CN106694063A - Micro-fluidic chip device used for typical tumor marker joint detection and suitable for males - Google Patents
Micro-fluidic chip device used for typical tumor marker joint detection and suitable for males Download PDFInfo
- Publication number
- CN106694063A CN106694063A CN201510827335.5A CN201510827335A CN106694063A CN 106694063 A CN106694063 A CN 106694063A CN 201510827335 A CN201510827335 A CN 201510827335A CN 106694063 A CN106694063 A CN 106694063A
- Authority
- CN
- China
- Prior art keywords
- micro
- substrate
- fluidic chip
- tumor markers
- terminal
- 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
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Cell Biology (AREA)
- Biomedical Technology (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Hospice & Palliative Care (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Clinical Laboratory Science (AREA)
- Dispersion Chemistry (AREA)
- Oncology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
Abstract
The invention relates to a micro-fluidic chip device used for typical tumor marker joint detection and suitable for males and belongs to the field of analytical test. Polydimethylsiloxane, namely PDMS is used for manufacturing a substrate of a micro-fluidic chip for male typical tumor marker joint detection, many advantages are generated, but a series of problems exist. The scheme aims at the problems. According to the scheme, the substrate is selected from PDMS with the original ecology surface, a minitype ultrasonic transducer is attached to a position adjacent to a sample liquid flow terminal of the micro-fluidic chip, interfacial tension is ultrasonically reduced, and the compatibility between relevant phases is greatly improved; through the high absorption capacity of PDMS to ultrasonic waves, the ultrasonic intensity is rapidly and gradually reduced within a short distance, the interfacial tension difference is formed between the two ends of the chip, the pressure difference is formed between the two ends through the interfacial tension difference, and the pressure difference drives sample liquid flow to flow to the terminal along an original hydrophobic pipeline. No micro-pump needs to be used for the device.
Description
Technical field
The present invention relates to the classifiable tumor markers in detecting micro flow control chip device that a kind of male is applicable, belong to analysis test
Field.
Background technology
Tumor markers (tumor marker, TM) refers in the generation and breeding of tumour, to be produced in itself by tumour cell
It is raw or by body to tumour cell react and produce, reflection tumour exist and growth a class material, including protein,
Hormone, enzyme (isodynamic enzyme) and oncoprotein etc..Tumor markers in chemical examination blood samples of patients or body fluid, can be in cancer screening
Early detection tumour, and observe the curative effect of oncotherapy and judge patient's prognosis.Clinically conventional tumor markers has at present：
(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)
It is 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)
It is 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 swollen ECC, trophoblastic tumor (suede cancer, vesicular mole) etc.
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 for clinically detecting 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 tumor markers exceptions；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 is may refer to soon
Before the monograph " diagram Microfluid based Lab on a chip " that goes out, the monograph publishes via Science Press, and the monograph is for micro-fluidic
Past of technology, now, and, vision of the future etc. aspect, suffer from detail, be deep into long discussion of detail.
So, the focal issue that this case that to have a talk below pays special attention to.
The basic framework of micro-fluidic chip, including the substrate and the cover plate that fits together therewith of small fluid course are etched with,
Small fluid course on the substrate, before upper cover plate is assembled, it is apparent on see to be exactly some micro-channels, be when 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 the 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 can be with identical, it is also possible to differ；From material consumption, manufacture difficulty and
Application popularization prospect etc. aspect from the point of view of, 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 suppressed or etched thereon, and the cover plate made with glass or the cheap material such as polypropylene or other plastic sheets is engaged,
It is seemingly a kind of more satisfactory selection；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 not carrying out the modified operation for the micro-channel surface, then,
After overall assembling is completed, that is, after covering cover plate, because of structure in the micro-channel its inner surface occupy most liquid circulation
The inner surface in road, then, the PDMS micro-channels inner surface its strong hydrophobic property is deciding factor, and 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
It is another problem into serious technical puzzlement：PDMS polymer molecules tool inside this PDMS material substrate its body phase
There is the characteristic for diffusing to the surface automatically, migrating, this substrate body phase inside PDMS polymer molecules are diffused to the surface, moved automatically
The characteristic of shifting, by cause by that micro-channel of surface modifying and decorating its inner surface it is modified after state can not maintain foot
Enough long time, being held time for micro-channel its inner surface state after that is surface-modified be substantially only sufficient in completion laboratory
The time of portion's test experiments needs；In other words, PDMS micro-channel inner surfaces of or surface modification modified by surface, its
After modified or say the surface state formed after modification can not be lasting, but soon automatically tend to or say 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, does not do if surface modification, and the fine liquid stream of polar solvent similar to the aqueous solution cannot pump
Send and pass through, chip also cannot just be used；And if having done surface modification, its state after modifying cannot be persistently kept again, also
Being equally cannot 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 cannot persistently, chip cannot 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, the depression that these adsorbed large biological molecules can also be further further on PDMS surfaces gradually falls into gradually deep, directly
It is trapped within the body phase of PDMS substrates to heavy, in fact, this process is partly also due to inside PDMS material body phase
Polymer molecule have diffuse to the surface, caused by travel motion；Such case, it is also possible to explained from another angle, i.e.
Continuously from inside PDMS body phases to its diffusion into the surface, those polymer molecules of migration, the result of its motion, 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 to be related to the severe deviations of all kinds of test data of experiment of large biological molecule.
As described above, the problem of PDMS substrates is, 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 surface saturation is adsorbed, 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 is explained, there are substantial amounts of Minute pores in PDMS body phases, associated biomolecule macromolecular 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 clamp-ons 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.
In order to prevent this PDMS substrate bodies relative to the effect of swallowing up of large biological molecule, can be from containment PDMS surfaces opposite
The absorption of thing macromolecular is addressed, method be chemically modified aiming at the PDMS material surface it is modified, for
For PDMS is for the situation of substrate material, exactly the surface of described micro-channel part is chemically modified it is modified, 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 cannot persistently keep, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface automatically,
The process of migration, soon can become that again script strong and dredge by the micro-channel inner surface state that surface chemical modification is modified
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
Substrate its micro-channel inner surface is always rapidly to strong hydrophobic surface state evolution.
So, how can either obtain that PDMS material price is extremely cheap, substrate makes extremely easy benefit, 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 thorny problem.The problem makes the numerous specialties in this area as another problem addressed above, equally
Personnel are entangled with, perplex 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.
The content of the invention
The technical problems to be solved by the invention are to provide a package solution, solve what is addressed above totally
Two problems, also, the solution is applied to build a kind of new can especially need concern for male's physical examination is belonged to
Seven kinds than more typical primary tumor mark carry out simultaneously examination, while detection micro flow control chip device.
The present invention solves the technical problem by following scheme, and the device that the program is provided is that the typical case that a kind of male is applicable swells
Tumor markers joint-detection micro flow control chip device, program feature is that the structure of the device includes multichannel micro-fluidic chip,
The structure of the micro-fluidic chip includes installing substrate and cover plate together bonded to each other, the substrate and cover plate be plate object or
Contain the channel structure formed via mould pressing process or etching technics, the base in tablet, that face towards the cover plate of the substrate
Piece also contains and be connected with the channel structure and pierce being formed via mould pressing process, etching technics or simple drilling technology for the substrate
Window structure, substrate being installed together bonded to each other and the cover plate have been built into containing pipeline configuration and phase therewith jointly
The micro-fluidic chip of liquid pool structure even, the locations of structures of the pipeline is located at the substrate and cover plate interface zone bonded to each other,
Its side of the window is blocked by the cover plate and opposite side is opened, and the locations of structures of the window is exactly the locations of structures of the liquid pool, institute
Stating liquid pool has two kinds, and two kinds of liquid pools are respectively the sample introduction end liquid pool and terminal liquid pool for being located at different structure position, and this is micro-fluidic
The sample introduction end position of chip has one or more sample introduction end liquid pool, and the sample introduction end refers to the micro-fluidic chip reality
The injection end position of detected solution during the sample introduction of border, then has a terminal liquid pool in the terminal location of the micro-fluidic chip, described
Terminal refers to the terminal location of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, the terminal and the sample introduction end
Be located remotely from each other, one end of the pipeline and the sample introduction end liquid pool UNICOM for being located at sample introduction end, the other end of the pipeline be located at that this is micro-
The terminal liquid pool UNICOM of the terminal of fluidic chip, and, sequentially or backward be respectively installed in the pipeline it is different
Working electrode on position and to electrode and reference electrode, the order refers to the reference electrode its locations of structures and more leans 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,
The construction of the pipeline is presented parallel construction, and the pipeline in parallel construction is made up of seven lateral parallel connections, and the presentation is simultaneously
The pipeline its appearance profile for joining construction is similar to the profile of parallel circuit, and the quantity of the working electrode is seven, this seven
The installation position of working 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 respectively the seven kinds of tumor markers antibody that can be specifically bound to tumor markers antigen
Material, seven kinds of antibody materials are respectively tumor markers antibody CA199, CA242, AFP, EB, CEA, TPSA and FPSA,
The antigen is the antigen of broad sense, and the antibody is the antibody of broad sense, and the working electrode its material is argent material, gold
Material, carbon material or thermal decomposition conducting polymer material, the working electrode its pattern presentation column, sheet or thread, should
Substrate its material is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, the surface of the primary form its
It is 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, should
The structure of device also includes miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, the higher-order of oscillation electric signal
One end of transmission cable links together with the miniature ultrasonic transducer units, and it is micro- that the miniature ultrasonic transducer units are installed in this with attaching
The position of the cover plate of fluidic chip or the neighbouring described terminal of substrate；The miniature ultrasonic transducer units its major functions is micro-fluidic
When the actual sample introduction of chip is tested, the ultrasonic wave launched using it reduces the interface between sample solution and the inwall of the pipeline
Tension force, can be compatible, also, using the sample introduction end and the terminal and the miniature ultrasonic transducer units installation position
The distance between difference on difference and its ultrasonic intensity experienced, its interfacial tension of sample introduction end described in induced synthesis with
Difference between the terminal its interfacial tension, the interfacial tension difference between the micro-fluidic chip two ends can be in the micro-fluidic core
Pressure gap is formed between the two ends of piece, the pressure gap can drive sample solution to the end flow；The miniature ultrasonic
Transducer its function also include the ultrasonic wave launched with it check contained large biological molecule in sample its in the pipeline
Absorption on 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；
Its function of the substrate of the dimethyl silicone polymer material is including with cover plate and working electrode and to electrode and the isomorphism of reference electrode one
Build the micro-fluidic chip, it is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and also include with it to ultrasonic wave
The strong property for absorbing, 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.
The tumor markers antibody is the antibody of broad sense, and the antibody of the broad sense is referred to possessing antibody function or is functionally similar to
Can be combined with the various involved tumor markerses of corresponding clinic and forming immune complex or immune compound 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 corresponding
Antibody or be functionally similar to antibody material carry out enzyme mark detection it is various clinical involved the need for differentiate, the tumor-marker of detection
Thing.
The gold size sensitive membrane is to be sufficiently mixed uniformly shitosan gold size solution and tumor markers antibody-solutions, uses point sample instrument
Point sample coats specified structure position, and forms its drying and forming-film.Tumor markers antibody in the gold size sensitive membrane is equal
It is the tumor markers antibody that horseradish peroxidase or glucose oxidase are marked, 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 shitosan, 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, but, for prepare liquid sample and the consideration of the aspect such as reagent loss is reduced less as far as possible, described in the pipeline includes
The passage of the preferred capillary level of lateral, the passage of the capillary level implies that the interior of the capillary on its internal diameter and 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
With the extension of pipeline, the shape of cross section of different parts can also allow to be different shapes the interior shape of tubule.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 related to several liquid pools in this case microfluidic chip structure, the liquid pool is the pond shape or scrotiform structure for transitional liquid storage
Make, its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, the cavity shape such as cylindrical empty
Cavity-like, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..
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 only with millimeter calculate magnitude.
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；Together
Sample ground, the technology of hole-opening is even more known simple technique on naked PDMS substrates.This case is not also to this expansion superfluous words.
The industrial products market of involved its all size of higher-order of oscillation electric signal transmission cable is on sale.
The structure of the micro fluidic device can also include higher-order of oscillation electric signal generator；The higher-order of oscillation electric signal transmission electricity
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, 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 the miniature ultrasonic transducer units its specified ultrasonic wave transmission powers be between 2 milliwatts and 2000 milliwatts it
Between；The preferred scope of the frequency of the miniature ultrasonic transducer units its ultrasonic waves operationally launched 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
To electrode and reference electrode etc., can respectively via corresponding special the corresponding interface got lines crossed with the multiple tracks electrochemical workstation
Coupled.It is described that special to get lines crossed be for each electrode is carried out into phase with each the corresponding interface of the multiple tracks electrochemical workstation
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, and according to actual needs, the micro-valve can be installed in any required position installed in the microfluidic chip structure；
For the professional of micro fluidic chip technical field, the art-recognized meanings of itself are known to the word of micro-valve one；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 for using, 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 for using, it is however recommended to or to say the preferred length its scope 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
Sense film, its thicknesses of layers can allow be any setting the sample measuring liquid treated occur electrical signals response thickness, but, push away
Preferred thickness is between 10 nanometers and 200 nanometers to the thickness recommended in other words conj.or perhaps.
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
Into the micro-fluidic chip of only 2.0 centimetres to 3.0 centimetres of super-small of length, and realized to ultrasonic wave in the extremely short distance
Extremely fast decay, it may be preferred to dimethyl silicone polymer is 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 distance between the terminal and described sample introduction end do not limit；But, the terminal and the distance between the sample introduction end
Preferred scope is between 3 centimetres and 10 centimetres.
The cover plate and substrate its thickness can allow be any setting the thickness for being easy to assembling, the thickness of recommendation or say preferably
Thickness be between 1.0 millimeters and 5.0 millimeters.Less thickness is conducive to material-saving.
The application method of this case micro-fluidic chip：
Proposed first based on this case and the first public New stream driving principle, this case micro-fluidic chip its application running
In, the New stream driving method is determined completely without involving any additional Micropump.
The interfacial tension difference of this case to be formed between the micro-fluidic chip two ends caused by the ultrasonic wave, drives liquid
Stream flows in the hydrophobic capillary channel of seven channel microfluidic chip, using multi-channel electrochemical analyzer device respectively to seven kinds
Tumor markers antigen carries out joint-detection.
The specific detection of this case micro-fluidic chip is as follows using step：
1st, blood serum sample liquid is added in micro-pipe road, under ultrasonic wave driving, various tumor markers antigen molecules are each
In passage on electrode surface gold size sensitive membrane embedding corresponding horseradish peroxidase-labeled tumor markers 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
The curent change for causing, is derived from the species and content of various analytes.
4th, result is carried out into comprehensive analysis, comprehensive diagnos is carried out to tumor markers antigen.
It is an advantage of the invention that install miniature ultrasonic in its close position attaching of the terminal of the micro-fluidic chip changing
Can device, low-power, the ultrasonic wave of high-frequency band that using the miniature ultrasonic transducer units, it is launched so that without coming to the surface
The compatibility learned between modified strong hydrophobic its tube wall of micro-fluidic chip internal pipeline and the test object aqueous solution 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 the only several centimeters the sample introduction end
In the very short distance of yardstick, the rapid decrement of ultrasonic intensity is reached, thereby cause institute at the two ends of the micro-fluidic chip
The difference of interfacial tension is stated, and then, using the pressure between its two ends for being formed of the difference of the interfacial tension between the two ends
Difference, drives test liquid stream to be flowed to the terminal direction in such a originally strong hydrophobic capillary channel.By this
Case liquid stream drive scheme, entirely without any coming to the surface must be carried out to the substrate of the dimethyl silicone polymer material and its internal pipeline
Modification or chemical modification are learned, the laborious procedures of the surface chemical modification or chemical modification have been altogether dispensed with；And altogether dispense with biography
The equipment of the Micropump in system meaning etc；On the other hand, the ultrasonic wave of the low-power, high-frequency band, additionally it is possible in containing sample
Absorption of the large biological molecule on literalness naked its inner surface of pipeline of dimethyl silicone polymer substrate, and then contain that this gathers
Swallow up effect of its body phase of dimethyl siloxane piece to the large biological molecule；The antigen, antibody and antigen and antibody
Reversible binding thing is all belonging to the type of described large biological molecule certainly；Due to described suction-operated and the described work that swallows up
With effectively being contained, therefore, dependence test result will be better able to objectively reflect actual conditions；The low-power, height are again and again
The effect of section ultrasonic wave, also includes that facilitates the Reversible binding between antigen, antibody to react quickly reaches certainly, and this causes correlation
Test operation can be completed with than speed faster.
Due to the surface chemical modification for the dimethyl silicone polymer substrate its relevant surfaces or chemical modification behaviour need not be carried out
Make, therefore, this surface chemical modification layer or chemically modified layer not need presence, then, the dimethyl silicone polymer
Substrate its body phase interior polymer molecule constantly diffuses to the surface automatically, migrate caused by it to surface chemical modification layer or
The damaging influence of chemically modified layer does not just exist yet.
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 very cheap polydimethyl siloxane material of this kind is just possible in micro-fluidic chip system
Standby, production, using etc. field play bigger effect.
This case micro-fluidic chip its highly integrated structure, measures the need for determining it among practical application to test serum
Smaller, this contributes to the body and mind for reducing related subject to damage.
Brief description of the drawings
Fig. 1 is its rough outside side view of this case micro flow control chip device.
In figure, 1 is the substrate of dimethyl silicone polymer material, and 2 is cover plate, and 3 is higher-order of oscillation electric signal transmission cable, 4
It is miniature ultrasonic transducer units, 5 is the sample introduction end of the micro-fluidic chip, and 6 is the terminal of the micro-fluidic chip；Figure
Example in arrow indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, the flowing of its test liquid stream
Direction.
Specific embodiment
In this case that Fig. 1 is shown embodiment, the example is characterized in, the structure of the device includes multichannel micro-fluidic core
Piece, the structure of the micro-fluidic chip includes installing bonded to each other substrate 1 and cover plate 2 together, the substrate 1 and cover plate 2
Plate object or tablet are, that face towards the cover plate 2 of the substrate 1 is contained and formed via mould pressing process or etching technics
Channel structure, the substrate 1 also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics
Or the window structure that simple drilling technology is formed, substrate 1 being installed together bonded to each other and the cover plate 2 are built into jointly
Micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the locations of structures of the pipeline is located at the substrate 1 and is somebody's turn to do
The interface zone bonded to each other of cover plate 2, its side of the window is blocked by the cover plate 2 and opposite side is opened, the structure position of the window
Put be exactly the liquid pool locations of structures, the liquid pool has two kinds, and two kinds of liquid pools are respectively the sample introductions for being located at different structure position
There is the one or more sample introduction end liquid pool end liquid pool and terminal liquid pool, the position of sample introduction end 5 of the micro-fluidic chip,
The sample introduction end 5 refers to the injection end position of detected solution during the micro-fluidic chip actual sample introduction, at the end of the micro-fluidic chip
Holding 6 positions then has a terminal liquid pool, and the terminal 6 is referred to when the actual sample introduction of the micro-fluidic chip is tested in its chip
The terminal location of liquid flowing, the terminal 6 is located remotely from each other with the sample introduction end 5, one end of the pipeline and the institute positioned at sample introduction end 5
Sample introduction end liquid pool UNICOM is stated, the other end of the pipeline joins with the terminal liquid pool of the terminal 6 for being located at the micro-fluidic chip
It is logical, and, sequentially or backward be respectively installed in working electrode in the pipeline on diverse location and to electrode and reference
Electrode, the order refers to its locations of structures of the reference electrode closer to the position of the terminal 6, and the backward refers to institute
State reference electrode locations of structures closer to the position of sample introduction end 5, the working electrode is by conductive electrode and is attached to this and leads
The gold size sensitive membrane for having embedded tumor markers antibody on conductive electrodes is constituted, and the construction of the pipeline is presented parallel construction, described
It is made up of seven lateral parallel connections in the pipeline of parallel construction, its appearance profile of the pipeline of the presentation parallel construction is approximate
In the profile of parallel circuit, the quantity of the working electrode is seven, and seven installation positions of working electrode are located at described respectively
In seven laterals, and, the tumor markers antibody in the sensitive membrane structure of its top layer gold size 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 respectively tumour marks
Will thing antibody CA199, CA242, AFP, EB, CEA, TPSA and FPSA, the antigen is the antigen of broad sense, described anti-
Body is the antibody of broad sense, and the working electrode its material is that argent material, gold material, carbon material or thermal decomposition are conductive high
Molecule material, the working electrode its pattern is presented column, sheet or thread, and the substrate 1 its material is dimethyl silicone polymer
Material, its surface of substrate 1 is the surface of primary form, the surface of the primary form its be intended to refer to not by any table
The surface of the primary form of the material of face chemical modification or any surface chemical modification, the structure of the device also includes miniature ultrasonic
Wave transducer 4, and, higher-order of oscillation electric signal transmission cable 3, one end of the higher-order of oscillation electric signal transmission cable 3 with should
Miniature ultrasonic transducer units 4 link together, and the miniature ultrasonic transducer units 4 are installed in the cover plate of the micro-fluidic chip with attaching
2 or substrate 1 neighbouring described terminal 6 position；The miniature ultrasonic transducer units 4 its major functions is in micro-fluidic chip reality
When border sample introduction is tested, the ultrasonic wave launched using it reduces the interfacial tension between sample solution and the inwall of the pipeline,
Can be compatible, also, using the sample introduction end 5 and the terminal 6 and the installation position of miniature ultrasonic transducer units 4
The distance between difference on difference and its ultrasonic intensity experienced, its interfacial tension of sample introduction end 5 described in induced synthesis
With the difference between the terminal 6 its interfacial tension, interfacial tension difference between the micro-fluidic chip two ends 5,6 can be
Pressure gap is formed between the two ends 5,6 of the micro-fluidic chip, the pressure gap can drive sample solution to the terminal 6
Flowing；It is big that the miniature ultrasonic transducer units 4 its functions also includes that the ultrasonic wave launched with it checks contained biology in sample
Molecule its absorption on the inner surface of pipeline, and then check the substrate 1 of the dimethyl silicone polymer material its body phase to the life
The effect of swallowing up of thing macromolecular；The substrate 1 of the dimethyl silicone polymer material its function include with cover plate 2 and working electrode and
The micro-fluidic chip, the substrate 1 of the dimethyl silicone polymer material that is soft and having elasticity are together built to electrode and reference electrode
Its function also includes with its property to the strong absorption of ultrasonic wave, ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic core
The piece terminal 6 is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 5.
Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, its test liquid
The flow direction of stream.
Fig. 1 is depicted without the associate members such as the higher-order of oscillation electric signal generator and multiple tracks electrochemical workstation.
Involved miniature ultrasonic transducer units 4 are commercially available；Can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal transmission cable 3 is commercially available；Can also be customized to ultrasonic transducer producer or to cable
Specialized factory customizes.
Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；Can also be customized to relevant speciality producer.
The multi-channel electrochemical work station can be with commercially available；The multi-channel electrochemical work station can also be according to specific
Whereabouts specialised manufacturers are needed to customize.
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 say interface of getting lines crossed and couple.
Capillary on usual expression and significance refers to hydrophilic capillary glass tube；Capillary channel involved by this case is but hydrophobic
Capillary form pipeline.
In view of its form of this case related text expresses that it is described above pipeline of the presentation parallel construction 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. the classifiable tumor markers in detecting micro flow control chip device that male is applicable, it is characterised in that the structure of the device
Including multichannel micro-fluidic chip, the structure of the micro-fluidic chip includes installing bonded to each other substrate and cover plate together, described
Substrate and cover plate are plate object or tablet, and that face towards the cover plate of the substrate is contained via mould pressing process or etching work
The channel structure that skill is formed, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etch
The window structure that technique or simple drilling technology are formed, substrate being installed together bonded to each other is built into jointly with the cover plate
Micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the locations of structures of the pipeline is located at the substrate and the lid
Piece interface zone bonded to each other, its side of the window is blocked by the cover plate and opposite side is opened, and the locations of structures of the window is exactly
The locations of structures of the liquid pool, the liquid pool has two kinds, and two kinds of liquid pools are respectively the sample introduction end liquid pools for being located at different structure position
And terminal liquid pool, the sample introduction end position of the micro-fluidic chip has one or more sample introduction end liquid pool, the sample introduction
End refers to the injection end position of detected solution during the micro-fluidic chip actual sample introduction, then has in the terminal location of the micro-fluidic chip
One terminal liquid pool, the terminal refers to the terminal of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested
Position, the terminal is located remotely from each other with the sample introduction end, one end of the pipeline be located at sample introduction end the sample introduction end liquid pool UNICOM, should
The other end of pipeline be located at the micro-fluidic chip the terminal the terminal liquid pool UNICOM, and, sequentially or backward ground
The working electrode that is respectively installed in the pipeline on diverse location and to electrode and reference electrode, the order refers to described
Closer to the terminal location, the backward refers to the reference electrode locations of structures closer to institute to its locations of structures of reference electrode
State sample introduction end position, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded tumor markers
The gold size sensitive membrane of antibody is constituted, and the construction of the pipeline is presented parallel construction, and the pipeline in parallel construction is by seven branched pipes
Road is in parallel to be constituted, described that the profile that the pipeline of parallel construction its appearance profile is similar to parallel circuit, the work electricity is presented
The quantity of pole is seven, and seven installation positions of working electrode are located in seven laterals respectively, and, this seven
Tumor markers antibody in the sensitive membrane structure of its top layer gold size of working electrode is respectively can specificity knot to tumor markers antigen
Close seven kinds of tumor markers antibody materials, seven kinds of antibody materials be respectively tumor markers 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, the working electrode
Its material is argent material, gold material, carbon material or thermal decomposition conducting polymer material, the working electrode its pattern
Column, sheet or thread is presented, the substrate its material is dimethyl silicone polymer material, and its surface of the substrate is primary form
Surface, the surface of the primary form its be intended to refer to not by any surface chemical modification or any surface chemical modification should
The surface of the primary form of material, the structure of the device also includes miniature ultrasonic transducer units, and, higher-order of oscillation electric signal is passed
Transmission cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable link together, the miniature ultrasonic
Wave transducer is installed in the position of the neighbouring described terminal of the cover plate or substrate of the micro-fluidic chip with attaching；The miniature ultrasonic is changed
Can device its major function be when the actual sample introduction of micro-fluidic chip is tested, the ultrasonic wave launched using it reduce sample solution and
Interfacial tension between the inwall of the pipeline, can be compatible, also, using the sample introduction end and the terminal and is somebody's turn to do
Difference in the distance between miniature ultrasonic transducer units installation position difference and its ultrasonic intensity experienced, induces shape
Difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension, the boundary between the micro-fluidic chip two ends
Face tension difference can form pressure gap between the two ends of the micro-fluidic chip, and the pressure gap can drive sample solution to institute
State end flow；The miniature ultrasonic transducer units its functions also includes that the ultrasonic wave launched with it checks contained life in sample
Thing macromolecular its absorption on the inner surface of pipeline, and then check the substrate of the dimethyl silicone polymer material its body phase to this
The effect of swallowing up of large biological molecule；The substrate of the dimethyl silicone polymer material its function includes and cover plate and working electrode and right
Electrode and reference electrode together build the micro-fluidic chip, soft and have the substrate of the dimethyl silicone polymer material of elasticity its work(
Can also include with its property to the strong absorption of ultrasonic wave, ultrasonic wave is absorbed strongly, and thereby should in the micro-fluidic chip
Terminal is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end.
2. the classifiable tumor markers in detecting micro flow control chip device that male according to claim 1 is applicable, it is special
Levy and be, the pipeline is capillary channel including the lateral.
3. the classifiable tumor markers in detecting micro flow control chip device that male according to claim 1 is applicable, it is special
Levy and be, the thermal decomposition conducting polymer is the electric conductivity material formed after being heat-treated through anoxybiotic by polyimides or polyacrylonitrile
Material.
4. the classifiable tumor markers in detecting micro flow control chip device that male according to claim 1 is applicable, 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 classifiable tumor markers in detecting micro flow control chip device that male according to claim 1 is applicable, it is special
Levy and be, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. the classifiable tumor markers in detecting micro flow control chip device that male according to claim 1 is applicable, it is special
Levy and be, its material of the cover plate in structure is dimethyl silicone polymer material.
7. the classifiable tumor markers in detecting micro flow control chip device that male according to claim 1 is applicable, it is special
Levy and be, the distance between the terminal and the sample introduction end are between 3 centimetres and 10 centimetres.
8. the classifiable tumor markers in detecting micro flow control chip device that male according to claim 1 is applicable, it is special
Levy and be, the cover plate in structure and substrate its thickness are between 1.0 millimeters and 5.0 millimeters.
9. the classifiable tumor markers in detecting micro flow control chip device that male according to claim 1 is applicable, 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 classifiable tumor markers in detecting micro flow control chip device that male according to claim 1 is applicable, it is special
Levy and be, the miniature ultrasonic transducer units its specified ultrasonic wave transmission powers is between 2 milliwatts and 2000 milliwatts, and this is miniature
The frequency of ultrasonic transducer its ultrasonic wave operationally launched is between 100KHz and 12MHz.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510827335.5A CN106694063A (en) | 2015-11-17 | 2015-11-17 | Micro-fluidic chip device used for typical tumor marker joint detection and suitable for males |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510827335.5A CN106694063A (en) | 2015-11-17 | 2015-11-17 | Micro-fluidic chip device used for typical tumor marker joint detection and suitable for males |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106694063A true CN106694063A (en) | 2017-05-24 |
Family
ID=58933191
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510827335.5A Pending CN106694063A (en) | 2015-11-17 | 2015-11-17 | Micro-fluidic chip device used for typical tumor marker joint detection and suitable for males |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106694063A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101587124A (en) * | 2009-07-12 | 2009-11-25 | 宁波大学 | Micro-fluidic chip special for diagnosing syphilis by aid of organic conductor material technology |
| CN102608184A (en) * | 2012-03-08 | 2012-07-25 | 宁波大学 | Sleeved combination type glassy carbon electrode assembly with electric and acoustic dual-excitation function |
| WO2015107014A1 (en) * | 2014-01-15 | 2015-07-23 | Eth Zurich | Acoustophoretic droplet handling in bulk acoustic wave devices |
-
2015
- 2015-11-17 CN CN201510827335.5A patent/CN106694063A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101587124A (en) * | 2009-07-12 | 2009-11-25 | 宁波大学 | Micro-fluidic chip special for diagnosing syphilis by aid of organic conductor material technology |
| CN102608184A (en) * | 2012-03-08 | 2012-07-25 | 宁波大学 | Sleeved combination type glassy carbon electrode assembly with electric and acoustic dual-excitation function |
| WO2015107014A1 (en) * | 2014-01-15 | 2015-07-23 | Eth Zurich | Acoustophoretic droplet handling in bulk acoustic wave devices |
Non-Patent Citations (2)
| Title |
|---|
| MARCO CECCHINI等: "Acoustic-counterflow microfluidics by surface acoustic waves", 《APPLIED PHYSICS LETTERS》 * |
| 许静芬等: "《物理学》", 30 September 2010 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107199059A (en) | For the classifiable tumor mark joint inspection chip apparatus of women physical examination examination | |
| CN107225003A (en) | The classifiable tumor markers in detecting micro flow control chip device that male is applicable | |
| CN107225002A (en) | The classifiable tumor markers in detecting micro flow control chip device that women is applicable | |
| CN107225005A (en) | Six kinds of classifiable tumor mark multichannels are while detection micro flow control chip device | |
| CN107213925A (en) | Joint-detection male's classifiable tumor mark micro flow control chip device | |
| CN106568952A (en) | Micro-fluidic chip device for simultaneously detecting women's various typical tumor markers | |
| CN107213926A (en) | The micro flow control chip device of ten Five-channel joint-detection Diagnostic Value of Several Serum Tumor Markers | |
| CN107694635A (en) | Six kinds of classifiable tumor mark multichannels while detection micro flow control chip device | |
| CN107694632A (en) | Easily-disassembled male's classifiable tumor markers in detecting chip apparatus | |
| CN106807457A (en) | Various everywoman's co-detections of tumor markers in benign micro flow control chip devices | |
| CN106814184A (en) | The tumor markers joint-detection six-channel microfluidic chip device simplified | |
| CN106694063A (en) | Micro-fluidic chip device used for typical tumor marker joint detection and suitable for males | |
| CN106706913A (en) | Pervasive micro-fluidic chip device for simultaneously detecting multiple tumour markers | |
| CN106694062A (en) | Micro-fluidic chip device for typical tumor marker combined detection applicable for women | |
| CN106694064A (en) | Microfluidic chip device for multi-channel simultaneous detection of six typical tumor markers | |
| CN107694633A (en) | The classifiable tumor markers in detecting micro flow control chip device that women is applicable | |
| CN106563514A (en) | Microfluidic chip apparatus for combined detection of male typical tumor markers | |
| CN106918694A (en) | Using the chip apparatus for joint inspection Diagnostic Value of Several Serum Tumor Markers of hydrophobic substrate | |
| CN106568953A (en) | Microfluidic chip device for detecting multiple tumor markers based on 15-channel joint detection | |
| CN107225004A (en) | General type is used for the micro flow control chip device for detecting Diagnostic Value of Several Serum Tumor Markers simultaneously | |
| CN107694621A (en) | The male tumor mark joint inspection chip apparatus of two kinds of type of drive coupling runnings | |
| CN106563513A (en) | Microfluidic chip device for combined detection of six typical tumor markers | |
| CN107694640A (en) | General type is used for the micro flow control chip device for detecting Diagnostic Value of Several Serum Tumor Markers simultaneously | |
| CN107694648A (en) | The classifiable tumor markers in detecting micro flow control chip device that male is applicable | |
| CN106680349A (en) | Typical tumor marker combined detection chip device for female medical screening |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170524 |