CN107282145A - The female tumor mark joint inspection chip apparatus of many type of drive coupling runnings - Google Patents
The female tumor mark joint inspection chip apparatus of many type of drive coupling runnings Download PDFInfo
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0609—Holders integrated in container to position an object
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0887—Laminated structure
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/16—Surface properties and coatings
- B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
Abstract
The present invention relates to a kind of female tumor mark joint inspection chip apparatus of many type of drive coupling runnings, belong to analysis testing field.The substrate for the classifiable tumor markers in detecting micro-fluidic chip that women is applicable is made so that PDMS is dimethyl silicone polymer, has price and technologic advantage, but also have any problem；This case is intended to overcome the difficulty.This case main points are, the selected PDMS with ecosystem surface of substrate, and its neighbor positions fixes installing miniature ultrasonic transducer units in the test liquid stream terminal of the micro-fluidic chip, simultaneously, ultrasonic wave damper is installed at the sample introduction end of the micro-fluidic chip, reach ultrasonic intensity rapid decrement in short distance, so as to form interfacial tension difference at the two ends of the chip, difference offer is a kind of to drive the strength that test liquid stream flows along hydrophobic capillary channel to the terminal direction, the strength with Micropump its mechanicalness pumping strength for being included in structure while intercouple, Collaboration.
Description
Technical field
The present invention relates to a kind of female tumor mark joint inspection chip apparatus of many type of drive coupling runnings, belong to analysis test
Field.
Background technology
Tumor markers (tumor marker, TM) refers in the generation and breeding of tumour, is produced in itself by tumour cell
Raw either reacted by body tumour cell and produce, reflection tumour exist and growth a class material, including protein,
Hormone, enzyme (isodynamic enzyme) and oncoprotein etc..The tumor markers in blood samples of patients or body fluid is chemically examined, can be in cancer screening
Early detection tumour, and observe the curative effect of oncotherapy and judge patient's prognosis.The tumor markers clinically commonly used at present has：
(1) alpha-fetoprotein (AFP) is the mark of the tumours such as primary carcinoma of liver, carcinoma of testis, oophoroma；(2) carcinomebryonic antigen (CEA) is digestion
The mark of the tumours such as system tumor, lung cancer, breast cancer；(3) CA125 (CA125) is the mark of the tumours such as oophoroma；
(4) CA153 (CA153) is the mark of the tumours such as breast cancer；(5) CA19-9 (CA19-9) is digestive system tumor
Mark；(6) CA724 (CA724) is the mark of the tumours such as stomach cancer, oophoroma；(7) carbohydrate antigen 242 (CA242)
For the mark of digestive system tumor；(8) CA50 (CA50) is the mark of the tumours such as digestive system tumor, breast cancer, lung cancer
Thing；(9) CYFRA21-1 (Cy211) is the mark of the tumours such as non-small cell lung cancer；(10) neuronspecific enolase (NSE)
For the mark of the tumours such as ED-SCLC, neuroendocrine tumor；(11) PSA (PSA) is prostate cancer
Tumor markers；(12) human chorionic gonadotrophin (HCG) is that embryonic cell carcinoma, trophoblastic tumor (suede cancer, vesicular mole) etc. are swollen
The mark of knurl；(13) thyroglobulin (TG) is the mark of thyroid cancer；(14) ferritin (SF) is digestive system tumor, liver
The mark of the tumours such as cancer, breast cancer, lung cancer；(15) B2M (β 2-MG) is in chronic lymphocytic leukemia, lymph
Raised in the patient body fluids such as knurl, myeloma, lung cancer, thyroid cancer, nasopharyngeal carcinoma；(16) squamous cell antigen (SCC) be cervical carcinoma,
The tumor markerses such as lung squamous cancer, the cancer of the esophagus.The tumor markers overwhelming majority clinically detected at present is not only present in malignant tumour
In, exist in benign tumour, embryonic tissue, even in normal structure.Therefore, tumor markers has dynamic chek and multinomial
Joint inspection is more valuable.So for numerous tumor markerses, clinically how to selectDifferent tumours understands some phases
To special tumor markers, such as CA153 often appears in breast cancer；CEA often appears in intestinal cancer, stomach cancer；CA19-9 is often appeared in
Intestinal cancer, cancer of pancreas；CA125 often appears in oophoroma etc..Clinician can be according to the different mark of different tumor examinations.
Same tumour or different types of tumour can have one or more of tumor markerses abnormal；Same tumor markers can be in difference
Tumour in occur.To improve the additive diagnostic value of tumor markers and determining which kind of mark can be supervised as the follow-up after treatment
Index is surveyed, tumor markers joint-detection, the complementary tumor markers group of several sensitivity of reasonable selection, specific performance can be carried out
Into best of breed, joint-detection is carried out.In general the joint-detection of tumor markers can improve the accuracy to diagnosing tumor.
Only with regard to Diagnostic Value of Several Serum Tumor Markers its joint-detection background of related itself general picture or overview for, may refer to
Lower Chinese invention patent application case：CN200410041175.3、CN200510026780.8、CN200610040051.2、
CN200910064647.X。
Only for the microfluidic chip technology overall general picture of itself, famous micro-fluidic expert Mr. Lin Ping Cheng may refer to soon
Before the monograph " diagram Microfluid based Lab on a chip " that goes out, the monograph is published via Science Press, and the monograph is for micro-fluidic
Past of technology, now, and, in terms of vision of the future etc., suffer from detail, be deep into long discussion of detail.
So, the focal issue that this case that to have a talk below is paid special attention to.
The basic framework of micro-fluidic chip, including it is etched with the substrate of small fluid course and the cover plate fit together therewith,
Small fluid course on the substrate, assembling upper cover plate before, it is apparent on see to be exactly some micro-channels, wait until thereon
After covering cover plate, just real closure forms the small fluid course, and the conduit inner surface of the micro-channel is together with surround this
The part cover plate of micro-channel constitutes described small fluid course together；So, it is clear that this after assembling is completed is small
Fluid course, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, in the micro-channel
The state or property on surface substantially determine the integrality or property of the small fluid course；Therefore say, this is built in base
The inner surface state or inner surface property of micro-channel on piece are key factors；In principle, it is any to keep or protecting substantially
The material of its solid forms is held, can be used to make substrate and cover plate, such as, the material that can act as substrate and cover plate can be with
It is monocrystalline silicon piece, quartz plate, sheet glass, high polymer such as dimethyl silicone polymer, polymethyl methacrylate, makrolon etc.
Deng；Certainly, the selection of substrate and the selection of cover plate be able to can also be differed with identical；From material consumption, manufacture difficulty and
From the point of view of in terms of application popularization prospect etc., between these materials exist not small difference, the especially selection of that substrate, influence compared with
Greatly.
In various substrate making materials, dimethyl silicone polymer, i.e. PDMS, comparatively very easily shaping, so
Substrate on make that micro-channel is extremely simple, and the lower cost for material makes substrate with the polydimethyl siloxane material,
Micro-channel is being suppressed or etched thereon, and is being engaged with the cover plate that the cheap material such as glass or polypropylene or other plastic sheets makes,
It is a kind of more satisfactory selection seemingly；Certainly, patch material can also select to use cheap polydimethyl siloxane material：
So, this substrate selection is the scheme of polydimethyl siloxane material, and material is extremely cheap, makes extremely simple, seems and should also be as
It is extremely easy to popularize, promotes.
But, thing is really not so simple.
First, this polydimethyl siloxane material, that is, the material that the letter PDMS that abridges is referred to, itself are a kind of strong
Hydrophobic material, micro-channel is built on this material, if without being operated for the modified of the micro-channel surface, then,
After overall assembling is completed, that is, cover after cover plate, because the micro-channel its inner surface in structure occupies most liquid circulation
The inner surface in road, then, its strong hydrophobic property of the PDMS micro-channels inner surface, is deciding factor, it can cause class
Be similar to the aqueous solution the fine liquid stream of polar liquid by becoming very difficult, its flow resistance is big, or even general Micropump is all
It is difficult to promote, certainly, if cover plate also selects to use the PDMS material, then, problem is substantially identical, similar；
Therefore, among prior art, modification is modified particular for the micro-channel inner surface on the PDMS material, is necessary
Operation；So, this is pretty troublesome for the modified operation of PDMS micro-channel inner surfacesThat falls nor this problem, structure
Perplex into serious technical, be another problem：PDMS polymer molecules tool inside its body phase of this PDMS material substrate
There are PDMS polymer molecules inside the characteristic for diffusing to the surface, migrating automatically, this substrate body phase to diffuse to the surface, move automatically
The characteristic of shifting, will cause the state after modification by its inner surface of that micro-channel of surface modifying and decorating can not maintain foot
Enough long time, the holding time for micro-channel its inner surface state after that is surface-modified is substantially only sufficient to complete in laboratory
The time of portion's test experiments needs；In other words, by surface modification or the PDMS micro-channel inner surfaces of surface modification, its
The surface state that is formed can not be lasting after modification or after saying modification, but soon automatically tend to or say and become surface again and change
Surface state before property, returns to the strong hydrophobic surface state of that script in the shorter time, then, just think,
Such micro-fluidic chip can largely make, mass storage, be widely popularized, and answer is it is obvious that is, impossible.
Micro-channel on this PDMS material, can not pump similar to the fine liquid stream of polar solvent of the aqueous solution if not doing surface modification
Send and pass through, chip also cannot just be used；And if having done surface modification, the state after its modification can not be persistently kept again, also
Being equally can not popularization and application.
So, how to accomplish that substrate can either be made using cheap PDMS material, and table in the micro-channel can be released
Face decorating state can not persistently, chip can not largely make, largely lay in so that be widely popularized it is such a make this area it is numerous specially
The puzzlement that industry personnel are entangled with for a long time, the highly difficult problem that exactly one its obvious technology barrier can not despise.
Be present many year in the highly difficult problem, so far, not yet properly settled.
Second, the PDMS material of non-surface modification, above it is stated that, its surface is strongly hydrophobic, this strong hydrophobic
Material surface and also another problem, that is, this strong hydrophobic PDMS surfaces can adsorb large biological molecule, and
And, these adsorbed large biological molecules can also further depression further on PDMS surfaces, gradually fall into gradually deep, directly
It is trapped in heavy within the body phase of PDMS substrates, in fact, this process is partly also due to inside PDMS material body phase
Polymer molecule, which has, to be diffused to the surface, caused by travel motion；Such case, can also be explained from another angle, i.e.
Continuously from inside PDMS body phases to its diffusion into the surface, migration those polymer molecules, its result moved, be by
Gradually those are involved within the body phase of PDMS substrates by the large biological molecule of adsorption, briefly, these are inhaled
Attached large biological molecule is exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up large biological molecule
Phenomenon, the influence caused by it necessarily causes the severe deviations of all kinds of test data of experiment for being related to large biological molecule.
As described above, be the problem of PDMS substrates, its not only adsorption large biological molecule, and swallow up large biological molecule,
So, as the large biological molecule of experiment test object, its disappearance will not stop because the absorption of surface saturation, but, no
It is disconnected adsorbed, also constantly swallowed up.
On PDMS substrates in related experiment test process its body phase constantly swallow up test associated biomolecule macromolecular phenomenon, separately
It is to say that one kind, which is explained, there are substantial amounts of Minute pores in PDMS body phases, and associated biomolecule macromolecular is by after adsorption, depression
Into these Minute pores, and then swallowed up；However, inventor thinks, those can allow the air point of miniature scale
Son squeezes into the Minute pores therebetween, and being not equal to them also can directly allow that the large biological molecule of relative large scale enters, and two
Person's difference on yardstick is huge, must not make sweeping generalizations.Explanation is bypassed, in any case, the biology of object is analyzed as dependence test
Macromolecular is adsorbed by PDMS substrate micro-channels inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is known objective
The phenomenon of presence.
, can be from containment PDMS surfaces to life in order to prevent this PDMS substrate bodies relative to the effect of swallowing up of large biological molecule
The absorption of thing macromolecular is addressed, and method is chemically modified modification aiming at the PDMS material surface, for
For PDMS is the situation of substrate material, modification exactly is chemically modified to the surface of described micro-channel part, by changing
The micro-channel inner surface of modification is learned, its absorption to large biological molecule can be contained, and then avoid large biological molecule quilt
PDMS substrate body phases are swallowed up；But, or that old problem, that is, the chemical modification on PDMS material surface changes
Surface state after property can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface automatically,
The process of migration, soon can become that micro-channel inner surface state being modified by surface chemical modification again script strong and dredge
Water and the state of strong adsorption large biological molecule, in other words, no matter how professionals in the field turn from side to side, the PDMS
Its micro-channel inner surface of substrate is always rapidly to strong hydrophobic surface state evolution.
So, how can either obtain that PDMS material price is extremely cheap, substrate makes extremely easy benefit, can reach again
Growth stage contains absorption process of the PDMS substrate micro-channel inner surfaces to large biological molecule, and then prevents PDMS substrate body phases
The effect of swallowing up to large biological molecule so that related chip manufactured goods are able to maintain that a prolonged enough, rational shelf-life,
It is exactly a very intractable problem.The problem makes the numerous specialties in this area as another problem addressed above, equally
Personnel are entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise.The hardly possible
Also be present many year in topic, so far, also not yet properly settled.
Third, as described above, the PDMS micro-channel inner surfaces are strongly hydrophobic, and targetedly surface chemical modification or come to the surface
Learn modification to be difficult to again persistently, therefore, actually can only still belong to effective short in the surface state after the modification of its surface or surface modification
It is used within phase；If have passed through that ofer short duration period of validity, and still by force if use, due to surface shape
State already again close to hydrophobic state, is then certainly existed than larger flow resistance using usual Micropump driving test liquid stream,
So, just test liquid can only be forced to flow to target direction flowing by increasing Micropump pump power and pumping pressure, as described above,
This PDMS material is soft, pumps test liquid stream with too high, machinery pumping pressure, causing the substrate, it enters
Bubbling, expanded, distortion, deformation, also, this high-pressure situations occur for the micro-channel that sample end includes sample introduction end near zone
Under, also easily occur the stripping between substrate and cover plate, this feelings in the sample introduction end and its micro-channel of near zone and its periphery
Under shape, sample solution flows in the crack of the appearance between the substrate and cover plate that are formed after the entrance stripping everywhere, this reality
Border causes the damage of the micro-fluidic chip；Certainly, it is not in place if surface modification or surface modification script, also result in
There is said circumstances within the of short duration usual term of validity；It is above-mentioned in the case where carrying out liquid stream driving using additional Micropump merely
The problem exists all the time.If be modified or the pre action such as surface modification as described above, not doing any surface completely,
So, the above-mentioned problem will be even more serious, even without occur micro-channel bubbling described in sample introduction end and its near zone, it is expanded,
Between distortion, deformation and substrate and cover plate the problems such as peel off, merely because the flow resistance is excessive, using high pressure Micropump also not
Test liquid stream must can be driven to be marched forward towards terminal side.
The content of the invention
The technical problems to be solved by the invention are to provide a package solution, while solving three addressed above
The a series of problem actually mutually involved together of aspect, also, the solution is a kind of new applied to building
It can especially need seven kinds paid close attention to than more typical primary tumor mark progress examination simultaneously, simultaneously for belonging to women physical examination
The micro flow control chip device of detection.
The present invention solves the technical problem by following scheme, and the device that the program is provided is a kind of many type of drive coupling fortune
The female tumor mark joint inspection chip apparatus of work, this case main points are that the structure of the device includes micro-fluidic chip, the miniflow
Controlling the structure of chip includes the substrate and cover plate of installing bonded to each other together, and the substrate and cover plate are plate object or sheet
The channel structure via mould pressing process or etching technics formation is contained in thing, that face towards the cover plate of the substrate, bonded to each other
The substrate being installed together has been built into the micro-fluidic chip containing pipeline configuration, the locations of structures of the pipeline jointly with the cover plate
Positioned at the substrate and cover plate juncture area bonded to each other, the two ends of the pipeline respectively with the sample introduction end of the micro-fluidic chip and
Terminal is connected, and the sample introduction end is the injection end of the micro-fluidic chip sample solution, and the terminal is that the actual sample introduction of the micro-fluidic chip is surveyed
The terminal that sample solution flows in its chip during examination, the terminal is located remotely from each other with the sample introduction end, between the terminal and the sample introduction end
Distance between 3 centimetres and 10 centimetres, in the pipeline on diverse location in order or backward be equiped with working electrode and
To electrode and reference electrode, the order refers to its locations of structures of the reference electrode closer to the terminal location, described
Backward refers to the reference electrode locations of structures closer to the sample introduction end position, the working electrode by conductive electrode and
The gold size sensitive membrane for having embedded tumor markers antibody being attached on the conductive electrode is constituted, and the construction of the pipeline is presented in parallel
Construction, the pipeline in parallel construction is made up of eight lateral parallel connections, and the pipeline of the presentation parallel construction is outside it
Shape profile is similar to the profile of parallel circuit, and the quantity of the working electrode is eight, the installation position point of eight working electrodes
Not Wei Yu in eight laterals, and, the tumor markers in the sensitive membrane structure of its top layer gold size of eight working electrodes
Antibody is the eight kinds of tumor markers antibody materials that can be specifically bound to tumor markers antigen, eight kinds of antibody materials point respectively
It is not tumor markers antibody CA199, CA153, CA125, CA242, AFP, CEA, EB and β-HCG, the antigen is
The antigen of broad sense, the antibody is the antibody of broad sense, and its material of the working electrode is argent material, gold material, carbon
Column, sheet or thread, its material of the substrate is presented in material or thermal decomposition conducting polymer material, its pattern of the working electrode
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
Not by any surface chemical modification or the surface of the primary form of the material of any surface chemical modification, the structure of the device
Also include miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, the higher-order of oscillation electric signal transmission cable
One end links together with the miniature ultrasonic transducer units, and the miniature ultrasonic transducer units are installed in the micro-fluidic chip with attaching
The position of the neighbouring terminal of cover plate or substrate；Its major function of the miniature ultrasonic transducer units be micro-fluidic chip it is actual enter
When sample is tested, the ultrasonic wave launched using it is reduced between sample solution and the inwall of its inner passage of micro-fluidic chip
Interfacial tension, can be compatible, also, is installed using the sample introduction end and the terminal with the miniature ultrasonic transducer units
Difference in the distance between position difference and its ultrasonic intensity experienced, its interface of sample introduction end described in induced synthesis
Interfacial tension difference between difference between power and the terminal its interfacial tension, the micro-fluidic chip two ends can be in the miniflow
Pressure gap is formed between the two ends for controlling chip, the pressure gap can drive sample solution to the end flow；This is miniature super
Acoustic wave transducer its function also include with its ultrasonic wave launched check large biological molecule contained in sample its in the miniflow
Control the absorption on chip its inner passage inner surface, and then check the substrate of the dimethyl silicone polymer material its body phase to the biology
The effect of swallowing up of macromolecular；It is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and include with it to ultrasonic wave
The property absorbed strongly, is absorbed strongly to ultrasonic wave, and thereby in the micro-fluidic chip terminal between the sample introduction end
The rapid decrement of ultrasonic intensity is realized within limited short distance；And, Micropump, the Micropump is connected with the sample introduction end；This is micro-
The function of pump is that the interfacial tension between the inwall of the sample solution and its inner passage of micro-fluidic chip is made by the ultrasonic wave
With and reduce, under the increased precondition of alternate compatibility, come with the mechanicalness pumping strength of the Micropump and ultrasonic wave induction
Interfacial tension difference its driving force brought between the two ends is supported mutually, adjusts mutually, is mutually coupled, to cooperate with
The mode of running pools the strength that one driving test liquid flows to the terminal direction flowing；Described its thickness of cover plate and substrate is equal
Between 1.0 millimeters and 5.0 millimeters；And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular
Or it is bar-shaped；Its material of the ultrasonic wave damper is microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip,
The elastic force accompanies two clamping limbs, and the medial surface of each clamping limb is relative with the medial surface of another clamping limb, one of clamping
The medial surface of arm is close to the sample introduction end of the micro-fluidic chip, and the medial surface of another clamping limb is close to the ultrasonic wave damper,
The elastic clip with its gripping strength by the sample introduction end of the micro-fluidic chip and the ultrasonic wave damper it is bonded to each other clip together, should
The strong consumption to ultrasonic wave that ultrasonic wave damper is brought with its material, is further supported at the micro-fluidic chip end
The rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end is held, and is thereby further expanded described
Difference between its interfacial tension of sample introduction end and the terminal its interfacial tension.
The tumor markers antibody is the antibody of broad sense, and the antibody of the broad sense refers to possessing antibody function or functionally similar
Can occur to combine and formed immune complex or immune compound with the various involved tumor markerses of corresponding clinic in antibody
The material of the analog of thing；The tumor markers antigen is the antigen of broad sense, and the antigen of the broad sense is referred to can be using accordingly
Antibody or be functionally similar to antibody material carry out enzyme mark detection it is various it is clinical involved the need for differentiate, the tumor-marker of detection
Thing.
The word of Micropump one art-recognized meanings of itself are known for the professional in micro-fluidic chip field.
The Micropump both can be the Micropump of external form；The Micropump can also be done into or say inside the embedded micro-fluidic chip
The Micropump of the built in version of its sample introduction end structure position or the sample introduction end Near-neighbor Structure position.
The Micropump such as miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.
The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and tumor markers antibody-solutions uniformly, uses point sample instrument
Point sample is coated on specified structure position, and forms its drying and forming-film.Tumor markers antibody in the gold size sensitive membrane is equal
The tumor markers antibody marked for horseradish peroxidase or glucose oxidase, the gold size sensitive membrane has been included as fixing
Above-mentioned each tumor markers antibody and introduce complementary medium therein, the complementary medium for example chitosan, cellulose acetate,
Gelatin is therein a kind of or their mixture.
The pipeline in the microfluidic chip structure includes the lateral, and its internal diameter size may each be arbitrarily selected
Size, still, for less with the consideration in terms of prepare liquid sample and reduction reagent loss, the pipeline includes described as far as possible
The passage of the preferred capillary level of lateral, the passage of the capillary level implies that the interior of its internal diameter and the capillary on ordinary meaning
The suitable passage in footpath.The shape of cross section of its inner passage of capillary can be arbitrary shape, the shape of cross section example
Such as circular, oval, square, rectangle, bar shaped, naturally it is also possible to be arbitrarily the presence of the linear of bending, also, the hair
The interior shape of tubule is with the extension of pipeline, and the shape of cross section of different parts can also allow to be different shapes.Only with regard to hair
For the word of tubule one, its art-recognized meanings is known.
What is be related in structure is the electrode of microsize to electrode and reference electrode, and its electrode shape may each be any choosing
Fixed shape, the arbitrarily selected shape such as column, sheet, strip or thread etc..It is described to electrode and the ginseng
Art-recognized meanings than the electrode vocabulary of itself are known.
It is public only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field
Know.
Various sizes, variously-shaped ultrasonic transducer are commercially available；Commercially available miniature ultrasonic transducer units its sizes can be with
It is small to the magnitude only calculated with millimeter.
Only with regard to miniature ultrasonic transducer units its technique for fixing on general industry application solid body surface itself and
Speech, is known general technology for the professional in ultrasonic technology field.This case is not to this expansion superfluous words.
Only with regard to naked PDMS substrates itself micro-channel molding or lithographic technique for, be open-and-shut known technology.
The industrial products market of involved its all size of higher-order of oscillation electric signal transmission cable is on sale.
The structure of the micro fluidic device can also include higher-order of oscillation electric signal generator；The higher-order of oscillation electric signal transmission electricity
Its other end of 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, for the professional in ultrasonic technology field, be
It is simple and known；The higher-order of oscillation electric signal generator can be customized to ultrasonic instrument specialized factory.
The preferred scope of its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units be between 2 milliwatts and 2000 milliwatts it
Between；The preferred scope of the frequency of its ultrasonic wave operationally launched of the miniature ultrasonic transducer units be between 100KHz with
Between 12MHz.
This case device can further include some annexes, the annex such as multiple tracks electrochemical workstation etc., institute certainly
The art-recognized meanings for stating multiple tracks electrochemical workstation are known.Each working electrode for being related in this case microfluidic chip structure and
, can be respectively via corresponding special the corresponding interface got lines crossed with the multiple tracks electrochemical workstation to electrode and reference electrode etc.
Coupled.It is described that special to get lines crossed be for each the corresponding interface of each electrode and the multiple tracks electrochemical workstation is carried out into phase
The private cable being mutually coupled with.The micro-fluidic chip in this case device, its structure can also include micro-valve, the number of the micro-valve
Amount is not limited, according to actual needs, and the micro-valve can be installed in any required position installed in the microfluidic chip structure；
The word of micro-valve one is for the professional of micro fluidic chip technical field, and the art-recognized meanings of itself are known；The micro-valve
The manufacturing technology of itself and the use of technology is also known；The component that the micro-valve is not required.
The diameter of the working electrode can allow to be that any setting is easily installed the suitable diameter used, it is however recommended to
Or say preferred its scope of the diameter between 0.1 micron to 2000 microns；The length of the working electrode can permit
Permitted to be that any setting is easily installed the length used, it is however recommended to or to say preferred its scope of the length be at 1 micron
To between 15000 microns.
The gold size for being installed in the working electrode surface layer by spraying or point sample instrument point sample or the coating of other appropriate process is quick
Feel film, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness, still, push away
Preferred thickness is between 10 nanometers and 200 nanometers in other words for the thickness recommended.
The cover plate in chip structure, its material can allow to be any electrical insulating property material, for example：Polypropylene, glass
Glass, polymethyl methacrylate, dimethyl silicone polymer, etc., in order to make smaller size of micro-fluidic chip, such as do
Realized into the micro-fluidic chip of only 2.0 centimetres to 3.0 centimetres of super-small of length, and in the extremely short distance to ultrasonic wave
Extremely fast decay, can preferably dimethyl silicone polymer be used as cover plate.Certainly, selected on large-sized micro-fluidic chip
It is used as the cover plate using dimethyl silicone polymer, is also that this case technical scheme is allowed.
The preferred scope of the distance between the terminal and the sample introduction end is between 3 centimetres and 10 centimetres.
Described its thickness of cover plate and substrate can allow be any setting be easy to assembling thickness, the thickness of recommendation or say preferably
Thickness be between 1.0 millimeters and 5.0 millimeters.Less thickness is conducive to saving material.
Described its size of ultrasonic wave damper is not limited, and described its length of ultrasonic wave damper, width, thickness may each be according to need
The arbitrary size to be set.
It is known in field of rubber technology only for the word of microcellular rubber one art-recognized meanings of itself.
The microcellular rubber is commercially available.
It is known in field of rubber technology only for the word of sponge rubber one art-recognized meanings of itself.
The sponge rubber is commercially available.
It is known in technical field of macromolecules only for the word of microporous polyurethane elastomer one art-recognized meanings of itself.
The polyurethane micropore elastomer material is commercially available.
The microcellular rubber preferred microporous silicon rubber or micropore fluorubber.
It is known in field of rubber technology only for the word of micropore silicon rubber one art-recognized meanings of itself.
The microporous silicon Rubber market is on sale.
It is known in field of rubber technology only for the word of micropore fluorubber one art-recognized meanings of itself.
The micropore fluorubber is commercially available.
The word of elastic clip one art-recognized meanings of itself are known.
The elastic clip is commercially available.
The application method of this case micro-fluidic chip：
This case is flowed with dual drive coupling operating mode driving liquid stream in the capillary channel of eight channel microfluidic chip,
Eight kinds of classifiable tumor mark diagnostic antigens are detected respectively using eight passage electrochemical analytical instruments.
The specific detection of this case micro-fluidic chip is as follows using step：
1st, blood serum sample liquid is added in micro-pipe road, under dual drive coupling operating mode driving, various tumor markerses
The tumor-marker for the corresponding horseradish peroxidase-labeled that antigen molecule is embedded by gold size sensitive membrane on electrode surface in each passage
Thing antibody capture.
2nd, the tumor markers antigen in the tumor markers antibody and blood serum sample of horseradish peroxidase-labeled forms immune multiple
Compound.
3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, using the above-mentioned reaction of amperometric detection
Caused curent change, is derived from the species and content of various analytes.
4th, result is subjected to comprehensive analysis, comprehensive diagnos is carried out to tumor markers antigen.
Changed it is an advantage of the invention that installing miniature ultrasonic in its close position attaching of the terminal of the micro-fluidic chip
Can device, it is launched using the miniature ultrasonic transducer units low-power, the ultrasonic wave of high-frequency band so that without coming to the surface
The compatibility learned between strong hydrophobic its tube wall of micro-fluidic chip internal pipeline and the test object aqueous solution of modification significantly increases
Plus, this is test liquid stream by there is provided a realistic possibility；Meanwhile, using dimethyl silicone polymer substrate its to ultrasound
The strong absorbability of ripple, in shorter distance, it is, from the terminal to only several centimeters the sample introduction end
In the very short distance of yardstick, reach the rapid decrement of ultrasonic intensity, thereby cause institute at the two ends of the micro-fluidic chip
The difference of interfacial tension is stated, the difference of the interfacial tension between the two ends can cause a kind of driving force, and this kind is poor because of interfacial tension
Its function of driving force is to drive test liquid stream in strong hydrophobic capillary channel originally to the terminal side caused by different
To flowing；And the simultaneous Micropump in structure, its function is, leads in the sample solution and the micro-fluidic chip inside it
Interfacial tension between the inwall in road is reduced by the ul-trasonic irradiation, under the increased precondition of alternate compatibility, with the Micropump
The two ends that are induced come the ultrasonic wave of mechanicalness pumping strength between interfacial tension difference its driving force for being brought
Support mutually, adjust mutually, be mutually coupled, one driving test liquid is pooled in the way of Collaboration and flows to the terminal side
To the strength of flowing；The presence of the Micropump so that its ultrasonic wave emissive porwer of the miniature ultrasonic transducer units can be allowed to appropriateness
Reduction, this is particularly suitable for for the situation containing ultrasonic wave sensitive composition in detection object；And due to the ultrasonic transducer and its
The presence of radiated ultrasonic wave, it is possible to increase alternate compatibility, reduce interfacial tension, and provide the two ends interfacial tension difference its
The special driving force brought, then, in this case, its flow resistance in the micro-channel of test liquid stream significantly drops
Low, correspondingly, its running resistance of the Micropump is greatly reduced, so, and the Micropump just can be to carry out than relatively low pumping pressure
For the pumping work of the sample solution, because mechanical pumping pressure is greatly reduced, therefore, in such a situation,
Just be not susceptible to because sample introduction terminal tool pumping pressure it is excessive caused by the sample introduction end and its near zone the micro-channel drum
Between bubble, expansion, deformation, distortion and the region substrate and cover plate the problems such as stripping etc.；This case dual drive coupling running
Scheme and add for the sample fluid flow act it is handling, can allow for using ultrasonic intensity, ultrasonic frequency,
Micropump pump power, Micropump pumping pressure etc. multiple indexs include flowing forward to be directed to the flow rate of the flowing, flowing action
Dynamic or pause flowing or acceleration flowing etc. flowing action carries out multi-parameter and accurately manipulated；By this case dual drive coupling running side
Case, is repaiied entirely without that must carry out any surface chemistry to the substrate of the dimethyl silicone polymer material its micro-channel etc. relevant surfaces
Decorations or surface chemical modification, have altogether dispensed with the laborious procedures of the surface chemical modification or surface chemical modification；On the other hand, should
The ultrasonic wave of low-power, high-frequency band, additionally it is possible to contain the large biological molecule in sample in the literalness naked poly dimethyl silicon
Absorption on its inner surface of pipeline of oxyalkyl piece, and then contain its body phase of the dimethyl silicone polymer substrate to the large biological molecule
The effect of swallowing up；The Reversible binding thing of the antigen, antibody and antigen and antibody is all to belong to described large biological molecule certainly
Type；Because described suction-operated and the described effect of swallowing up effectively are contained that therefore, dependence test result will more
Plus can objectively reflect actual conditions；The effect of the low-power, high-frequency band ultrasonic wave, also includes facilitating antigen, resists certainly
The quick of Reversible binding reaction between body is reached, and this causes dependence test operation can be with than the completion of faster speed.
As described above, the presence of the Micropump so that its ultrasonic wave emissive porwer of the miniature ultrasonic transducer units can be allowed to fit
Degree reduction, then, the feature helps to protect its sensitive coating of the working electrode, is allowed to from ultrasound injury.
Based on this case scheme, repaiied completely without the surface chemistry carried out for the dimethyl silicone polymer substrate its relevant surfaces
Decorations or surface chemical modification operation, therefore, this surface chemical modification layer or surface chemical modification layer not need to exist,
So, its body phase interior polymer molecule of the dimethyl silicone polymer substrate is constantly diffused to the surface, migrated caused by it automatically
Damaging influence to surface chemical modification layer or surface chemical modification layer is also just not present.
The technical scheme of this case has dissolved its application related one to dimethyl silicone polymer substrate addressed above totally
Row technical barrier.Based on this case scheme, the polydimethyl siloxane material of this kind very cheap and easily processing and fabricating just has can
Can in the micro-fluidic chip its prepare, production, using etc. field play bigger effect.
This case its installation position is located at the ultrasonic wave damper at the sample introduction end, from its terminal of this case micro-fluidic chip to entering
Said on the sport technique segment that ultrasonic intensity rapid decrement is realized in the such short distance in sample end, the ultrasonic wave damper its function as
The size expansion device of micro-fluidic chip, in other words, the ultrasonic wave damper its function as significantly extend it is micro-fluidic
Its terminal of chip the distance between to sample introduction end, be the equal of from length of several centimetres of the extension of script to more than ten centimetres or
Twenties centimetres of length or longer length, so so that described terminal is strong to the ultrasonic wave between sample introduction end in short distance
The sport technique segment of degree rapid decrement can relatively easily be reached, also, the size expansion device namely the ultrasonic wave damper its
Installation and removal are all very convenient, it is important that it can also be reused.
Its presence of the ultrasonic wave damper in this case device, further reduce to its pumping pressure of Micropump and pump power according to
Rely；Correspondingly, its running resistance of the Micropump is further greatly reduced, so, and the Micropump just can be with lower pumping
Pressure carries out the pumping work for the sample solution, because mechanical pumping pressure is further greatly reduced,
Therefore, in such a situation, just be less susceptible to occur because sample introduction terminal tool pumping pressure it is excessive caused by the sample introduction end and
The problems such as stripping between the micro-channel bubbling of its near zone, expansion, deformation, distortion and the region substrate and cover plate etc.；
The scheme of this case dual drive coupling running is further added for the test liquid due to its presence of the ultrasonic wave damper
The handling of flowing action is flowed, wherein, the factor that can adjust includes ultrasonic intensity, ultrasonic frequency, Micropump pump power, micro-
Pump pumps pressure, and, the selection and use of ultrasonic wave damper material, the selection of ultrasonic wave damper block size and use,
The selection of the size of its corresponding ultrasonic wave abatement ability of ultrasonic wave damper and use etc., this kind of many adjustable factor it is same
When exist, can more operation indexs, further, more it is multifactor adjustably for the flowing flow rate, stream
Action includes flow forward or pause flowing or accelerates flowing etc. flowing action to carry out the accurate manipulation under more parameters.
Its highly integrated structure of this case micro-fluidic chip, is measured the need for determining it among test application to Serum samples
Smaller, this advantageously reduces the body and mind damage of subject.
Brief description of the drawings
Fig. 1 is its rough outside side view of this case 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, 7
It is Micropump, 8 be infusion tube；Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends
Difference driving, the flow direction of its test liquid stream.The ultrasonic wave damper is depicted without in legend；Also the bullet is depicted without in legend
Power is pressed from both sides.
Embodiment
In this case that Fig. 1 is shown embodiment, the example is characterized in, the structure of the device includes micro-fluidic chip, should
The structure of micro-fluidic chip includes the substrate 1 and cover plate 2 of installing bonded to each other together, and the substrate 1 and cover plate 2 are plate
Contain the conduit via mould pressing process or etching technics formation in shape thing or tablet, that face towards the cover plate 2 of the substrate 1
Structure, substrate 1 bonded to each other being installed together has been built into the micro-fluidic chip containing pipeline configuration jointly with the cover plate 2,
The locations of structures of the pipeline is located at the substrate 1 and the cover plate 2 juncture area bonded to each other, and the two ends of the pipeline are micro- with this respectively
The sample introduction end 5 of fluidic chip and terminal 6 are connected, and the sample introduction end 5 is the injection end of the micro-fluidic chip sample solution, the end
End 6 is the terminal of sample solution flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, the terminal 6 and the sample introduction end 5
It is located remotely from each other, the distance between the terminal 6 and the sample introduction end 5 are different in the pipeline between 3 centimetres and 10 centimetres
On position in order or backward is equiped with working electrode and to electrode and reference electrode, the order refers to the reference electricity
Extremely locations of structures closer to the position of terminal 6, the backward refer to the reference electrode locations of structures closer to it is described enter
The position of sample end 5, the working electrode is resisted by conductive electrode and the tumor markers that embedded being attached on the conductive electrode
The gold size sensitive membrane of body is constituted, and parallel construction is presented in the construction of the pipeline, and the pipeline in parallel construction is by eight laterals
Parallel connection is constituted, and its appearance profile of the pipeline of the presentation parallel construction is similar to the profile of parallel circuit, the working electrode
Quantity be eight, the installation positions of eight working electrodes is located in eight laterals respectively, and, eight works
The tumor markers antibody made in the sensitive membrane structure of its top layer gold size of electrode is that tumor markers antigen can be specifically bound respectively
Eight kinds of tumor markers antibody materials, eight kinds of antibody materials be respectively tumor markers antibody CA199, CA153, CA125,
CA242, AFP, CEA, EB and β-HCG, the antigen are the antigen of broad sense, and the antibody is the antibody of broad sense, described
Its material of working electrode is argent material, gold material, carbon material or thermal decomposition conducting polymer material, the work electricity
Extremely column, sheet or thread is presented in pattern, and its material of the substrate 1 is dimethyl silicone polymer material, its surface of substrate 1
The surface of primary form, the surface of the primary form its be intended to refer to not pass through any surface chemical modification or any surface
The surface of the primary form of the material of chemical modification, the structure of the device also includes miniature ultrasonic transducer units 4, and, it is high
Frequency vibration swings electric signal transmission cable 3, and one end of the higher-order of oscillation electric signal transmission cable 3 connects with the miniature ultrasonic transducer units 4
It is connected together, the miniature ultrasonic transducer units 4 are installed in described in the cover plate 2 of the micro-fluidic chip or the neighbouring of substrate 1 with attaching
The position of terminal 6；Its major function of the miniature ultrasonic transducer units 4 is, in the actual sample introduction test of micro-fluidic chip, to utilize it
The ultrasonic wave launched reduces the interfacial tension between sample solution and the inwall of its inner passage of micro-fluidic chip, can
It is enough compatible, also, using between the sample introduction end 5 and the terminal 6 and the installation position of miniature ultrasonic transducer units 4
Difference in distance difference and its ultrasonic intensity experienced, its interfacial tension of sample introduction end 5 described in induced synthesis with it is described
Interfacial tension difference between difference between its interfacial tension of terminal 6, the micro-fluidic chip two ends 5,6 can be in the miniflow
Pressure gap is formed between the two ends 5,6 for controlling chip, the pressure gap can drive sample solution to be flowed to the direction of terminal 6
It is dynamic；Its function of the miniature ultrasonic transducer units 4 also includes checking big point of biology contained in sample with its ultrasonic wave launched
Its absorption on the micro-fluidic chip its inner passage inner surface of son, and then check the substrate 1 of the dimethyl silicone polymer material
Swallow up effect of its body phase to the large biological molecule；It is soft and have the substrate 1 of the dimethyl silicone polymer material of elasticity its function
Including with its property to the strong absorption of ultrasonic wave, being absorbed strongly to ultrasonic wave, and thereby in the micro-fluidic chip terminal
6 to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 5；And, Micropump 7, this is micro-
Pump 7 is connected with the sample introduction end 5；The function of the Micropump 7 is, in the sample solution and its inner passage of the micro-fluidic chip
Interfacial tension between wall is reduced by the ul-trasonic irradiation, under the increased precondition of alternate compatibility, with the machine of the Micropump 7
Its driving force for being brought of interfacial tension difference between the two ends 5,6 that are induced come the ultrasonic wave of tool pumping strength
Support mutually, adjust mutually, be mutually coupled, one driving test liquid is pooled in the way of Collaboration and flows to the terminal 6
The strength of direction flowing；Its thickness of the cover plate 2 and substrate 1 is between 1.0 millimeters and 5.0 millimeters；And, ultrasound
Ripple damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；Its material of the ultrasonic wave damper be microcellular rubber,
Sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, the inner side of each clamping limb
Face is relative with the medial surface of another clamping limb, and the medial surface of one of clamping limb is close to the sample introduction end 5 of the micro-fluidic chip,
The medial surface of another clamping limb is close to the ultrasonic wave damper, the elastic clip entering the micro-fluidic chip with its gripping strength
Sample end 5 and the ultrasonic wave damper are clipped together bonded to each otherly, the ultrasonic wave damper with its material brought to ultrasonic wave
Strong consumption, further support the limited short distance arrived between the sample introduction end 5 in the micro-fluidic chip terminal 6 it
The rapid decrement of ultrasonic intensity is inside realized, and thereby further expands described its interfacial tension of sample introduction end 5 and the terminal 6
Difference between its interfacial tension.
The ultrasonic wave damper is depicted without in legend；Also the elastic clip is depicted without in legend.
Arrow in legend indicate the micro-fluidic chip its in actual motion, by two ends 5,6 pressure differentials 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.
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；It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；It can also be customized to relevant manufacturers.
Micropump 7 can be customized to specialized factory involved by legend.
Its connected mode with various micro-fluidic chip of various Micropump is known.
Its inner passage of the micro-fluidic chip involved by this case is the pipeline of hydrophobic capillary form.
The Micropump both can be the Micropump of external form；The Micropump can also be done into or say inside the embedded micro-fluidic chip
The Micropump of the built in version of its sample introduction end structure position or the sample introduction end Near-neighbor Structure position, its basic structure key element and external form
Micropump it is identical.Micropump in legend is the Micropump of external form.
Each working electrode in this example structure and electrode and reference electrode via each special cable or can be said respectively
Get lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as annex or saying interface connection of getting lines crossed.
In view of this case pipeline of the presentation parallel construction its form that related text expresses that it is described above is clear enough
It is clear, the concrete form of the pipeline in this kind of micro-fluidic chip of this case is no longer specifically illustrating in this case embodiment.
Antibody described in this case refers to the antibody of broad sense；Antigen described in this case refers to the antigen of broad sense；It is immunized described in this case multiple
Compound refers to the immune complex of broad sense.
Claims (10)
1. more than type of drive coupling running female tumor mark joint inspection chip apparatus, it is characterised in that the structure of the device
Including micro-fluidic chip, the structure of the micro-fluidic chip includes the substrate and cover plate of installing bonded to each other together, the substrate and
Cover plate is plate object or tablet, and that face towards the cover plate of the substrate is contained to be formed via mould pressing process or etching technics
Channel structure, substrate bonded to each other being installed together and the cover plate have been built into the micro-fluidic core containing pipeline configuration jointly
Piece, the locations of structures of the pipeline is located at the substrate and cover plate juncture area bonded to each other, and the two ends of the pipeline are micro- with this respectively
The sample introduction end of fluidic chip and terminal connection, the sample introduction end is the injection end of the micro-fluidic chip sample solution, and the terminal is this
The terminal that sample solution flows in its chip when the actual sample introduction of micro-fluidic chip is tested, the terminal is located remotely from each other with the sample introduction end, should
The distance between terminal and the sample introduction end are in order or inverse on diverse location in the pipeline between 3 centimetres and 10 centimetres
Sequence is equiped with working electrode and to electrode and reference electrode, and the order refers to that its locations of structures of the reference electrode is more leaned on
The nearly terminal location, the backward refers to the reference electrode locations of structures closer to the sample introduction end position, the work
Electrode is made up of conductive electrode and the gold size sensitive membrane for having embedded tumor markers antibody being attached on the conductive electrode,
Parallel construction is presented in the construction of the pipeline, and the pipeline in parallel construction is made up of eight lateral parallel connections, and the presentation is simultaneously
Its appearance profile of the pipeline of connection construction is similar to the profile of parallel circuit, and the quantity of the working electrode is eight, this eight
The installation position of working electrode is located in eight laterals respectively, and, its top layer gold size of eight working electrodes is sensitive
Tumor markers antibody in membrane structure is the eight kinds of tumor markers antibody that can be specifically bound to tumor markers antigen respectively
Material, eight kinds of antibody materials are tumor markers antibody CA199, CA153, CA125, CA242, AFP, CEA, EB respectively
And β-HCG, the antigen is the antigen of broad sense, and the antibody is the antibody of broad sense, and its material of the working electrode is metal
Column, piece is presented in silver-colored material, gold material, carbon material or thermal decomposition conducting polymer material, its pattern of the working electrode
Shape is thread, and its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, and this is primary
The surface of form its be intended to refer to the primary of the material not no by any surface chemical modification or any surface chemical modification
The surface of form, the structure of the device also includes miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable should
One end of higher-order of oscillation electric signal transmission cable links together with the miniature ultrasonic transducer units, miniature ultrasonic transducer units patch
The position of the cover plate of the micro-fluidic chip or the neighbouring terminal of substrate is installed in attachedly；Its is main for the miniature ultrasonic transducer units
Function is that in the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it reduces sample solution and the micro-fluidic core
Interfacial tension between the inwall of its inner passage of piece, can be compatible, also, utilizes the sample introduction end and the terminal
Difference with the distance between miniature ultrasonic transducer units installation position difference and its ultrasonic intensity experienced, is lured
Lead between the difference to be formed between described its interfacial tension of sample introduction end and the terminal its interfacial tension, the micro-fluidic chip two ends
Interfacial tension difference can form pressure gap between the two ends of the micro-fluidic chip, the pressure gap can drive sample solution
To the end flow；Its function of the miniature ultrasonic transducer units is also contained in sample including being checked with its ultrasonic wave launched
Large biological molecule its absorption on the micro-fluidic chip its inner passage inner surface, and then check the dimethyl silicone polymer material
Swallow up effect of its body phase of the substrate of matter to the large biological molecule；The substrate of the dimethyl silicone polymer material that is soft and having elasticity
Its function includes, with its property to the strong absorption of ultrasonic wave, ultrasonic wave being absorbed strongly, and thereby in the micro-fluidic chip
The terminal is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end；And, Micropump, this is micro-
Pump is connected with the sample introduction end；The function of the Micropump is, between the inwall of the sample solution and its inner passage of micro-fluidic chip
Interfacial tension reduced by the ul-trasonic irradiation, under the increased precondition of alternate compatibility, pumped with the mechanicalness of the Micropump
Interfacial tension difference its driving force brought between the two ends that strength induces come the ultrasonic wave is supported mutually, mutually
Adjust, be mutually coupled, the strength that one driving test liquid flows to the terminal direction flowing is pooled in the way of Collaboration；
Described its thickness of cover plate and substrate is between 1.0 millimeters and 5.0 millimeters；And, ultrasonic wave damper, the ultrasonic wave disappears
Subtract its profile of device in block, tabular or bar-shaped；Its material of the ultrasonic wave damper is that microcellular rubber, sponge rubber or polyurethane are micro-
Hole elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, medial surface and another clamping limb of each clamping limb
Medial surface is relative, and the medial surface of one of clamping limb is close to the sample introduction end of the micro-fluidic chip, the inner side of another clamping limb
The ultrasonic wave damper is close in face, and the elastic clip is cut down the sample introduction end of the micro-fluidic chip and the ultrasonic wave with its gripping strength
Device is clipped together bonded to each otherly, the strong consumption to ultrasonic wave that the ultrasonic wave damper is brought with its material, enters one
Step is supported to realize the quick of ultrasonic intensity within micro-fluidic chip terminal to the limited short distance between the sample introduction end
Successively decrease, and thereby further expand the difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension.
2. the female tumor mark joint inspection chip apparatus of many type of drive coupling runnings according to claim 1, it is special
Levy and be, it is capillary channel that the pipeline, which includes the lateral,.
3. the female tumor mark joint inspection chip apparatus of many type of drive coupling runnings according to claim 1, it is special
Levy and be, the thermal decomposition conducting polymer be by polyimides or polyacrylonitrile be heat-treated through anoxybiotic after the electric conductivity material that is formed
Material.
4. the female tumor mark joint inspection chip apparatus of many type of drive coupling runnings according to claim 1, it is special
Levy and be, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the working electrode
Length between 1 micron to 15000 microns.
5. the female tumor mark joint inspection chip apparatus of many type of drive coupling runnings according to claim 1, it is special
Levy and be, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. the female tumor mark joint inspection chip apparatus of many type of drive coupling runnings according to claim 1, it is special
Levy and be, its material of the cover plate in structure is dimethyl silicone polymer material.
7. the female tumor mark joint inspection chip apparatus of many type of drive coupling runnings according to claim 1, it is special
Levy and be, the Micropump is miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.
8. the female tumor mark joint inspection chip apparatus of many type of drive coupling runnings according to claim 1, it is special
Levy and be, the microcellular rubber is micropore silicon rubber or micropore fluorubber.
9. the female tumor mark joint inspection chip apparatus of many type of drive coupling runnings according to claim 1, it is special
Levy and be, the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission cable
Its other end is connected with the higher-order of oscillation electric signal generator.
10. the female tumor mark joint inspection chip apparatus of many type of drive coupling runnings according to claim 1, it is special
Levy and be, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 2 milliwatts and 2000 milliwatts, and this is miniature
The frequency of its ultrasonic wave operationally launched of ultrasonic transducer is between 100KHz and 12MHz.
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| CN201610223190.2A CN107282145A (en) | 2016-04-01 | 2016-04-01 | The female tumor mark joint inspection chip apparatus of many type of drive coupling runnings |
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| CN201610223190.2A CN107282145A (en) | 2016-04-01 | 2016-04-01 | The female tumor mark joint inspection chip apparatus of many type of drive coupling runnings |
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