CN107754946A - Integrated women classifiable tumor mark joint inspection chip apparatus - Google Patents

Abstract

The present invention relates to a kind of integrated women classifiable tumor mark joint inspection chip apparatus, 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, there are some problems.This case main points are, the selected PDMS with ecosystem surface of substrate, and by the elastic clip that miniature ultrasonic transducer units are attached on its clamping limb with elastic force snap-in location the chip sample liquid stream terminal location, with driving force of the ultrasonic wave induced synthesis based on interfacial tension difference, its driving force couples running with Micropump simultaneously, collaboration drives test liquid to flow to terminal direction flowing, 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

Integrated women classifiable tumor mark joint inspection chip apparatus

Technical field

The present invention relates to a kind of integrated women classifiable tumor mark joint inspection chip apparatus, belongs to analysis test neck Domain.

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, as described above, the PDMS conduit 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 in the surface state after the modification of its surface or surface modification It is used within short-term；If having had been subjected to that ofer short duration period of validity, and still by force if use, due to surface State already again close to hydrophobic state, then certainly exists bigger flowing using usual Micropump driving sample liquid stream and hindered Power, so, just by increasing Micropump pump power and pumping pressure test liquid can only be forced to flow to target direction flowing, as above institute State, this PDMS material is soft, and sample liquid stream is pumped with too high, mechanical pumping pressure, will cause the substrate its Bubbling, expanded, distortion, deformation, also, this high-pressure situations occur for the conduit that sample introduction end includes sample introduction end near zone Under, the stripping between substrate and cover plate, this feelings also easily occur in the sample introduction end and its conduit of near zone and its periphery Under shape, sample solution flows in the crack for entering appearance of the stripping afterwards between the substrate and cover plate of formation everywhere, this Actually result in 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；In the case where carrying out liquid stream driving using additional Micropump merely, The above-mentioned problem exists all the time.As described above, if it is preposition not do any surface modification or surface modification etc. completely Operation, then, the above-mentioned problem will be even more serious, even without conduit bubbling described in sample introduction end and its near zone, swollen occurs The problems such as changing, being peeled off between distortion, deformation and substrate and cover plate, merely because the flow resistance is excessive, using high pressure Micropump Also sample liquid stream may not can be driven to be marched forward towards terminal side.

Fourth, 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, while solve to address above A series of problem, also, the solution is applied to build a kind of new can be directed to that to belong to women physical examination special Need the seven kinds of micro flow control chip devices that examination simultaneously while detection are carried out than more typical primary tumor mark paid close attention to.

The present invention solves the technical problem by following scheme, and the device that the program provides is a kind of integrated women allusion quotation Type co-detections of tumor markers in benign chip apparatus, it is characterised in that the structure of the device includes micro-fluidic chip, the micro-fluidic chip Structure include being bonded to each other installing substrate and cover plate together, the substrate and cover plate are plate object or tablet, should The channel structure via mould pressing process or etching technics formation is contained in that face towards the cover plate of substrate, is bonded to each other installation The substrate together has been built into the micro-fluidic chip containing pipeline configuration, the structure bit set of the pipeline jointly with the cover plate In the juncture area that the substrate and the cover plate are bonded to each other, the both ends of the pipeline respectively with the sample introduction end of the micro-fluidic chip and Terminal connects, and the sample introduction end is the injection end of the micro-fluidic chip sample solution, and the terminal is the actual sample introduction of the micro-fluidic chip The terminal that sample solution flows in its chip during test, the terminal is located remotely from each other with the sample introduction end, the terminal and the sample introduction end it Between distance between 3 centimetres and 10 centimetres, the terminal links together with terminal liquid pool, the wheel of its structure of the terminal liquid pool Exterior feature is in pond shape, pit shape or cup-shaped, and the terminal liquid pool is used to receive the sample solution for flowing to terminal via the pipeline, in the pipe In road on diverse location in order or backward is equiped with working electrode and electrode and reference electrode, the order are referred to For its locations of structures of the reference electrode closer to the terminal location, the backward refers to the reference electrode locations of structures more Close to the sample introduction end position, the working electrode is swollen by conductive electrode and the embedding being attached on the conductive electrode The gold size sensitive membrane of tumor markers antibody is formed, and the construction of the pipeline is presented parallel construction, the pipeline in parallel construction by Eight laterals are in parallel to be formed, and its appearance profile of the pipeline of the presentation parallel construction is similar to the wheel of parallel circuit Exterior feature, the quantity of the working electrode is eight, and the installation position of eight working electrodes is located at eight laterals respectively It is interior, and, the tumor markers antibody in its top layer gold size sensitivity membrane structure of eight working electrodes is to tumor-marker respectively Eight kinds of tumor markers antibody materials that thing antigen can be specifically bound, eight kinds of antibody materials are tumor markers antibody respectively CA199, CA153, CA125, CA242, AFP, CEA, EB and β-HCG, the antigen are the antigen of broad sense, and the antibody is wide The antibody of justice, its material of the working electrode are argent material, gold material, carbon material or thermal decomposition conducting polymer material Column, sheet or thread is presented in matter, its pattern of the working electrode, and its material of the substrate is dimethyl silicone polymer material, should Its surface of substrate is the surface of primary form, the surface of the primary form its be intended to refer to and do not repaiied by any surface chemistry The surface of the primary form of decorations or the material of any surface chemical modification, the structure of the device also include elastic clip, the elastic force Two opposite clamping limb snap-in locations of folder are in the position of the neighbouring terminal of the micro-fluidic chip, and at least in one Fixation is attached on the individual clamping limb and is equiped with miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, the height Frequency vibration swings one end of electric signal transmission cable and the miniature ultrasonic transducer units link together；The elastic clip provides a side Just the function that the device is disassembled；Its major function of the miniature ultrasonic transducer units be in the test of micro-fluidic chip actual sample introduction, Utilize the sample introduction end and the distance between the terminal and the miniature ultrasonic transducer units installation position difference and its institute The difference on ultrasonic intensity experienced, its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension it Between difference, the interfacial tension difference between the micro-fluidic chip both ends can be formed between the both ends of the micro-fluidic chip Pressure gap, the pressure gap can drive sample solution to the end flow；The polydimethylsiloxanes that are soft and having elasticity Its function of the substrate of alkane material includes, with its property to the strong absorption of ultrasonic wave, absorbing ultrasonic wave strongly, and thereby The rapid decrement of ultrasonic intensity is realized within micro-fluidic chip terminal to the limited short distance between the sample introduction end； And Micropump, the Micropump are connected with the sample introduction end, the Micropump is built-in Micropump or external Micropump；The function of the Micropump is, Interfacial tension difference between the both ends induced with the mechanicalness of Micropump pumping strength come the ultrasonic wave its brought Driving force support mutually, adjust mutually, be mutually coupled, pooled in a manner of Collaboration one driving test liquid flow direction The strength of the terminal direction flowing；Described its thickness of cover plate and substrate is between 1.0 millimeters and 5.0 millimeters；And permitted More silica dioxide granules, many silica dioxide granules are filled in the pipeline, and its tube chamber of the pipeline is by many Silica dioxide granule filled up, its particle size range of the silica dioxide granule is between 10 microns and 200 microns, the titanium dioxide Silicon grain is silica crystalline particles, silica glass granule or silica composition its shared percentage by weight 80% Inorganic glass particles above, the terminal liquid pool is interior to be filled with some high hydroscopic resin particles, its opening end quilt of the terminal liquid pool Breathable microporous film is covered.

Only for the word of high hydroscopic resin one art-recognized meanings of itself, come for the professional of chemical field Say, be known.

The high hydroscopic resin is commercially available.

Only for the word of breathable microporous film one art-recognized meanings of itself, for the professional of technical field of membrane, It is known.

The breathable microporous film is commercially available.

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.

Described miniature ultrasonic transducer units can certainly be all installed on two clamping limbs；But only install one Miniature ultrasonic transducer units are dealt with and used enough.

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

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

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

For example miniature piezoelectric pump of the Micropump, 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, 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.

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.

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；The higher-order of oscillation electric signal transmission cable Its other 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, 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 5 milliwatts and 5000 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.

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：

This case is flowed with dual drive coupling operating mode driving liquid stream in the pipeline 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 tumour marks The corresponding horseradish peroxidase-labeled that will thing antigen molecule is embedded by gold size sensitive membrane on electrode surface in each passage swells Tumor markers antibody 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 in elastic force described in the terminal of the micro-fluidic chip its close position snap-in location Folder, and installation miniature ultrasonic transducer units are attached on the clamping limb of the elastic clip, launched with the miniature ultrasonic transducer units low The ultrasonic wave of power, high-frequency band, meanwhile, using its strong absorbability to ultrasonic wave of dimethyl silicone polymer substrate, In shorter distance, it is, in from the terminal to the very short distance of only several centimeters yardsticks the sample introduction end, Reach the rapid decrement of ultrasonic intensity, the difference of the interfacial tension thereby caused at the both ends of the micro-fluidic chip, The pressure gap that this kind is formed by Ultrasonic Radiation itself is exactly one driving power of sample solution to the end flow Amount, while the driving force that it is gone back and Micropump is provided intercouples, Collaboration, above-mentioned two bursts of strength makes a concerted effort to drive examination in the lump Sample liquid stream flows in the pipeline to the terminal direction.

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.

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.

With the simultaneous Micropump of miniature ultrasonic transducer units in its structure of micro-fluidic chip, its function is, with this Its caused drive of the interfacial tension difference that the mechanicalness pumping strength of Micropump is come between the both ends of ultrasonic wave induction Amount of power is supported mutually, adjusts mutually, is mutually coupled, and is pooled in a manner of Collaboration described in one driving test liquid flow direction The strength of terminal direction flowing；The presence of the Micropump so that the miniature ultrasonic transducer units its ultrasonic wave emissive porwers can be by Appropriateness is allowed to reduce, this is particularly suitable for for the situation containing ultrasonic wave sensitive composition in detection object；And because this is miniature super The presence of acoustic wave transducer and its radiated ultrasonic wave, the micro-fluidic chip its both ends interfacial tension can be induced and difference occur And the special driving force for being directed to sample solution is thereby brought, meanwhile, due also to being filled out in its pipeline of this case micro-fluidic chip Fill the silica dioxide granule with hydrophilic nmature, then, in the scenario above, its resistance of flowing in the pipeline of sample liquid stream Power is greatly reduced, and correspondingly, its running resistance of the Micropump is greatly reduced, and so, the Micropump just can be with than relatively low pumping pressure Power carries out the pumping work for the sample solution, because mechanical pumping pressure is greatly reduced, therefore, such one Under kind of situation, be just not susceptible to because the sample introduction end caused by sample introduction end Micropump its mechanicalness pumping pressure is excessive and its near The problems such as stripping between the conduit bubbling in region, expansion, deformation, distortion and the region substrate and cover plate etc.；This case should Dual drive couples the scheme of running and added for the handling of sample fluid flow action, can allow for using ultrasound Intensity of wave, ultrasonic frequency, Micropump pump power, Micropump pumping pressure etc. multiple indexs are fast to be directed to the flowing of the flowing Rate, flowing action include flow forward or pause flowing or acceleration flowing etc. flowing action carry out multi-parameter and accurately manipulated；Such as It is upper described, the presence of the Micropump so that its ultrasonic wave emissive porwer of the miniature ultrasonic transducer units can be allowed to appropriate reduction, So, the feature additionally aids described its sensitive coating of working electrode of protection, is allowed to from ultrasound injury.

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, this kind be very cheap and the easily dimethyl silicone polymer material of processing and fabricating Material be just possible in the micro-fluidic chip its prepare, production, using etc. field play bigger effect.

The miniature ultrasonic transducer units have been installed in fixation on the elastic clip its clamping limb in this case structure, and the structure carries A function of facilitating the device to disassemble is supplied, in this way, the elastic clip just can together with miniature ultrasonic transducer units appended thereon It is enough to be easily mutually disengaged with the micro-fluidic chip, then, the component that the part can freely depart from just can circulate benignly it is heavy It is multiple to use many times；The architectural feature is advantageous to save the use cost of the device.

The framework of its large-scale integrated of this case micro-fluidic chip, it is determined among actual test application, to serum The requirement of sample is smaller, and this contributes to the body and mind damage for reducing related subject.

Brief description of the drawings

Fig. 1 is its rough outside side view of this case device.

In figure, 1 is elastic clip, and 2,7 be two clamping limbs of elastic clip respectively, and 3 be the terminal of the micro-fluidic chip, 4 be the sample introduction end of the micro-fluidic chip, and 5 be the substrate of dimethyl silicone polymer material, and 6 be cover plate, and 8 be miniature ultrasonic Transducer, 9 be higher-order of oscillation electric signal transmission cable, and 10 be tension spring, and 11 be infusion tube, and 12 be Micropump；In legend The spring clamp structure is only the legend structure of signal, and actual spring clamp structure is not limited to the legend spring clamp structure；In legend Arrow indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, the flow direction of its sample liquid stream.

Embodiment

In this case that Fig. 1 is shown embodiment, its main points of the example are that the structure of the device includes micro-fluidic chip, The structure of the micro-fluidic chip includes being bonded to each other the substrate 5 and cover plate 6 of installing together, and the substrate 5 and cover plate 6 are plate The conduit via mould pressing process or etching technics formation is contained in shape thing or tablet, that face towards the cover plate 6 of the substrate 5 Structure, it is bonded to each other the substrate 5 being installed together and has been built into the micro-fluidic core containing pipeline configuration jointly with the cover plate 6 Piece, the locations of structures of the pipeline are located at the juncture area that the substrate 5 is bonded to each other with the cover plate 6, the both ends of the pipeline respectively with The sample introduction end 4 of the micro-fluidic chip and terminal 3 connect, and the sample introduction end 4 is the injection end of the micro-fluidic chip sample solution, should Terminal 3 is the terminal of sample solution flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, the terminal 3 and the sample introduction end 4 are located remotely from each other, and the distance between the terminal 3 and the sample introduction end 4 are between 3 centimetres and 10 centimetres, the terminal 3 and terminal liquid pool Link together, the profile of its structure of the terminal liquid pool is in pond shape, pit shape or cup-shaped, and the terminal liquid pool is used to receive via this Pipeline flow to the sample solution of terminal 3, in the pipeline on diverse location in order or backward be equiped with working electrode and To electrode and reference electrode, the order refers to its locations of structures of the reference electrode closer to the position of terminal 3, institute State backward and refer to the reference electrode locations of structures closer to the position of sample introduction end 4, the working electrode is by electric conductivity electricity Pole and the gold size sensitive membrane for having embedded tumor markers antibody being attached on the conductive electrode are formed, the construction of the pipeline Parallel construction is presented, the pipeline in parallel construction is made up of eight lateral parallel connections, the institute that parallel construction is presented The profile that pipeline its appearance profile is similar to parallel circuit is stated, the quantity of the working electrode is eight, eight working electrodes Installation position respectively in eight laterals, and, its top layer gold size sensitivity membrane structure of eight working electrodes In tumor markers antibody be the eight kinds of tumor markers antibody materials that can be specifically bound to tumor markers antigen respectively, 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 be argent material, Column, sheet or silk is presented in gold material, carbon material or thermal decomposition conducting polymer material, its pattern of the working electrode Shape, its material of the substrate 5 is dimethyl silicone polymer material, and its surface of substrate 5 is the surface of primary form, the primary form Surface its be intended to refer to the primary shape of the not material by any surface chemical modification or any surface chemical modification The surface of state, the structure of the device also include elastic clip 1, and two opposite clamping limbs 2,7 snap-in locations of the elastic clip 1 are at this The position of the neighbouring terminal 3 of micro-fluidic chip, attach on a clamping limb at least in it is fixed be equiped with it is micro- Type ultrasonic transducer, in this example, the miniature ultrasonic transducer units 8 are fixed on clamping limb 7 by attaching, and, the higher-order of oscillation Electric signal transmission cable 9, one end of the higher-order of oscillation electric signal transmission cable 9 are connected to one with the miniature ultrasonic transducer units 8 Rise；All fixed respectively on two clamping limbs 2,7 miniature ultrasonic transducer units can also be installed, but in general, only one Installation miniature ultrasonic transducer units are just enough to deal with and are provided one using needs, the elastic clip 1 and facilitated the dress on individual clamping limb Put the function of disassembling；Its major function of the miniature ultrasonic transducer units 8 is in the actual sample introduction test of micro-fluidic chip, utilizes institute State the distance between sample introduction end 4 and the terminal 3 and the installation position of miniature ultrasonic transducer units 8 difference and it is experienced To ultrasonic intensity on difference, between its interfacial tension of sample introduction end 4 described in induced synthesis and the terminal 3 its interfacial tension Difference, the interfacial tension difference between the micro-fluidic chip both ends 3,4 can be between the both ends 3,4 of the micro-fluidic chip Pressure gap is formed, the pressure gap can drive sample solution to be flowed to the direction of terminal 3；It is soft and have elasticity this poly- two Its function of the substrate 5 of methylsiloxane material is included with its property to the strong absorption of ultrasonic wave, and ultrasonic wave is inhaled strongly Receive, and thereby realize ultrasonic intensity within micro-fluidic chip terminal 3 to the limited short distance between the sample introduction end 4 Rapid decrement；And Micropump 12, the Micropump 12 are connected with the sample introduction end 4；The function of the Micropump 12 is, with the Micropump 12 Interfacial tension difference its caused driving force that mechanicalness pumping strength is come between the both ends 3,4 of ultrasonic wave induction Amount is supported mutually, adjusts mutually, is mutually coupled, and one driving test liquid is pooled in a manner of Collaboration and flows to the terminal The strength of 3 directions flowing；Its thickness of the cover plate 6 and substrate 5 is between 1.0 millimeters and 5.0 millimeters；It is and many Silica dioxide granule, many silica dioxide granules are filled in the pipeline, and its tube chamber of the pipeline is by the two of many Silicon oxide particle is filled up, and its particle size range of the silica dioxide granule is between 10 microns and 200 microns, the silica Grain is silica crystalline particles, silica glass granule or silica composition its shared percentage by weight more than 80% Inorganic glass particles, is filled with some high hydroscopic resin particles in the terminal liquid pool, its opening end of the terminal liquid pool is breathed freely Microporous barrier is covered.

Arrow in legend indicate the micro-fluidic chip its in actual motion, by both ends 3,4 pressure differentials drive, its 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.

The Micropump 12 can customize to specialized factory.

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

Involved elastic clip 1 is commercially available.It is available for the commercially available alternative spring clamp structure and make that this case structure uses Type and size etc., quality is various, and specific elastic clip pattern can be selected as needed.

Involved miniature ultrasonic transducer units 8 are commercially available；It can also be customized to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal transmission cable 9 is commercially available；Can also be special to ultrasonic transducer producer or cable Industry producer customizes.

Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；It can also determine to relevant manufacturers System.

The Micropump both can be the Micropump of external form；The Micropump can also do into or say the embedded micro-fluidic chip The Micropump of the built in version of internal its sample introduction end structure position or the sample introduction end Near-neighbor Structure position, its basic structure key element with it is outer The Micropump for putting form 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 phase Close specialized factory's customization.

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. integrated women classifiable tumor mark joint inspection chip apparatus, it is characterised in that the structure of the device includes miniflow Chip is controlled, the structure of the micro-fluidic chip includes being bonded to each other the substrate and cover plate of installing together, and the substrate and cover plate are equal For plate object or tablet, the groove via mould pressing process or etching technics formation is contained in that face towards the cover plate of the substrate Road structure, it is bonded to each other the substrate being installed together and has been built into the micro-fluidic core containing pipeline configuration jointly with the cover plate Piece, the locations of structures of the pipeline are located at the juncture area that the substrate is bonded to each other with the cover plate, the both ends of the pipeline respectively with this The sample introduction end of micro-fluidic chip and terminal connection, the sample introduction end is the injection end of the micro-fluidic chip sample solution, the terminal It is the terminal of sample solution flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, the terminal and the sample introduction end are mutually remote From between 3 centimetres and 10 centimetres, the terminal is contacted one with terminal liquid pool for the distance between the terminal and the sample introduction end Rise, the profile of its structure of the terminal liquid pool be in pond shape, pit shape or cup-shaped, and the terminal liquid pool is used to receive via pipeline flowing To the sample solution of terminal, in the pipeline on diverse location in order or backward be equiped with working electrode 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 elastic clip, two opposite clamping limb snap-in locations of the elastic clip are in the neighbouring described of the micro-fluidic chip The position of terminal, fixation is attached on a clamping limb at least in and is equiped with miniature ultrasonic transducer units, and, it is high Frequency vibration swings electric signal transmission cable, and one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable are connected to Together；The elastic clip provides a function of facilitating the device to disassemble；Its major function of the miniature ultrasonic transducer units be When the actual sample introduction of micro-fluidic chip is tested, the sample introduction end and the terminal is utilized to install position with the miniature ultrasonic transducer units The distance between put the difference on difference and its ultrasonic intensity experienced, its interface of sample introduction end described in induced synthesis Difference between power and the terminal its interfacial tension, the interfacial tension difference between the micro-fluidic chip both ends can be micro- at this Pressure gap is formed between the both ends of fluidic chip, the pressure gap can drive sample solution to the end flow；It is soft And the substrate of the dimethyl silicone polymer material its function of having elasticity is included with its property to the strong absorption of ultrasonic wave, to super Sound wave is absorbed strongly, and thereby real within micro-fluidic chip terminal to the limited short distance between the sample introduction end The rapid decrement of existing ultrasonic intensity；And Micropump, the Micropump are connected with the sample introduction end, the Micropump is built-in Micropump or outer The Micropump put；The function of the Micropump is, with the mechanicalness pumping strength of the Micropump come with the both ends of ultrasonic wave induction it Between interfacial tension difference its caused driving force support mutually, adjust mutually, be mutually coupled, in a manner of Collaboration Pool the strength that one driving test liquid flows to the terminal direction flowing；Described its thickness of cover plate and substrate is between 1.0 Between millimeter and 5.0 millimeters；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, the terminal liquid pool is interior to be filled with some high hydroscopic resins Particle, its opening end of the terminal liquid pool are covered by breathable microporous film.

2. integrated women classifiable tumor mark joint inspection chip apparatus according to claim 1, it is characterised in that institute It is capillary channel to state pipeline to include the lateral.

3. integrated women classifiable tumor mark joint inspection chip apparatus according to claim 1, it is characterised in that institute It is the conductive material formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated to state thermal decomposition conducting polymer.

4. integrated women classifiable tumor mark joint inspection chip apparatus according to claim 1, it is characterised in that institute State working electrode width or diameter between 0.1 micron to 2000 microns, and, the length of the working electrode is micro- 1 Rice is between 15000 microns.

5. integrated women classifiable tumor mark joint inspection chip apparatus according to claim 1, it is characterised in that institute The thickness of gold size sensitive membrane is stated between 10 nanometers and 200 nanometers.

6. integrated women classifiable tumor mark joint inspection chip apparatus according to claim 1, it is characterised in that knot The cover plate its material in structure is dimethyl silicone polymer material.

7. integrated women classifiable tumor mark joint inspection chip apparatus according to claim 1, it is characterised in that institute It is miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump to state Micropump.

8. integrated women classifiable tumor mark joint inspection chip apparatus according to claim 1, it is characterised in that should Its particle size range of silica dioxide granule is between 100 microns and 200 microns, and its inside diameter ranges of the pipeline are between 500 microns Between 1000 microns.

9. integrated women classifiable tumor mark joint inspection chip apparatus according to claim 1, it is characterised in that should The structure of micro fluidic device also includes higher-order of oscillation electric signal generator, its other end of the higher-order of oscillation electric signal transmission cable It is connected with the higher-order of oscillation electric signal generator.

10. integrated women classifiable tumor mark joint inspection chip apparatus according to claim 1, it is characterised in that Between 5 milliwatts and 5000 milliwatts, the miniature ultrasonic changes its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units The frequency of its ultrasonic wave operationally launched of energy device is between 100KHz and 12MHz.