CN107694642A - Classifiable tumor mark joint inspection chip apparatus suitable for male's physical examination examination - Google Patents
Classifiable tumor mark joint inspection chip apparatus suitable for male's physical examination examination Download PDFInfo
- Publication number
- CN107694642A CN107694642A CN201610703590.3A CN201610703590A CN107694642A CN 107694642 A CN107694642 A CN 107694642A CN 201610703590 A CN201610703590 A CN 201610703590A CN 107694642 A CN107694642 A CN 107694642A
- Authority
- CN
- China
- Prior art keywords
- micro
- terminal
- substrate
- fluidic chip
- male
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
- B01L3/50273—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
-
- 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
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
-
- 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
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
-
- 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
- B01L2300/12—Specific details about materials
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
- B01L2400/0439—Moving fluids with specific forces or mechanical means specific forces vibrational forces ultrasonic vibrations, vibrating piezo elements
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Clinical Laboratory Science (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Cell Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
Abstract
The present invention relates to a kind of classifiable tumor mark joint inspection chip apparatus suitable for male's physical examination examination, belong to analysis testing field.Dimethyl silicone polymer be PDMS its be used for making the substrates of seven kinds of classifiable tumor markers in detecting micro-fluidic chips of male, have many advantages, but there is also serial problem;This case is directed to the serial problem.This case main points are, the selected PDMS with ecosystem surface of substrate, and the chain ring type magnetic holding device for being equiped with miniature ultrasonic transducer units socket is positioned at the sample liquid stream terminal of the micro-fluidic chip its neighbor positions, interfacial tension is reduced with ultrasonic wave, strong absorbability using PDMS to ultrasonic wave simultaneously, reach ultrasonic intensity rapid decrement in short distance, so as to form interfacial tension difference at the both ends of the chip, the difference provides a kind of strength driven sample liquid stream and flowed along hydrophobic capillary channel to the terminal direction, the strength while with Micropump its mechanicalness pumping strength Collaboration for being included in structure.
Description
Technical field
The present invention relates to a kind of classifiable tumor mark joint inspection chip apparatus suitable for male's physical examination examination, belong to analysis
Testing field.
Background technology
Tumor markers (tumor marker, TM) refers in the generation and breeding of tumour, by tumour cell sheet
Either tumour cell is reacted and caused, a kind of material of the presence of reflection tumour and growth by body caused by body, bag
Include protein, hormone, enzyme (isodynamic enzyme) and oncoprotein etc..The tumor markers in blood samples of patients or body fluid is chemically examined, can be
Early detection tumour in cancer screening, and the effect of observe oncotherapy and judge patient's prognosis.Clinically commonly use at present
Tumor markers has:(1) alpha-fetoprotein (AFP) is the mark of the tumours such as primary carcinoma of liver, carcinoma of testis, oophoroma;(2) cancer embryo
Antigen (CEA) is the mark of the tumours such as digestive system tumor, lung cancer, breast cancer;(3) CA125 (CA125) is ovary
The mark of the tumours such as cancer;(4) CA153 (CA153) is the mark of the tumours such as breast cancer;(5) CA19-9
(CA19-9) it is the mark of digestive system tumor;(6) CA724 (CA724) is the mark of the tumours such as stomach cancer, oophoroma
Thing;(7) carbohydrate antigen 242 (CA242) is the mark of digestive system tumor;(8) CA50 (CA50) is digestive system
The mark of the tumours such as tumour, breast cancer, lung cancer;(9) CYFRA21-1 (Cy211) is the mark of the tumours such as non-small cell lung cancer;
(10) neuronspecific enolase (NSE) is the mark of the tumours such as ED-SCLC, neuroendocrine tumor;(11) before
Row gland specific antigen (PSA) is the tumor markers of prostate cancer;(12) human chorionic gonadotrophin (HCG) is that embryo is thin
The mark of the tumours such as born of the same parents' cancer, trophoblastic tumor (suede cancer, vesicular mole);(13) thyroglobulin (TG) is the mark of thyroid cancer
Will thing;(14) ferritin (SF) is the mark of the tumours such as digestive system tumor, liver cancer, breast cancer, lung cancer;(15) β 2- microballoons
Albumen (β 2-MG) is in patient body fluids such as chronic lymphocytic leukemia, lymthoma, myeloma, lung cancer, thyroid cancer, nasopharyngeal carcinoma
Middle rise;(16) squamous cell antigen (SCC) is the tumor markerses such as cervical carcinoma, lung squamous cancer, the cancer of the esophagus.Clinically detect at present
The tumor markers overwhelming majority be not only present in malignant tumour, exist in benign tumour, even embryonic tissue, normal group
In knitting.Therefore, tumor markers has dynamic chek and multinomial joint inspection more valuable.So for numerous tumor-markers
Thing, clinically how to selectDifferent tumours understands some relatively special tumor markerses, as CA153 often appears in mammary gland
Cancer;CEA often appears in intestinal cancer, stomach cancer;CA19-9 often appears in intestinal cancer, cancer of pancreas;CA125 often appears in oophoroma etc..Face
Bed doctor can be according to the different mark of different tumor examinations.Same tumour or different types of tumour can have a kind of or several
Kind tumor markers is abnormal;Same tumor markers can occur in different tumours.To improve the auxiliary of tumor markers
Which kind of mark can carry out tumor markers joint-detection to diagnostic value as the follow-up visit monitoring index after treatment with determination,
The complementary tumor markers composition best of breed of several sensitivity of reasonable selection, specific performance, carries out joint-detection.In general
The joint-detection of tumor markers can improve the accuracy to diagnosing tumor.
Only with regard to Diagnostic Value of Several Serum Tumor Markers its joint-detection background of related itself general picture or overview for, can be with
Referring to following Chinese invention patent application case:CN200410041175.3、CN200510026780.8、
CN200610040051.2、CN200910064647.X。
Only for the microfluidic chip technology overall general picture of itself, it is first to may refer to famous micro-fluidic expert Lin Ping Cheng
The raw monograph " diagram Microfluid based Lab on a chip " gone out not long ago, the monograph is published via Science Press, the monograph for
Past of microflow control technique, now, and, vision of the future etc. etc., suffer from detail, be deep into the treatise of detail
Discuss.
So, the focal issue that this case that to have a talk below is paid special attention to.
The basic framework of micro-fluidic chip, including be etched with the substrate of small fluid course and fit together therewith
Cover plate, the small fluid course on the substrate, before upper cover plate is assembled, it is apparent on see to be exactly some micro-channels, to wait until
After covering cover plate thereon, just really closure forms the small fluid course, the conduit inner surface of the micro-channel together with
The part cover plate that surround the micro-channel forms described small fluid course together;So, it is clear that after assembling completes
The small fluid course, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, should
The state or property of micro-channel inner surface substantially determine the integrality or property of the small fluid course;Therefore say, this
The inner surface state or inner surface property of micro-channel of the individual structure on substrate are key factors;In principle, it is any can
The material of its solid forms is kept or kept substantially, can be used to make substrate and cover plate, such as, it can act as substrate and lid
The material of piece can be monocrystalline silicon piece, quartz plate, sheet glass, high polymer for example dimethyl silicone polymer, polymethyl methacrylate,
Makrolon etc.;Certainly, the selection of substrate and the selection of cover plate be able to can also be differed with identical;From material consumption, make
From the point of view of difficulty and application popularization prospect etc. etc., not small difference, the especially choosing of that substrate between these materials be present
Material, 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 micro-channel is made on the substrate of sample, and the lower cost for material, base is made with the polydimethyl siloxane material
Piece, micro-channel, and the cover plate phase made with the cheap material such as glass or polypropylene or other plastic sheets are being suppressed or etched thereon
Coordinate, be a kind of more satisfactory selection seemingly;Certainly, patch material can also select to use cheap dimethyl silicone polymer
Material:So, this substrate selection is the scheme of polydimethyl siloxane material, and material is extremely cheap, and making is extremely simple, seems
It should be extremely easy to popularize, promote.
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, micro-channel is built on this material, if without being operated for the modified of the micro-channel surface, that
, after overall assembling is completed, that is, after covering cover plate, because the micro-channel its inner surface in structure occupies most liquid
The inner surface of circulation road, then, its strong hydrophobic property of the PDMS micro-channels inner surface, is deciding factor, it can cause
Similar to the aqueous solution the fine liquid stream of polar liquid by becoming very difficult, its flow resistance is big, or even in general is micro-
Pump is all 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 behaviour
Make;So, this is pretty troublesome for the modified operation of PDMS micro-channel inner surfacesThat falls nor this problem, is formed tight
Weight technology puzzlement, be another problem:PDMS polymer molecules inside its body phase of this PDMS material substrate have automatic
The characteristic diffuse to the surface, migrated, the spy that this substrate body phase inside PDMS polymer molecules are diffused to the surface, migrated automatically
Property, the state after modification by its inner surface of that micro-channel of surface modifying and decorating will be caused can not to maintain long enough
Time, the holding time for micro-channel its inner surface state after that is surface-modified be substantially only sufficient to complete laboratory internal
The time of test experiments needs;In other words, by surface modification or the PDMS micro-channel inner surfaces of surface modification, it is modified
The surface state that is formed can not be lasting afterwards or after saying modification, but soon automatically tends to or say and become surface modification again
Surface state before, the strong hydrophobic surface state of that script is returned in the shorter time, then, just think, this
The micro-fluidic chip of sample can largely make, mass storage, be widely popularized, and answer is it is obvious that is, impossible.This
Micro-channel on PDMS material, if not doing surface modification, similar to the aqueous solution the fine liquid stream of polar solvent can not pump it is logical
Cross, chip also cannot just use;And if having done surface modification, its state after modifying can not be persistently kept again, or together
Sample can not popularization and application.
So, how to accomplish that substrate can either be made using cheap PDMS material, and the microflute can be released
Road inner surface decorating state can not persistently, chip can not largely make, largely lay in and then be widely popularized and such a make ability
The puzzlement that the numerous professionals in domain 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 micro-channels inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is person in charge of reception at ceremonies
Phenomenon existing for sight.
, 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 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
Swallowed up by PDMS substrate body phases;But or that old problem, that is, the chemical modification on PDMS material surface is modified
Surface state afterwards can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface, move automatically
The process of shifting, it 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 bases
Its micro-channel inner surface of piece 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 micro-channel inner surfaces to large biological molecule for a long time, and then prevent PDMS substrate body phases
The effect of swallowing up to large biological molecule so that related chip manufactured goods be able to maintain that one it is prolonged enough, reasonably guarantee the quality
Phase, it is exactly a very intractable problem.The problem equally makes this area numerous as another problem addressed above
Professional is entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise.
Also be present many year in the problem, 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 surface
Chemical modification is difficult to persistently again, therefore, actually can only still belong to effective in the surface state after the modification of its surface or surface modification
It is short-term within use it;If having had been subjected to that ofer short duration period of validity, and still by force if use, due to table
Again close to hydrophobic state, bigger flowing is then already certainly existed using usual Micropump driving sample liquid stream for surface state
Resistance, so, just by increasing Micropump pump power and pumping pressure test liquid can only be forced to flow to target direction flowing, as above
Described, this PDMS material is soft, pumps sample liquid stream with too high, mechanical pumping pressure, will cause the substrate
Bubbling, expanded, distortion, deformation, also, this high pressure feelings occur for the micro-channel that its sample introduction end includes sample introduction end near zone
Under condition, the stripping between substrate and cover plate also easily occurs in the sample introduction end and its micro-channel of near zone and its periphery,
Under this situation, the crack for the appearance that sample solution will enter after the stripping between the substrate and cover plate formed and it is horizontal everywhere
Stream, this actually results in the damage of the micro-fluidic chip;It is certainly, not in place if surface modification or surface modification script,
It can cause said circumstances occur within the of short duration usual term of validity;The feelings of liquid stream driving are being carried out using additional Micropump merely
Under condition, the above-mentioned problem exists all the time.As described above, if any surface modification or surface modification etc. were not done completely
Pre action, then, the above-mentioned problem will be even more serious, is roused even without micro-channel described in sample introduction end and its near zone occurs
The problems such as being peeled off between bubble, expanded, distortion, deformation and substrate and cover plate, merely because the flow resistance is excessive, using high pressure
Micropump also may not can drive sample liquid stream to be marched forward towards terminal side.
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
Three aspect a series of problem actually mutually involved together, also, by the solution be applied to structure one
New being directed to of kind belongs to seven kinds that male's physical examination especially need to pay close attention to and carried out together than more typical primary tumor mark
When examination and meanwhile detection micro flow control chip device.
The present invention solves the technical problem by following scheme, and the device that the program provides is that one kind is suitable to male's physical examination
The classifiable tumor mark joint inspection chip apparatus of examination, program feature are that the structure of the device includes micro-fluidic chip, should
The structure of micro-fluidic chip includes being bonded to each other installing substrate and cover plate together, the substrate and cover plate be plate object or
The channel structure via mould pressing process or etching technics formation, phase are contained in tablet, that face towards the cover plate of the substrate
The substrate being mutually jointly mounted to together has been built into the micro-fluidic chip containing pipeline configuration jointly with the cover plate, the pipeline
Locations of structures is located at the juncture area that the substrate and the cover plate are bonded to each other, the both ends of the pipeline respectively with the micro-fluidic chip
Sample introduction end and terminal connection, the sample introduction end is the injection end of the micro-fluidic chip sample solution, and the terminal is the micro-fluidic core
During the test of piece actual sample introduction in its chip sample solution flowing terminal, the terminal is located remotely from each other with the sample introduction end, the terminal and
Between 3 centimetres and 10 centimetres, the terminal links together with terminal liquid pool at the distance between the sample introduction end, the terminal liquid pool
The profile of its structure is in pond shape, pit shape or cup-shaped, and the terminal liquid pool is used to receive the sample for flowing to terminal via the pipeline
Solution, in the pipeline on diverse location in order or backward is equiped with working electrode and to electrode and reference electrode, institute
State order and refer to its locations of structures of the reference electrode closer to the terminal location, the backward refers to the reference electricity
For pole locations of structures closer to the sample introduction end position, the working electrode is by conductive electrode and is attached to the conductive electrode
On the gold size sensitive membrane for having embedded tumor markers antibody form, parallel construction is presented in the construction of the pipeline, described in parallel connection
The pipeline of construction is made up of seven lateral parallel connections, and its appearance profile of the pipeline of the presentation parallel construction is similar to simultaneously
Join the profile of circuit, the quantity of the working electrode is seven, and the installation position of seven working electrodes is located at described seven respectively
In bar lateral, and, the tumor markers antibody in its top layer gold size sensitivity membrane structure of seven working electrodes is respectively
The seven kinds of tumor markers antibody materials that can be specifically bound to tumor markers antigen, seven kinds of antibody materials are tumour respectively
Mark antibody CA199, CA242, AFP, EB, CEA, TPSA and FPSA, the antigen are the antigen of broad sense, and the antibody is
The antibody of broad sense, its material of the working electrode are argent material, gold material, carbon material or thermal decomposition conducting polymer
Column, sheet or thread is presented in material, its pattern of the working electrode, and its material of the substrate is dimethyl silicone polymer material,
Its surface of the substrate is the surface of primary form, the surface of the primary form its be intended to refer to and do not pass through any surface chemistry
The surface of the primary form of the material of modification or any surface chemical modification, the structure of the device also include chain ring type electromagnetic clamp
Tool, six links is shared in its structure of the chain ring type magnetic holding device, the link is in strip, shaft-like or bar-shaped, each adjacent ring
Section is hinged to form chain link, the hexagonal cyclic structure of its appearance profile of the chain link, each top of the hexagonal annular structure
Its locations of structures of angle is articulated structure position, and two therein of the hexagonal annular structure is in its material of the link of opposite side position
Matter is magnetic conductivity material, and its material of the remaining four processes of the hexagonal annular structure is non-magnetic material, described non magnetic
Material refers to the material not responded strongly to externally-applied magnetic field, in a link among two links of the magnetic conductivity material
Magnet exciting coil is wound with, the link for being wound with magnet exciting coil is respectively equiped with one in the both sides neighbor positions of its magnet exciting coil
The pole shoe of magnetic conductivity material, two pole shoes are shared, two pole shoes are directed to the link of another magnetic conductivity material, and this is another
Attach to fix on its surface of the link of one magnetic conductivity material and be equiped with miniature ultrasonic transducer units, rely on electromagnetism adhesive strength
The chain ring type magnetic holding device is socketed the close position for being positioned at its terminal of the micro-fluidic chip, and, higher-order of oscillation telecommunication
Number transmission cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable link together;The chain
Ring type magnetic holding device provides a function of facilitating the device to disassemble;Its major function of the miniature ultrasonic transducer units is micro-
During the test of fluidic chip actual sample introduction, the ultrasonic wave launched using it reduces sample solution and the micro-fluidic chip inside it
Interfacial tension between the inwall of passage, can be compatible, also, miniature with this using the sample introduction end and the terminal
Difference in the distance between ultrasonic transducer installation position difference and its ultrasonic intensity experienced, induced synthesis
Difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension, the boundary between the micro-fluidic chip both ends
Face tension difference can form pressure gap between the both ends of the micro-fluidic chip, the pressure gap can drive sample solution to
The end flow;The ultrasonic wave that its function of the miniature ultrasonic transducer units also includes being launched with it is checked contained in sample
Large biological molecule its absorption on the micro-fluidic chip its inner passage inner surface, and then check the dimethyl silicone polymer
Swallow up effect of its body phase of the substrate of material to the large biological molecule;The dimethyl silicone polymer material that is soft and having elasticity
Its function of substrate includes, with its property to the strong absorption of ultrasonic wave, absorbing ultrasonic wave strongly, and thereby in the miniflow
Control chip terminal is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end;It is and micro-
Pump, the Micropump are connected with the sample introduction end;The function of the Micropump is, in the sample solution and its inner passage of micro-fluidic chip
Interfacial tension between inwall is reduced, under the increased precondition of alternate compatibility by the ul-trasonic irradiation, with the Micropump
Interfacial tension difference its caused driving force that mechanicalness pumping strength is come between the both ends of ultrasonic wave induction
Support mutually, adjust mutually, be mutually coupled, one driving test liquid is pooled in a manner of Collaboration and flows to the terminal side
To the strength of flowing, some high hydroscopic resin particles are filled with the terminal liquid pool, its opening end of terminal liquid pool is by ventilative micro-
Pore membrane 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.
The tumor markers antibody is the antibody of broad sense, and the antibody of the broad sense refers to possessing antibody function or functionally
Can occur to combine with tumor markers involved by various corresponding clinics and form immune complex or exempt from similar to antibody
The material of the analog of epidemic disease compound;The tumor markers antigen is the antigen of broad sense, and the antigen of the broad sense refers to can
Using corresponding antibodies or the material for being functionally similar to antibody need to differentiate, detect involved by the various clinics of enzyme mark detection
Tumor markers.
The word of magnet exciting coil one art-recognized meanings of itself are known.
The word of magnetic conductivity material one art-recognized meanings of itself are known;The material for belonging to magnetic conductivity material is for example pure
Iron, silicon steel, soft magnetic ferrite etc..
Non magnetic material described in this case refers to the material not responded strongly to externally-applied magnetic field, belongs to the non magnetic material
The material of matter such as metallic copper, metallic zinc, ormolu, metallic aluminium, almag etc..
The be hinged word art-recognized meanings of itself field in Machine Design is known.
The word of Micropump one art-recognized meanings of itself are known for the professional in micro-fluidic chip field.
The Micropump both can be the Micropump of external form;The Micropump can also 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 micro-channel molding or lithographic technique for, be open-and-shut known skill
Art.
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 drives liquid stream in the hydrophobic capillary of seven channel microfluidic chip with dual drive coupling operating mode
Flowed in passage, joint-detection is carried out to seven kinds of tumor markers antigens respectively using multi-channel electrochemical analyzer device.
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 its close position relies on electromagnetism adhesive strength set in the terminal of the micro-fluidic chip
The described chain ring type magnetic holding device of positioning is connect, is installed with institute's attaching in the chain ring type magnetic holding device one magnetic conductivity link micro-
Type ultrasonic transducer, the low-power launched using it, the ultrasonic wave of high-frequency band so that without surface chemical modification or
It is compatible between strong hydrophobic its tube wall of micro-fluidic chip internal pipeline and the test object aqueous solution of surface chemical modification
Property be significantly increased, this is sample liquid stream by providing a realistic possibility;Meanwhile utilize dimethyl silicone polymer substrate
Its strong absorbability to ultrasonic wave, in shorter distance, it is, from the terminal to the sample introduction end
In the very short distance of only several centimeters yardsticks, reach the rapid decrement of ultrasonic intensity, thereby described in the micro-fluidic chip
The difference of the interfacial tension is caused at both ends, and the difference of the interfacial tension between the both ends can cause a kind of driving force, this kind
Its function of driving force is to drive sample liquid stream in strong hydrophobic capillary channel originally caused by interfacial tension difference
The introversive terminal direction flowing;And the simultaneous Micropump in structure, its function are, in the sample solution and the miniflow
Interfacial tension between the inwall of its inner passage of control chip is reduced, the increased premise of alternate compatibility by the ul-trasonic irradiation
Under the conditions of, the interfacial tension difference come between the both ends of ultrasonic wave induction with the mechanicalness of Micropump pumping strength its
Caused driving force is supported mutually, adjusts mutually, is mutually coupled, and one driving sample is pooled in a manner of Collaboration
The strength that liquid stream flows to the terminal direction;The presence of the Micropump so that the miniature ultrasonic transducer units its ultrasonic wave transmitting
Intensity can be allowed to appropriate reduction, and this is particularly suitable for for the situation containing ultrasonic wave sensitive composition in detection object;And by
In the presence of the ultrasonic transducer and its radiated ultrasonic wave, it is possible to increase alternate compatibility, reduce interfacial tension, and provide
The both ends interfacial tension difference special driving force caused by it, then, in this case, sample liquid stream its in the microflute
Flow resistance in road is greatly reduced, and correspondingly, its running resistance of the Micropump is greatly reduced, so, the Micropump just can with than
Relatively low pumping pressure carries out the pumping work for the sample solution, because mechanical pumping pressure is greatly reduced,
Therefore, in such a situation, be just not susceptible to caused by sample introduction terminal tool pumping pressure is excessive the sample introduction end and
Peel off etc. and to ask between the micro-channel bubbling of its near zone, expansion, deformation, distortion and the region substrate and cover plate
Topic;This case dual drive couples the scheme of running and adds handling, the Neng Gouyun for sample fluid flow action
Perhaps pressure etc. multiple indexs are pumped to be directed to the flowing using ultrasonic intensity, ultrasonic frequency, Micropump pump power, Micropump
Flow rate, flowing action include flow forward or pause flowing or accelerate flowing etc. flowing action progress multi-parameter it is accurate
Manipulation;By the scheme of this case dual drive coupling running, entirely without must its be micro- to the substrate of the dimethyl silicone polymer material
Conduit etc. relevant surfaces carry out any surface chemical modification or surface chemical modification, have altogether dispensed with the surface chemical modification
Or the laborious procedures of surface chemical modification;On the other hand, the ultrasonic wave of the low-power, high-frequency band, additionally it is possible to contain in sample
Absorption of the large biological molecule on literalness naked its inner surface of pipeline of dimethyl silicone polymer substrate, and then contain should
Swallow up effect of its body phase of dimethyl silicone polymer substrate to the large biological molecule;The antigen, antibody and antigen are with resisting
The Reversible binding thing of body is all the type for belonging to described large biological molecule certainly;Due to described suction-operated and described
The effect of swallowing up effectively is contained that therefore, dependence test result will be better able to objectively reflect actual conditions;The low-power,
The effect of high-frequency band ultrasonic wave, also include facilitating what the Reversible binding between antigen, antibody react quickly to reach certainly, this makes
Obtaining 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 permitted
Perhaps appropriateness reduces, then, the feature helps to protect its sensitive coating of the working electrode, is allowed to from ultrasound injury.
Based on this case scheme, completely without carrying out coming to the surface for its relevant surfaces of dimethyl silicone polymer substrate
Modification or surface chemical modification operation are learned, therefore, this surface chemical modification layer or surface chemical modification layer not need
In the presence of, then, its body phase interior polymer molecule of the dimethyl silicone polymer substrate constantly diffuses to the surface, migrates its institute automatically
It is caused that the damaging influence of the surface chemical modification layer or surface chemical modification layer is also just not present.
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.
Attached in the chain ring type magnetic holding device one magnetic conductivity link in this case structure it is fixed installed it is described miniature
Ultrasonic transducer, this architecture provides a function of facilitating the device to disassemble, in this way, the chain ring type magnetic holding device is together with it
The miniature ultrasonic transducer units attached in one magnetic conductivity link just easily can be mutually disengaged with the micro-fluidic chip,
So, the component that the part can freely depart from is reused many times in which just can circulate benignly;The architectural feature is advantageous to save
The about 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 be this case device chain ring type magnetic holding device its with appearance side rough under the micro-fluidic chip socket state
View, the legend and indicates the relative position relation under the socket state between each component.
Fig. 2 is the outside side view under another viewing angle of this case device;Fig. 2 viewing angle and Fig. 1's
Viewing angle is mutually perpendicular to;The components such as infusion tube and Micropump are depicted without in Fig. 2.
In figure, 1 is chain ring type magnetic holding device, and 2 be the terminal of the micro-fluidic chip, and 3 be the institute of the micro-fluidic chip
Sample introduction end is stated, 4 be the substrate of dimethyl silicone polymer material, and 5 be cover plate, and 6 be miniature ultrasonic transducer units, and 7 be the higher-order of oscillation
Electric signal transmission cable, 8,15 respectively be positioned at different structure position two magnetic conductivity materials link, two magnetic conductivity
The link of material end-to-end relation each other in the structure shown here, 9,22 be two pole shoes positioned at different structure position respectively, 10,12,
14th, 17,19,21 be six pin joints in six diverse locations respectively, and 11,13,18,20 be to be in four different positions respectively
The link for the four non magnetic materials put, 16 be magnet exciting coil, and 23 be infusion tube, and 24 be Micropump;The chain ring type in legend
Magnetic holding device structure is only the legend structure of signal, and the actual chain ring type magnetic holding device structure is not limited to the legend chain ring type electromagnetism
Clamp structure;Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, its try
The flow direction of sample liquid stream.
Embodiment
In this case that Fig. 1 and Fig. 2 are shown embodiment, its main points of the example are, the structure of the device includes micro-fluidic
Chip, the structure of the micro-fluidic chip include being bonded to each other the substrate 4 and cover plate 5 of installing together, the substrate 4 and cover plate 5
It is plate object or tablet, that face towards the cover plate 5 of the substrate 4 is contained to be formed via mould pressing process or etching technics
Channel structure, be bonded to each other the substrate 4 that is installed together and be built into the miniflow containing pipeline configuration jointly with the cover plate 5
Chip is controlled, the locations of structures of the pipeline is located at the juncture area that the substrate 4 is bonded to each other with the cover plate 5, the both ends point of the pipeline
It is not connected with the sample introduction end 3 of the micro-fluidic chip and terminal 2, the sample introduction end 3 is the injection of the micro-fluidic chip sample solution
End, the terminal 2 are the terminals of sample solution flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, and the terminal 2 is with being somebody's turn to do
Sample introduction end 3 is located remotely from each other, and the distance between the terminal 2 and the sample introduction end 3 are between 3 centimetres and 10 centimetres, the terminal 2 and end
End liquid pool links together, and 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 for receiving
The sample solution of terminal 2 is flow to via the pipeline, in the pipeline on diverse location in order or backward be equiped with work electricity
Pole and to electrode and reference electrode, the order refers to its locations of structures of the reference electrode closer to the terminal 2
Position, the backward refer to the reference electrode locations of structures closer to the position of sample introduction end 3, and the working electrode is by leading
Conductive electrodes and the gold size sensitive membrane for having embedded tumor markers antibody being attached on the conductive electrode are formed, the pipeline
Construction parallel construction is presented, the pipeline in parallel construction is made up of seven lateral parallel connections, the presentation structure in parallel
The pipeline its appearance profile made is similar to the profile of parallel circuit, and the quantity of the working electrode is seven, seven works
The installation position for making electrode is located in seven laterals respectively, and, its top layer gold size of seven working electrodes is sensitive
Tumor markers antibody in membrane structure is that the seven kinds of tumor markerses that can be specifically bound to tumor markers antigen resist respectively
Body material, seven kinds of antibody materials are tumor markers antibody CA199, CA242, AFP, EB, CEA, TPSA and FPSA respectively,
The antigen is the antigen of broad sense, and the antibody is the antibody of broad sense, and its material of the working electrode is argent material, gold
Column, sheet or thread is presented in material, carbon material or thermal decomposition conducting polymer material, its pattern of the working electrode, should
Its material of substrate 4 is dimethyl silicone polymer material, and its surface of substrate 4 is the surface of primary form, the table of the primary form
Face its be intended to refer to the not no primary form of the material by any surface chemical modification or any surface chemical modification
Surface, the structure of the device also include chain ring type magnetic holding device 1, and six links are shared in its structure of the chain ring type magnetic holding device 1
8th, 11,13,15,18,20, the link 8,11,13,15,18,20 in strip, shaft-like or bar-shaped, mutually cut with scissors by each adjacent link
Connect to form chain link, the hexagonal cyclic structure of its appearance profile of the chain link, each drift angle 10 of the hexagonal annular structure, 12,
14th, 17,19,21 its locations of structures are articulated structure position, and two therein of the hexagonal annular structure is in opposite side position
Link 8,15 its material be magnetic conductivity material, its material of the remaining four processes 11,13,18,20 of the hexagonal annular structure
It is non-magnetic material, the non magnetic material refers to the material not responded strongly to externally-applied magnetic field, the magnetic conductivity material
Two links among a link 15 on be wound with magnet exciting coil 16, the link 15 for being wound with magnet exciting coil 16 is encouraged at it
The pole shoe of a magnetic conductivity material is respectively equiped with the both sides neighbor positions of magnetic coil 16, shares two pole shoes 9,22, should
Two pole shoes 9,22 are directed to the link 8 of another magnetic conductivity material, and the link 8 of another magnetic conductivity material is pasted on its surface
Attached fixation is equiped with miniature ultrasonic transducer units 6, relies on the chain ring type magnetic holding device 1 socket of electromagnetism adhesive strength to be positioned at this
The close position of its terminal 2 of micro-fluidic chip, and, higher-order of oscillation electric signal transmission cable 7, the higher-order of oscillation electric signal
One end of transmission cable 7 links together with the miniature ultrasonic transducer units 6;The chain ring type magnetic holding device 1 provides a side
Just the function that the device is disassembled;Its major function of the miniature ultrasonic transducer units 6 be in the actual sample introduction test of micro-fluidic chip,
The ultrasonic wave launched using it is opened to reduce the interface between sample solution and the inwall of its inner passage of micro-fluidic chip
Power, can be compatible, also, utilizes the sample introduction end 3 and the terminal 2 and the miniature ultrasonic transducer units 6 installing position
The distance between put the difference on difference and its ultrasonic intensity experienced, its interface of sample introduction end 3 described in induced synthesis
Difference between tension force and the terminal 2 its interfacial tension, the interfacial tension difference meeting between the micro-fluidic chip both ends 2,3
Pressure gap is formed between the both ends 2,3 of the micro-fluidic chip, the pressure gap can drive sample solution to the terminal 2
Flow in direction;The ultrasonic wave that its function of the miniature ultrasonic transducer units 6 also includes being launched with it is checked contained in sample
Its absorption on the micro-fluidic chip its inner passage inner surface of large biological molecule, and then check the dimethyl silicone polymer material
Swallow up effect of its body phase of the substrate 4 of matter to the large biological molecule;The dimethyl silicone polymer material that is soft and having elasticity
Its function of substrate 4 includes, with its property to the strong absorption of ultrasonic wave, absorbing ultrasonic wave strongly, and thereby in the miniflow
Control chip terminal 2 is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 3;And
Micropump 24, the Micropump 24 are connected with the sample introduction end 3;The function of the Micropump 24 is, the sample solution and the micro-fluidic chip its
Interfacial tension between the inwall of inner passage is reduced, under the increased precondition of alternate compatibility by the ul-trasonic irradiation,
Its institute of interfacial tension difference come with the mechanicalness pumping strength of the Micropump 24 between the both ends 2,3 of ultrasonic wave induction
The driving force brought is supported mutually, adjusts mutually, is mutually coupled, and one driving test liquid is pooled in a manner of Collaboration
Flow to the strength of the direction of terminal 2 flowing, be filled with some high hydroscopic resin particles in the terminal liquid pool, the terminal liquid pool its
Opening end is covered by breathable microporous film.
Arrow in legend indicate the micro-fluidic chip its in actual motion, by both ends 2,3 pressure differentials drive, its
The flow direction of sample liquid stream.
The associate members such as the higher-order of oscillation electric signal generator are depicted without in Fig. 1 and Fig. 2.
Involved magnetic conductive material and involved nonmagnetic substance market are on sale.
Involved miniature ultrasonic transducer units 6 are commercially available;It can also be customized to ultrasonic transducer producer.
The Micropump 24 can customize to specialized factory.
Involved higher-order of oscillation electric signal transmission cable 7 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 be customized to relevant manufacturers
Its inner passage of the micro-fluidic chip involved by this case is the pipeline of hydrophobic capillary form.
The word of Micropump one art-recognized meanings of itself are known for the professional in micro-fluidic chip field.
For example miniature piezoelectric pump of the Micropump, miniature peristaltic pump, miniature air driven pump, etc..
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.Micropump in legend is external
The Micropump of form;The Micropump can certainly do into or say sample introduction end or its neighbour knot inside the embedded microfluidic chip structure
The Micropump of the built in version of structure position, its basic structure key element are identical with 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. the classifiable tumor mark joint inspection chip apparatus suitable for male's physical examination examination, it is characterised in that the structure of the device
Including micro-fluidic chip, the structure of the micro-fluidic chip includes being bonded to each other the substrate and cover plate of installing together, the substrate
It is plate object or tablet with cover plate, that face towards the cover plate of the substrate is contained via mould pressing process or etching technics
The channel structure of formation, it is bonded to each other the substrate being installed together and has been built into jointly containing the micro- of pipeline configuration with the cover plate
Fluidic chip, 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 point of the pipeline
It is not connected with the sample introduction end of the micro-fluidic chip and terminal, the sample introduction end is the injection end of the micro-fluidic chip sample solution,
The terminal 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
It is located remotely from each other, between 3 centimetres and 10 centimetres, the terminal contacts with terminal liquid pool for the distance between the terminal and the sample introduction end
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 the pipeline
The sample solution of terminal is flow to, in the pipeline on diverse location in order or backward is 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, the backward
The reference electrode locations of structures is referred to closer to the sample introduction end position, the working electrode is by conductive electrode and patch
The gold size sensitive membrane for having embedded tumor markers antibody being attached on the conductive electrode is formed, and parallel connection is presented in the construction of the pipeline
Construction, the pipeline in parallel construction is made up of seven lateral parallel connections, the pipeline of the presentation parallel construction its
Appearance profile is similar to the profile of parallel circuit, and the quantity of the working electrode is seven, the installing position of seven working electrodes
Put respectively in seven laterals, and, the tumour in its top layer gold size sensitivity membrane structure of seven working electrodes
Mark antibody is the seven kinds of tumor markers antibody materials that can be specifically bound to tumor markers antigen respectively, and this seven kinds anti-
Body material is tumor markers antibody CA199, CA242, AFP, EB, CEA, TPSA and FPSA respectively, and the antigen is broad sense
Antigen, the antibody is the antibody of broad sense, and its material of the working electrode is argent material, gold material, carbon material
Or column, sheet or thread is presented in thermal decomposition conducting polymer material, its pattern of the working electrode, its material of the substrate is poly-
Dimethyl siloxane material, its surface of the substrate are the surfaces of primary form, the surface of the primary form its be intended to refer to not
There are the surface of the primary form by any surface chemical modification or the material of any surface chemical modification, the structure of the device
Also include chain ring type magnetic holding device, six links are shared in its structure of the chain ring type magnetic holding device, the link is in strip, bar
Shape is bar-shaped, and each adjacent link is hinged to form chain link, the hexagonal cyclic structure of its appearance profile of the chain link, the hexagon
Its locations of structures of each drift angle of cyclic structure is articulated structure position, two therein of the hexagonal annular structure in pair
Its material of the link of side position is magnetic conductivity material, and its material of the remaining four processes of the hexagonal annular structure is non magnetic
Material, the non magnetic material refer to the material not responded strongly to externally-applied magnetic field, two links of the magnetic conductivity material
Among a link on be wound with magnet exciting coil, this is wound with both sides neighbour position of the link in its magnet exciting coil of magnet exciting coil
The pole shoe for being respectively equiped with a magnetic conductivity material is put, shares two pole shoes, two pole shoes are directed to another magnetic conduction
Property material link, fixation is attached on its surface of the link of another magnetic conductivity material and is equiped with miniature ultrasonic transducer units,
The chain ring type magnetic holding device socket of electromagnetism adhesive strength is relied on to be positioned at the close position of its terminal of the micro-fluidic chip,
And higher-order of oscillation electric signal transmission cable, one end of the higher-order of oscillation electric signal transmission cable and the miniature ultrasonic transducing
Device links together;The chain ring type magnetic holding device provides a function of facilitating the device to disassemble;The miniature ultrasonic transducing
Its major function of device be in the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it reduce sample solution with
Interfacial tension between the inwall of its inner passage of micro-fluidic chip, can be compatible, also, using the sample introduction end with
And the distance between the terminal and the miniature ultrasonic transducer units installation position difference and its ultrasonic wave experienced it is strong
Difference between difference on degree, its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension, the miniflow
Interfacial tension difference between the control chip both ends can form pressure gap between the both ends of the micro-fluidic chip, the pressure
Difference can drive sample solution to the end flow;Its function of the miniature ultrasonic transducer units also includes surpassing with what it was launched
Sound wave checks in sample contained large biological molecule its absorption on the micro-fluidic chip its inner passage inner surface, and then
Check swallow up effect of its body phase of the substrate of the dimethyl silicone polymer material to the large biological molecule;Softness simultaneously has being somebody's turn to do for elasticity
Its function of the substrate of dimethyl silicone polymer material is included with its property to the strong absorption of ultrasonic wave, ultrasonic wave is carried out strong
Absorb, and thereby realize ultrasonic intensity within micro-fluidic chip terminal to the limited short distance between the sample introduction end
Rapid decrement;And Micropump, the Micropump are connected with the sample introduction end;The function of the Micropump is, in the sample solution and the miniflow
Interfacial tension between the inwall of its inner passage of control chip is reduced, the increased premise of alternate compatibility by the ul-trasonic irradiation
Under the conditions of, the interfacial tension difference come between the both ends of ultrasonic wave induction with the mechanicalness of Micropump pumping strength its
Caused driving force is supported mutually, adjusts mutually, is mutually coupled, and one driving sample is pooled in a manner of Collaboration
The strength that liquid stream flows to the terminal direction, the terminal liquid pool is interior to be filled with some high hydroscopic resin particles, the terminal liquid pool
Its opening end is covered by breathable microporous film.
2. the classifiable tumor mark joint inspection chip apparatus according to claim 1 suitable for male's physical examination examination, it is special
Sign is that it is capillary channel that the pipeline, which includes the lateral,.
3. the classifiable tumor mark joint inspection chip apparatus according to claim 1 suitable for male's physical examination examination, it is special
Sign is that the thermal decomposition conducting polymer is the electric conductivity material formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated
Material.
4. the classifiable tumor mark joint inspection chip apparatus according to claim 1 suitable for male's physical examination examination, it is special
Sign is, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the working electrode
Length is between 1 micron to 15000 microns.
5. the classifiable tumor mark joint inspection chip apparatus according to claim 1 suitable for male's physical examination examination, it is special
Sign is that the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. the classifiable tumor mark joint inspection chip apparatus according to claim 1 suitable for male's physical examination examination, it is special
Sign is, the cover plate its material in structure is dimethyl silicone polymer material.
7. the classifiable tumor mark joint inspection chip apparatus according to claim 1 suitable for male's physical examination examination, it is special
Sign is that the Micropump is miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.
8. the classifiable tumor mark joint inspection chip apparatus according to claim 1 suitable for male's physical examination examination, it is special
Sign is that described its thickness of cover plate and substrate in structure is between 1.0 millimeters and 5.0 millimeters.
9. the classifiable tumor mark joint inspection chip apparatus according to claim 1 suitable for male's physical examination examination, it is special
Sign is that the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission electricity
Its other end of cable is connected with the higher-order of oscillation electric signal generator.
10. the classifiable tumor mark joint inspection chip apparatus according to claim 1 suitable for male's physical examination examination, it is special
Sign is that for its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units between 5 milliwatts and 5000 milliwatts, this is miniature super
The frequency of its ultrasonic wave operationally launched of acoustic wave transducer is between 100KHz and 12MHz.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610703590.3A CN107694642A (en) | 2016-08-09 | 2016-08-09 | Classifiable tumor mark joint inspection chip apparatus suitable for male's physical examination examination |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610703590.3A CN107694642A (en) | 2016-08-09 | 2016-08-09 | Classifiable tumor mark joint inspection chip apparatus suitable for male's physical examination examination |
Publications (1)
Publication Number | Publication Date |
---|---|
CN107694642A true CN107694642A (en) | 2018-02-16 |
Family
ID=61168931
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610703590.3A Pending CN107694642A (en) | 2016-08-09 | 2016-08-09 | Classifiable tumor mark joint inspection chip apparatus suitable for male's physical examination examination |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN107694642A (en) |
-
2016
- 2016-08-09 CN CN201610703590.3A patent/CN107694642A/en active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107694619A (en) | Ten Five-channel micro flow control chip devices of common tumor markers examination | |
CN107126985A (en) | Six passage co-detections of tumor markers in benign micro flow control chip devices of compact in architecture | |
CN107126983A (en) | A kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes | |
CN107126984A (en) | Co-detections of tumor markers in benign couples the micro flow control chip device of running with dual drive | |
CN107694637A (en) | A variety of everywoman's co-detections of tumor markers in benign micro flow control chip devices | |
CN107694635A (en) | Six kinds of classifiable tumor mark multichannels while detection micro flow control chip device | |
CN107694642A (en) | Classifiable tumor mark joint inspection chip apparatus suitable for male's physical examination examination | |
CN106814184A (en) | The tumor markers joint-detection six-channel microfluidic chip device simplified | |
CN107694643A (en) | Six passage co-detections of tumor markers in benign micro flow control chip devices of compact in architecture | |
CN106807457A (en) | Various everywoman's co-detections of tumor markers in benign micro flow control chip devices | |
CN107703301A (en) | A kind of co-detections of tumor markers in benign chip apparatus suitable for women physical examination examination purposes | |
CN107694625A (en) | Co-detections of tumor markers in benign couples the micro flow control chip device of running with dual drive | |
CN106568952A (en) | Micro-fluidic chip device for simultaneously detecting women's various typical tumor markers | |
CN107694628A (en) | Couple dual drive male's classifiable tumor mark joint inspection chip apparatus | |
CN107694621A (en) | The male tumor mark joint inspection chip apparatus of two kinds of type of drive coupling runnings | |
CN107694627A (en) | The special main six kinds of co-detections of tumor markers in benign chip apparatus of type of drive | |
CN107694624A (en) | Six kinds of classifiable tumor mark joint inspection chip apparatus of dual drive coupling running | |
CN107694620A (en) | Integrated women classifiable tumor mark joint inspection chip apparatus | |
CN107694641A (en) | With reference to male's classifiable tumor mark joint inspection chip apparatus of hydrophobic cheap substrate | |
CN107694629A (en) | The female tumor mark joint inspection chip apparatus of more type of drive coupling runnings | |
CN107694630A (en) | Using the chip apparatus for joint inspection Diagnostic Value of Several Serum Tumor Markers of hydrophobic substrate | |
CN107132355A (en) | Classifiable tumor mark joint inspection chip apparatus suitable for male's physical examination examination | |
CN107694623A (en) | Co-detections of tumor markers in benign chip apparatus using PDMS as the dual drive of substrate | |
CN107694645A (en) | Generally investigate ten Five-channel micro flow control chip devices of tumor markers | |
CN107694626A (en) | The co-detections of tumor markers in benign chip apparatus for taking the dual drive of integrated architecture to couple |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180216 |
|
WD01 | Invention patent application deemed withdrawn after publication |