substrate material Son moves about, pours into the surface and change, and the change of its pattern is somewhat similarly to Rheological Deformation, trickling deformation or creep and become Pattern caused by shape institute is possible changes；In the higher PDMS material of some low polymerization degree component ratios, this kind somewhat similar Can be showed in the phenomenon of Rheological Deformation, trickling deformation or the deformation of creep must be than more significant；This kind include PDMS substrates chip its The dynamic of inner-walls of duct surface topography after shaping changes property, namely the described property or stream that are somewhat similarly to Rheological Deformation Dropping down the property of deformation or the property of the deformation of creep, the word of rheology one is applied mechanically in this case, integration, also referred to as the rheological equationm of state or rheology become Shape property, the dynamic of corresponding inner-walls of duct face pattern change, and this case is also referred to as rheology；As described above, because of this kind of material Expect certain Rheological Deformation property as described above that its own has, its manufactured goods actually can at leisure Rheological Deformation and cause The manufactured goods total form generation changes；Influence caused by its Rheological Deformation property, it is to be not easy to feel in terms of macroscopic perspective Examine, still, for the very fine micro-fluidic chip of its internal structure, the rheological equationm of state can but cause bigger shadow Ring, the fluid course namely the pipeline therefore, during pre-production formed, because the wall of its tube chamber of pipeline is main It is the wall of PDMS materials, so, the cross-sectional area of the pipeline actually can gradually become because of rheology over time It is small, stated differently, since the reason for the rheology, the natively finer pipeline that is flowed through for liquid sample Its tube chamber the more can become the more narrow, in the case of flow time is sufficiently long, or even the pipeline tube chamber can partly close or all Ground closes, and then make it that sample fluid course is thoroughly blocked, and closes with being even also not reaching to its luminal part of pipeline The degree closed or fully closed, its fluid passage that can be provided of that pipeline narrow because of rheology, then, in pipeline Its inner surface originally be exactly strongly it is hydrophobic in the case of, aqueous sample liquid is just more difficult to by becoming more so because of rheology Narrow micro-channel, then, the influence of substrate rheology how is resisted, maintains the basic framework of the pipeline not occur seriously to become for a long time The problem of shape, also, keep the long-term unobstructed of the pipeline is exactly a urgent need to resolve.

The content of the invention

The technical problem to be solved by the invention is to provide a package solution, solves totally above A series of problems addressed, also, the solution is applied to a kind of new being directed to of structure and belongs to women physical examination spy Do not need to pay close attention to seven kinds carry out the micro-fluidic chip dress of examination simultaneously while detection than more typical primary tumor mark Put.

The present invention solves the technical problem by following scheme, and the device that the program provides is the allusion quotation that a kind of women is applicable Type tumor markers joint-detection micro flow control chip device, it is characterised in that the structure of the device includes multichannel micro-fluidic Chip, the structure of the micro-fluidic chip include being bonded to each other the substrate and cover plate of installing together, and the substrate and cover plate are The conduit via mould pressing process or etching technics formation is contained in plate object or tablet, that face towards the cover plate of the substrate Structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or simply The window structure that drilling technology is formed, it is bonded to each other the substrate being installed together and has been built into jointly with the cover plate and contain pipeline The micro-fluidic chip of structure and the liquid pool structure being attached thereto, the locations of structures of the pipeline is located at the substrate and the cover plate is mutual The interface zone of fitting, its side of the window is blocked by the cover plate and opposite side opens, and the locations of structures of the window is exactly described The locations of structures of liquid pool, the liquid pool have 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 have one or more sample introduction end liquid pool, the sample introduction End refers to the injection end position of detected solution during the micro-fluidic chip actual sample introduction, the micro-fluidic chip terminal location then There is a terminal liquid pool, the terminal refers to liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested Terminal location, the terminal are located remotely from each other with the sample introduction end, and one end of the pipeline joins with the sample introduction end liquid pool positioned at sample introduction end It is logical, the other end of the pipeline and the terminal liquid pool UNICOM of the terminal positioned at the micro-fluidic chip, and, sequentially or The working electrode that is respectively installed in backward in the pipeline on diverse location and electrode and reference electrode, the order are referred to Be its locations of structures of the reference electrode closer to the terminal location, the backward refers to the reference electrode structure bit Put closer to the sample introduction end position, the working electrode is by conductive electrode and the embedding being attached on the conductive electrode The gold size sensitive membrane of tumor markers antibody is formed, and parallel construction, the pipe in parallel construction is presented in the construction of the pipeline Road is made up of eight lateral parallel connections, and its appearance profile of the pipeline of the presentation parallel construction is similar to parallel circuit Profile, the quantity of the working electrode is eight, and the installation position of eight working electrodes is located at eight branched pipes respectively In road, and, the tumor markers antibody in its top layer gold size sensitivity membrane structure of eight working electrodes is to tumour mark respectively Eight kinds of tumor markers antibody materials that will thing antigen can be specifically bound, eight kinds of antibody materials are that tumor markers resists respectively Body 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 are argent material, gold material, carbon material or thermal decomposition conducting polymer Column, sheet or thread is presented in material, its pattern of the working electrode, and its material of the substrate is dimethyl silicone polymer material, Its surface of the substrate is the surface of primary form, the surface of the primary form its be intended to refer to and do not pass through any surface chemistry The surface of the primary form of the material of modification or any surface chemical modification, the structure of the device are also changed including miniature ultrasonic Energy device, and, higher-order of oscillation electric signal transmission cable, one end and the miniature ultrasonic of the higher-order of oscillation electric signal transmission cable Transducer links together, the miniature ultrasonic transducer units attach be installed in the micro-fluidic chip cover plate or substrate it is neighbouring The position of the terminal；Its major function of the miniature ultrasonic transducer units is in the actual sample introduction test of micro-fluidic chip, is utilized The distance between the sample introduction end and the terminal and miniature ultrasonic transducer units installation position difference and its experienced To ultrasonic intensity on difference, between its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension Difference, the interfacial tension difference between the micro-fluidic chip both ends can form pressure between the both ends of the micro-fluidic chip Difference, the pressure gap can drive sample solution to the end flow；The dimethyl silicone polymer material that is soft and having elasticity Its function of the substrate of matter also includes with its property to the strong absorption of ultrasonic wave, and ultrasonic wave is 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 many silica dioxide granules, many silica dioxide granules are filled in the pipeline, its tube chamber of the pipeline is by this Many silica dioxide granules are filled up, and its particle size range of the silica dioxide granule is between 10 microns and 200 microns, and this two Silicon oxide particle is that silica crystalline particles, silica glass granule or silica composition its shared percentage by weight exists More than 80% inorganic glass particles.

Its particle diameter of the silica dioxide granule can be that the basis between 10 microns and 200 microns is actually needed and any The particle diameter specified, such as 10 microns, 30 microns, 70 microns, 100 microns, 150 microns or 200 microns of the particle diameter, etc..

The scope of further preferred its particle diameter of the silica dioxide granule is between 100 microns and 200 microns.

Its pattern of the silica dioxide granule is unlimited, and the silica dioxide granule for example can be spheric granules, rod-shaped particles, length Cube shape particle or any amorphous granular.

The various silica dioxide granules manufacturing technology of itself is known technology.

Various forms, the silica dioxide granule market of all size are on sale.

The silica dioxide granule can also customize to specialized factory.

The preferred scope of its internal diameter of pipeline is between 500 microns and 1000 microns；It is but excellent compared to above-mentioned The internal diameter of the pipeline scope of choosing, more tiny internal diameter of the pipeline or thicker internal diameter of the pipeline are also what this case was allowed.

The tumor markers antibody is the antibody of broad sense, and the antibody of the broad sense refers to possessing antibody function or functionally Can occur to combine with tumor markers involved by various corresponding clinics and form immune complex or exempt from similar to antibody The material of the analog of epidemic disease compound；The tumor markers antigen is the antigen of broad sense, and the antigen of the broad sense refers to can Using corresponding antibodies or the material for being functionally similar to antibody need to differentiate, detect involved by the various clinics of enzyme mark detection Tumor markers.

The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and tumor markers antibody-solutions uniformly, is used a little Sample instrument point sample is coated on specified structure position, and forms its drying and forming-film.Tumor markers in the gold size sensitive membrane Antibody is the tumor markers antibody of horseradish peroxidase or glucose oxidase mark, and the gold size sensitive membrane has been wrapped Containing introducing complementary medium therein for the above-mentioned each tumor markers antibody of fixation, the complementary medium such as chitosan, Cellulose acetate, gelatin be 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 any Selected size, still, for using prepare liquid sample less as far as possible and reducing the consideration of reagent loss etc., the pipeline includes The passage of the preferred capillary level of lateral, the passage of the capillary level imply that its internal diameter and the capillary on ordinary meaning The suitable passage of the internal diameter of pipe.The shape of cross section of its inner passage of capillary can be arbitrary shape, described transversal Face shape is for example circular, oval, square, rectangle, bar shaped, naturally it is also possible to be the linear of bending, also, institute arbitrarily be present The interior shape of capillary is stated with the extension of pipeline, the shape of cross section of different parts can also allow to be different shapes. Only for the word of capillary 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, which may each be, appoints The selected shape of meaning, the arbitrarily selected shape such as column, sheet, strip or thread etc..It is described to electrode and institute The art-recognized meanings for stating the reference 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 capsule for transitional liquid storage Shape constructs, and its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, and the cavity shape is for example round Cylindrical cavity shape, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..

Only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field, It is known.

Various sizes, variously-shaped ultrasonic transducer are commercially available；Its size of commercially available miniature ultrasonic transducer units It may diminish 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 its It is known general technology for the professional in ultrasonic technology field for body.This case is not to this expansion superfluous words.

Only with regard to naked PDMS substrates itself conduit molding or lithographic technique for, be open-and-shut known technology； Similarly, 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 micro fluidic device can also include higher-order of oscillation electric signal generator；The higher-order of oscillation electric signal passes Its other end of transmission cable can be connected with the higher-order of oscillation electric signal generator.

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

The preferred scope of its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 2 milliwatts and 2000 milliwatts 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 certainly, and the annex is such as multiple tracks electrochemical workstation Deng the art-recognized meanings of the multiple tracks electrochemical workstation are known.The each work being related in this case microfluidic chip structure Electrode and to electrode and reference electrode etc., special it can get lines crossed and the multiple tracks electrochemical workstation via corresponding respectively The corresponding interface coupled.It is described that special to get lines crossed be for by each phase of each electrode and the multiple tracks electrochemical workstation Answer the private cable that interface is coupled to each other.The micro-fluidic chip in this case device, its structure can also include micro-valve, The quantity of the micro-valve is unlimited, and according to being actually needed, the micro-valve can be installed in any need in the microfluidic chip structure Position to be mounted；The word of micro-valve one is for the professional of micro fluidic chip technical field, the art-recognized meanings of itself It is known；The micro-valve itself manufacturing technology 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, still, It is recommending or say preferable its scope of the diameter between 0.1 micron to 2000 microns；The length of the working electrode can To allow to be that any setting is easily installed the length used, it is however recommended to or to say the preferable length its scope be 1 Micron is between 15000 microns.

It is installed in by spraying or point sample instrument point sample or the coating of other appropriate process described in the working electrode surface layer Gold size sensitive membrane, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness, It is however recommended to thickness preferable thickness is between 10 nanometers and 200 nanometers in other words.

The cover plate in chip structure, its material can allow to be any electrical insulating property material, such as：Polypropylene, Glass, polymethyl methacrylate, dimethyl silicone polymer, etc., in order to make smaller size of micro-fluidic chip, for example do Into the micro-fluidic chip of only 2.0 centimetres to 3.0 centimetres of super-small of length, and realized 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 Using dimethyl silicone polymer it is used as the cover plate, and this case technical scheme is allowed.

The preferred scope at 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 the thickness for being easy to assembling, the thickness of recommendation or say Preferable thickness is between 1.0 millimeters and 5.0 millimeters.Less thickness is advantageous to save material.

The application method of this case micro-fluidic chip：

Itd is proposed first based on this case and the first public new liquid stream driving principle, its application of this case micro-fluidic chip are transported Among work, the new liquid stream driving method is determined completely without involving any additional Micropump.

The interfacial tension difference that this case is formed between micro-fluidic chip both ends caused by the ultrasonic wave, Driving liquid stream flows in the capillary channel of eight channel microfluidic chip, right respectively using eight passage electrochemical analytical instruments Eight kinds of classifiable tumor mark diagnostic antigens are detected.

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 The tumor markers antibody of the corresponding horseradish peroxidase-labeled embedded by gold size sensitive membrane on electrode surface in each passage Capture.

2nd, the tumor markers antibody of horseradish peroxidase-labeled is formed with the tumor markers antigen in blood serum sample Immune complex.

3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, it is above-mentioned using amperometric detection Curent change caused by reaction, it 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 installs miniature ultrasonic with attaching in the terminal of the micro-fluidic chip Wave transducer, with the ultrasonic wave of miniature ultrasonic transducer units transmitting low-power, high-frequency band, meanwhile, utilize poly dimethyl silicon Its strong absorbability to ultrasonic wave of oxyalkyl piece, in shorter distance, it is, from the terminal to the sample introduction In the very short distance of only several centimeters yardsticks between end, reach the rapid decrement of ultrasonic intensity, thereby in the micro-fluidic core The difference of the interfacial tension is caused at the both ends of piece, and then, utilize its shape of the difference of the interfacial tension between the both ends Into the both ends between pressure gap, driving sample liquid stream in the pipeline to the terminal direction flow.By this case Liquid stream drive scheme, the equipment of traditional Micropump etc is altogether dispensed with；The micro-fluidic chip of Micropump is eliminated, it is tied Structure is more succinct, and its production process is less, and its cost of manufacture is lower, and this kind of succinct structure is more beneficial for reaching the low of micro-fluidic chip Cost application.

Its scheme of this case and by the pipeline except electrode installation take up space in addition to all clearance spaces whole Filled up with the silica dioxide granule.Those are filled in the silica dioxide granule in pipeline, and this case is to its overall abbreviation titanium dioxide Silicon grain filler, its function include support, withstand the tube chamber of the pipeline its inwall so that the tube chamber of the pipeline is from because of institute State rheology and narrow, prevent its reduced cross-sectional area of the tube chamber of the pipeline or even close, so as to maintain the base of the pipeline for a long time Serious deformation does not occur for this framework.

Numerous silica dioxide granule entities are mutually banked up under this case framework together at random in the pipeline, the titanium dioxide The function of silicon grain filler, also include certainly with the hydrophilic surface of its silica dioxide granule, utilize each adjacent titanium dioxide Mutual formed complications are continuous and its inner surface that is mutually close together by water-wetted surface of silicon grain has hydrophilic The space of property, in the hydrophilic fluid channel of the pipeline Inner Constitution network morphology, although this complications can be continuous All the time the fluid channel with hydrophilic nmature, then, inside the tube chamber of the pipeline simultaneously and a plurality of miniflow deposited The effect of its synthesis of road, integrated, cumulative superposition in other words, is the equal of the relatively fine hydrophilic capillary of caliber Passage；Its presence of the continuous hydrophilic fluid channel of the complications, the PDMS of the primary form is counteracted to a large extent The flow resistance for liquid sample caused by the strong hydrophobic property in its surface of substrate；In other words, because of liquid sample, it is accounted for The composition of maximum ratio is water, and liquid sample is substantially exactly the aqueous solution, therefore, the presence of the silica dioxide granule filler, Can significantly overcome with the unmodified PDMS substrates of hydrophobic property and surface its to the aqueous solution it is incompatible, repel and Barrier effect, so be greatly reduced belong to properties of Aqueous Solution sample liquid stream its be advanced through the resistance of pipeline.

Under this case framework, inside the tube chamber of the pipeline, the area of its lumen wall wall of former pipeline, because of described two The rigid of silicon oxide particle filler ties up, the table of part hydrophobic property that still can also be exposed on lumen wall wall Its area of face is already dramatically reduced, and the area on its still exposed part surface for belonging to hydrophobic property is much Less than the wall surface area of the hydrophobic property of the lumen wall wall in the presence of no silica dioxide granule filler； So, under this case framework, in its lumen of the pipeline, its remaining hydrophobic surface increases surface newly with hydrophilic part, and it is folded Adding, comprehensive, summation, cumulative technique effect, is to form the surface for tending to be hydrophilic on the whole；In other words, in institute State inside the tube chamber of pipeline, its interfacial tension between sample solution of the part surface of remaining hydrophobic property, plus parent The part of aqueous nature increases its interfacial tension between sample solution of surface newly, that it is superimposed, comprehensive, summation, cumulative Technique effect, be so that its solid-liquid interfacial tension inside the tube chamber of the pipeline synergy level off to capillary glass tube its Interfacial tension between tube chamber inner surface and sample solution.

Therefore, exist in the pipeline under this case framework for having stated silica dioxide granule filler, while rely on this Case sample liquid stream drive scheme, it becomes possible to the driving to sample liquid stream is reached with relatively low ultrasonic power, with this case mechanism The test liquid is driven to flow to the end flow.

On the other hand, due to its rheological equationms of state of the PDMS as substrate material, it is filled in the pipeline The interior silica dioxide granule filler, can gradually by constantly Rheological Deformation and to arest neighbors free space promote PDMS The pipeline wall of material more tightly wraps up, and this process eventually causes those part two for pressing close to the lumen wall wall Silicon oxide particle is stuck in original place or is stuck in original place or embedding in-situ silica dioxide granule and its embedded in original place, the part Incarceration is together, described due to this reason each other for the remaining silica dioxide granule banked up with being mutually closely packed together Silica dioxide granule filler just will not move in the pipeline easily, silica dioxide granule therein be also substantially all by Original place is locked in, therefore the stream framework of the micro-fluidic chip can be kept for a long time.

The particle size range of its particle of this case silica dioxide granule filler between 10 microns and 200 microns, compared to For general organic molecule, general large biological molecule, the particle diameter of its particle of this case silica dioxide granule filler can be rated as huge Greatly, due to its huge particle diameter, and the inner surface of the surface of its polarity and the pipeline of strong hydrophobic PDMS materials can not Mutually perhaps say and mutually melt, then, the huge silica dioxide granule of this kind of particle diameter can not be by the pipeline of PDMS materials Surface is adsorbed, and can not more be swallowed up by the inner surface of the pipeline of PDMS materials, the huge titanium dioxide of this kind of particle diameter Silicon grain surely not be fully sunk in easily or sink to completely PDMS materials its among intrinsic many Minute pores, and Because above it is stated that the rheology the reason for, the silica dioxide granule filler can be stuck in original place in other words it is embedding In original place without moving easily.

Inside the tube chamber of the pipeline, its lumen wall wall of former pipeline is entirely the surface of hydrophobic property originally, such as Upper described, under this case framework, rigid because of the silica dioxide granule filler ties up, on lumen wall wall still also Its area of the surface of part hydrophobic property that can be exposed is already dramatically reduced, and it is still exposed to belong to hydrophobicity The area on the part surface of matter has been far smaller than the tube chamber in the presence of no silica dioxide granule filler The wall surface area of the hydrophobic property of inwall wall；The reason for because of the rheology, it is close to those dioxies of lumen wall wall Silicon carbide particle, little by little it is partially embedded into or is partly absorbed among the lumen wall wall, the dioxy among the state Silicon carbide particle its towards the part surface of lumen wall wall with have occurred and that matching deformation the lumen wall wall it is tight Closely connected conjunction, then, the matching is deformed and closely pasted with silica particles having occurred and that in lumen wall wall The part wall of conjunction actually can not contact with flowing through the sample solution of pipeline, that is to say, that the wall of this part is Through suction-operated can not be produced to the large biological molecule therein that flows through the sample solution of pipeline and organic molecule.Based on above-mentioned Mechanism, then because fill up the pipeline the silica dioxide granule filler its presence, its lumen wall wall of the pipeline The overwhelming majority in face is tightly covered, and these described walls tightly covered can not be with flowing through the pipeline Sample solution contact, only remaining fraction be not brought into close contact by its surface of silica dioxide granule, tightly cover Hydrophobic surface may be contacted with sample solution, in other words, under this case framework, large biological molecule in sample solution and have Its direct touch opportunity with hydrophobic PDMS walls of machine molecule is significantly reduced, thus, the lumen wall faces of PDMS materials its The adsorptive hindrance and interference of swallowing up of large biological molecule and organic molecule are greatly reduced；As described above, this case scheme Be advantageous to exclude or weaken the adsorptive hindrance and swallow up interference, be advantageous to be lifted the reliability of correlation analysis test data.

As described above, this case silica dioxide granule filler, its function actually includes being similar to being directed to PDMS materials Inner surface of pipeline carry out chemical modification effect, functioning as its this respect of this case is by the pipeline of the PDMS materials Surface by the surface modification of hydrophobic property into the surface of hydrophilic nmature, still, with general, usual PDMS surface chemical modifications Its hydrophilic chemical decorative layer retention time is short, hydrophilic effect can not keep situation prolonged enough different, particle described in this case Huge silica dioxide granule filler, its particle being stuck by rheology can not both be moved easily, its huge particle diameter Particle can not more be swallowed up easily by the inner-walls of duct of PDMS materials, and therefore, its from this respect is similar to surface chemical modification Technique effect on see, its technique effect of this case, be form it is permanent, can not erase, can not consume, not be corroded, not by Hydrophilic surface reforming layer swallowing up, being not dissolved, it is just comparable to one kind in its correlation table of PDMS base materials in effect The permanent hydrophilic modifying superficial layer built on face.

It is related that the technical scheme of this case has dissolved its application to dimethyl silicone polymer substrate addressed above totally A series of technical barriers.Based on this case scheme, the very cheap polydimethyl siloxane material of this kind is just possible to micro- at this It is prepared by fluidic chip, production, using etc. field play bigger effect.

Its highly integrated structure of this case micro-fluidic chip, determine it among test is applied to the need of Serum samples Measure it is smaller, this advantageously reduce subject body and mind damage.

Brief description of the drawings

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

In figure, 1 is the substrate of dimethyl silicone polymer material, and 2 be cover plate, and 3 be higher-order of oscillation electric signal transmission cable, 4 It is miniature ultrasonic transducer units, 5 be the sample introduction end of the micro-fluidic chip, and 6 be the terminal of the micro-fluidic chip；Legend In arrow indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, the flowing of its sample liquid stream Direction.

Embodiment

In this case that Fig. 1 is shown embodiment, the example is characterized in, the structure of the device includes multichannel micro-fluidic Chip, the structure of the micro-fluidic chip include being bonded to each other the substrate 1 and cover plate 2 of installing together, the substrate 1 and cover plate 2 It is plate object or tablet, that face towards the cover plate 2 of the substrate 1 is contained to be formed via mould pressing process or etching technics Channel structure, the substrate 1 also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics Or the window structure that simple drilling technology is formed, it is bonded to each other the substrate 1 being installed together and is built into jointly with the cover plate 2 Micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the locations of structures of the pipeline be located at the substrate 1 with The interface zone that the cover plate 2 is bonded to each other, its side of the window is blocked by the cover plate 2 and opposite side opens, the structure of the window Position is exactly the locations of structures of the liquid pool, and 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 end sample introduction end liquid pool and terminal liquid pool, the position of sample introduction end 5 of the micro-fluidic chip Liquid pool, the sample introduction end 5 refers to the injection end position of detected solution during the micro-fluidic chip actual sample introduction, in the micro-fluidic core Then there is a terminal liquid pool position of terminal 6 of piece, and the terminal 6 refers to during the actual sample introduction test of the micro-fluidic chip it The terminal location that liquid flows in chip, the terminal 6 are located remotely from each other with the sample introduction end 5, and one end of the pipeline is with being located at sample introduction end 5 The sample introduction end liquid pool UNICOM, the other end of the pipeline with positioned at the micro-fluidic chip the terminal 6 the terminal liquid Pond 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 refer to that its locations of structures of the reference electrode refers to closer to the position of terminal 6, the backward Be the reference electrode locations of structures closer to the position of sample introduction end 5, the working electrode is by conductive electrode and patch The gold size sensitive membrane for having embedded tumor markers antibody being attached on the conductive electrode is formed, and parallel connection is presented in the construction of the pipeline Construction, the pipeline in parallel construction is made up of eight lateral parallel connections, the pipeline of the presentation parallel construction its Appearance profile is similar to the profile of parallel circuit, and the quantity of the working electrode is eight, the installing position of eight working electrodes Put respectively in eight laterals, and, the tumour in its top layer gold size sensitivity membrane structure of eight working electrodes Mark antibody is the eight kinds of tumor markers antibody materials that can be specifically bound to tumor markers antigen respectively, and this eight kinds anti- Body material is tumor markers antibody CA199, CA153, CA125, CA242, AFP, CEA, EB and β-HCG respectively, described anti- Original is the antigen of broad sense, and the antibody is the antibody of broad sense, its material of the working electrode be argent material, gold material, Column, sheet or thread, the substrate 1 is presented in carbon material or thermal decomposition conducting polymer material, its pattern of the working electrode Its material is dimethyl silicone polymer material, and its surface of substrate 1 is the surface of primary form, its meaning of the surface of the primary form Think 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 miniature ultrasonic transducer units 4, and, higher-order of oscillation electric signal transmission cable 3, the higher-order of oscillation telecommunication One end of number transmission cable 3 links together with the miniature ultrasonic transducer units 4, and the miniature ultrasonic transducer units 4 attach ground dress It is located at the position of the cover plate 2 of the micro-fluidic chip or the neighbouring terminal 6 of substrate 1；Its is main for the miniature ultrasonic transducer units 4 Function is in the actual sample introduction test of micro-fluidic chip, is changed using the sample introduction end 5 and the terminal 6 with the miniature ultrasonic Difference that can be on the distance between the installation position of device 4 difference and its ultrasonic intensity experienced, enter described in induced synthesis Difference between its interfacial tension of sample end 5 and the terminal 6 its interfacial tension, the boundary between the micro-fluidic chip both ends 5,6 Face tension difference can form pressure gap between the both ends 5,6 of the micro-fluidic chip, and the pressure gap can drive sample molten Liquid flows to the terminal 6；It is soft and have the substrate 1 of the dimethyl silicone polymer material of elasticity its function also include it is right with its The property that ultrasonic wave absorbs strongly, ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic chip, the terminal 6 arrives the sample introduction The rapid decrement of ultrasonic intensity is realized within limited short distance between end 5；And many silica dioxide granules, should Many silica dioxide granules are filled in the pipeline, and its tube chamber of the pipeline is filled out by many silica dioxide granules Full, for its particle size range of the silica dioxide granule between 10 microns and 200 microns, the silica dioxide granule is titanium dioxide silicon wafer Its unorganic glass of shared percentage by weight more than 80% of state particle, silica glass granule or silica composition Grain.

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

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

Involved miniature ultrasonic transducer units 4 are commercially available；It can also be customized to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal transmission cable 3 is commercially available；Can also to ultrasonic transducer producer customize or to Cable specialized factory customizes.

Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；Can also be to relevant speciality producer Customization.

The multi-channel electrochemical work station can be with commercially available；The multi-channel electrochemical work station can also be according to tool Body needs whereabouts specialised manufacturers to customize.

Each working electrode in this example structure and can be respectively via each special electricity to electrode and reference electrode Cable or say is being got lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as annex or saying interface connection of getting lines crossed.

In view of the pipeline of the presentation parallel construction its form foot that this case related text above expresses that it is described It is enough 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；Exempt from described in this case Epidemic disease compound refers to the immune complex of broad sense.

Claims (10)

1. the classifiable tumor markers in detecting micro flow control chip device that women is applicable, it is characterised in that the knot of the device Structure includes multichannel micro-fluidic chip, and the structure of the micro-fluidic chip includes being bonded to each other the substrate and cover plate of installing together, The substrate and cover plate are plate object or tablet, that face towards the cover plate of the substrate contain via mould pressing process or Etching technics formed channel structure, the substrate also containing be connected with the channel structure and pierce the substrate via stamper The window structure that skill, etching technics or simple drilling technology are formed, is bonded to each other the substrate being installed together and is total to the cover plate With the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto has been built into, the locations of structures of the pipeline is located at The interface zone that the substrate is bonded to each other with the cover plate, its side of the window is blocked by the cover plate and opposite side opens, 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 respectively The sample introduction end liquid pool and terminal liquid pool of position, the sample introduction end position of the micro-fluidic chip have it is one or more it is described enter Sample end liquid pool, the sample introduction end refers to the injection end position of detected solution during the micro-fluidic chip actual sample introduction, in the miniflow The terminal location of control chip then has a terminal liquid pool, when the terminal 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 are located remotely from each other with the sample introduction end, and one end of the pipeline is with being located at sample introduction end The sample introduction end liquid pool UNICOM, the other end of the pipeline with positioned at the micro-fluidic chip the terminal the terminal liquid pool UNICOM, and, sequentially or backward be respectively installed in working electrode in the pipeline on diverse location and to electrode and Reference electrode, the order refer to its locations of structures of the reference electrode closer to the terminal location, what the backward referred 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 formed, and structure in parallel is presented in the construction of the pipeline Make, the pipeline in parallel construction is made up of eight lateral parallel connections, and the pipeline that parallel construction is presented is outside it Shape profile is similar to the profile of parallel circuit, and the quantity of the working electrode is eight, the installation position of eight working electrodes Respectively in eight laterals, and, the tumour mark in its top layer gold size sensitivity membrane structure of eight working electrodes Will thing antibody is the eight kinds of tumor markers antibody materials that can be specifically bound to tumor markers antigen respectively, eight kinds of antibody Material is tumor markers antibody CA199, CA153, CA125, CA242, AFP, CEA, EB and β-HCG respectively, the antigen It is the antigen of broad sense, the antibody is the antibody of broad sense, and its material of the working electrode is argent material, gold material, carbon Column, sheet or thread, its material of the substrate is presented in material matter or thermal decomposition conducting polymer material, its pattern of the working electrode Matter is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, the surface of the primary form its be meant to Be the not primary form of the material by any surface chemical modification or any surface chemical modification surface, the device Structure also include miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, the higher-order of oscillation electric signal transmission One end of cable links together with the miniature ultrasonic transducer units, and the miniature ultrasonic transducer units are installed in the miniflow with attaching Control the position of the cover plate of chip or the neighbouring terminal of substrate；Its major function of the miniature ultrasonic transducer units is micro-fluidic When the actual sample introduction of chip is tested, using between the sample introduction end and the terminal and the miniature ultrasonic transducer units installation position Distance difference and its ultrasonic intensity experienced on difference, its interfacial tension of sample introduction end and institute described in induced synthesis State the difference between terminal its interfacial tension, the interfacial tension difference between the micro-fluidic chip both ends can be in the micro-fluidic core Pressure gap is formed between the both ends of piece, the pressure gap can drive sample solution to the end flow；Softness simultaneously has bullet Property the substrate of the dimethyl silicone polymer material its function also include with its property to the strong absorption of ultrasonic wave, to ultrasonic wave Absorbed strongly, and thereby realize and surpass within micro-fluidic chip terminal to the limited short distance between the sample introduction end The rapid decrement of intensity of acoustic wave；And many silica dioxide granules, many silica dioxide granules are filled in the pipeline Interior, its tube chamber of the pipeline is filled up by many silica dioxide granules, and its particle size range of the silica dioxide granule is between 10 Between micron and 200 microns, the silica dioxide granule is silica crystalline particles, silica glass granule or silica Its inorganic glass particles of shared percentage by weight more than 80% of composition.

2. the classifiable tumor markers in detecting micro flow control chip device that women according to claim 1 is applicable, its It is characterised by, it is capillary channel that the pipeline, which includes the lateral,.

3. the classifiable tumor markers in detecting micro flow control chip device that women according to claim 1 is applicable, its It is characterised by, the thermal decomposition conducting polymer is the electric conductivity formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated Material.

4. the classifiable tumor markers in detecting micro flow control chip device that women according to claim 1 is applicable, its Be characterised by, 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. the classifiable tumor markers in detecting micro flow control chip device that women according to claim 1 is applicable, its It is characterised by, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.

6. the classifiable tumor markers in detecting micro flow control chip device that women according to claim 1 is applicable, its It is characterised by, the cover plate its material in structure is dimethyl silicone polymer material.

7. the classifiable tumor markers in detecting micro flow control chip device that women according to claim 1 is applicable, its Be characterised by, the distance between the terminal and the sample introduction end between 3 centimetres and 10 centimetres, the cover plate and substrate its Thickness is between 1.0 millimeters and 5.0 millimeters.

8. the classifiable tumor markers in detecting micro flow control chip device that women according to claim 1 is applicable, its It is characterised by, its particle size range of the silica dioxide granule is between 100 microns and 200 microns, its inside diameter ranges of the pipeline Between 500 microns and 1000 microns.

9. the classifiable tumor markers in detecting micro flow control chip device that women according to claim 1 is applicable, its It is characterised by, the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission Its other end of cable is connected with the higher-order of oscillation electric signal generator.

10. the classifiable tumor markers in detecting micro flow control chip device that women according to claim 1 is applicable, its It is characterised by, for its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units between 2 milliwatts and 2000 milliwatts, this is miniature The frequency of its ultrasonic wave operationally launched of ultrasonic transducer is between 100KHz and 12MHz.