CN106984365A - The multichannel micro-fluidic chip device that a variety of hypotype swine flus are detected simultaneously - Google Patents
The multichannel micro-fluidic chip device that a variety of hypotype swine flus are detected simultaneously Download PDFInfo
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- CN106984365A CN106984365A CN201610065355.8A CN201610065355A CN106984365A CN 106984365 A CN106984365 A CN 106984365A CN 201610065355 A CN201610065355 A CN 201610065355A CN 106984365 A CN106984365 A CN 106984365A
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- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
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- 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
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- 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
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Abstract
The present invention relates to the multichannel micro-fluidic chip device that one kind of multiple hypotype swine flus are detected simultaneously, belong to analysis testing field.The serial problem of substrate physical presence for making hypotype swine flu diagnosis micro-fluidic chip using dimethyl silicone polymer i.e. PDMS that is cheap and easily processing；Its surface of the PDMS material is strongly hydrophobic, and targetedly surface is modified or surface modification, and its effect is difficult to persistently, and this case aims to solve the problem that the serial relevant issues.This case main points are, the selected PDMS with ecosystem surface of substrate, and its neighbor positions attaches installing miniature ultrasonic transducer units in the test liquid stream terminal of the micro-fluidic chip, ultrasonic wave damper is installed at the sample introduction end of the micro-fluidic chip, reach ultrasonic intensity rapid decrement in short distance, and interfacial tension difference, and then the pressure difference formed between the two ends are thus formed at the two ends of the chip, the pressure differential test liquid stream flows along capillary channel to the terminal direction.
Description
Technical field
The present invention relates to the multichannel micro-fluidic chip device that one kind of multiple hypotype swine flus are detected simultaneously, the micro fluidic device is base
The special purpose device of hypotype swine flu antigen is diagnosed in antigen/antibody specific reaction, belongs to analysis testing field.
Background technology
Multichannel micro-fluidic hypotype swine flu diagnostic techniques background, may refer to the patent of invention such as CN 201110311127.1 Shen
Please case.
Only for the microflow control technique overall general picture of itself, it may refer to famous micro-fluidic expert Mr. Lin Ping Cheng and go out not long ago
Monograph " diagram Microfluid based Lab on a chip ", the monograph is published via Science Press, and the monograph is to microflow control technique
Past, now, and, in terms of vision of the future etc., suffer from detail, be deep into long discussion of detail.
So, the Important Problems of this case that to have a talk below concern.
The basic framework of micro-fluidic chip, including it is etched with the substrate of small fluid course and the cover plate fit together therewith,
Small fluid course on the substrate, assembling upper cover plate before, it is apparent on see to be exactly some micro-channels, wait until thereon
After covering cover plate, just real closure forms the small fluid course, and the conduit inner surface of the micro-channel is together with surround this
The part cover plate of micro-channel constitutes described small fluid course together；So, it is clear that this after assembling is completed is small
Fluid course, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, in the micro-channel
The state or property on surface substantially determine the integrality or property of the small fluid course；Therefore say, this is built in base
The inner surface state or inner surface property of micro-channel on piece are key factors；In principle, it is any to keep or protecting substantially
The material of its solid forms is held, can be used to make substrate and cover plate, such as, the material that can act as substrate and cover plate can be with
It is monocrystalline silicon piece, quartz plate, sheet glass, high polymer such as dimethyl silicone polymer, polymethyl methacrylate, makrolon etc.
Deng；Certainly, the selection of substrate and the selection of cover plate be able to can also be differed with identical；From material consumption, manufacture difficulty and
From the point of view of in terms of application popularization prospect etc., between these materials exist not small difference, the especially selection of that substrate, influence compared with
Greatly.
In various substrate making materials, dimethyl silicone polymer, i.e. PDMS, comparatively very easily shaping, so
Substrate on make that micro-channel is extremely simple, and the lower cost for material makes substrate with the polydimethyl siloxane material,
Micro-channel is being suppressed or etched thereon, and is being engaged with the cover plate that the cheap material such as glass or polypropylene or other plastic sheets makes,
It is a kind of more satisfactory selection seemingly；Certainly, patch material can also select to use cheap polydimethyl siloxane material：
So, this substrate selection is the scheme of polydimethyl siloxane material, and material is extremely cheap, makes extremely simple, seems and should also be as
It is extremely easy to popularize, promotes.
But, thing is really not so simple.
First, this polydimethyl siloxane material, that is, the material that the letter PDMS that abridges is referred to, itself are a kind of strong
Hydrophobic material, micro-channel is built on this material, if without being operated for the modified of the micro-channel surface, then,
After overall assembling is completed, that is, cover after cover plate, because the micro-channel its inner surface in structure occupies most liquid circulation
The inner surface in road, then, its strong hydrophobic property of the PDMS micro-channels inner surface, is deciding factor, it can cause class
Be similar to the aqueous solution the fine liquid stream of polar liquid by becoming very difficult, its flow resistance is big, or even general Micropump is all
It is difficult to promote, certainly, if cover plate also selects to use the PDMS material, then, problem is substantially identical, similar；
Therefore, among prior art, modification is modified particular for the micro-channel inner surface on the PDMS material, is necessary
Operation；So, this is pretty troublesome for the modified operation of PDMS micro-channel inner surfacesThat falls nor this problem, structure
Perplex into serious technical, be another problem：PDMS polymer molecules tool inside its body phase of this PDMS material substrate
There are PDMS polymer molecules inside the characteristic for diffusing to the surface, migrating automatically, this substrate body phase to diffuse to the surface, move automatically
The characteristic of shifting, will cause the state after modification by its inner surface of that micro-channel of surface modifying and decorating can not maintain foot
Enough long time, the holding time for micro-channel its inner surface state after that is surface-modified is substantially only sufficient to complete in laboratory
The time of portion's test experiments needs；In other words, by surface modification or the PDMS micro-channel inner surfaces of surface modification, its
The surface state that is formed can not be lasting after modification or after saying modification, but soon automatically tend to or say and become surface again and change
Surface state before property, returns to the strong hydrophobic surface state of that script in the shorter time, then, just think,
Such micro-fluidic chip can largely make, mass storage, be widely popularized, and answer is it is obvious that is, impossible.
Micro-channel on this PDMS material, can not pump similar to the fine liquid stream of polar solvent of the aqueous solution if not doing surface modification
Send and pass through, chip also cannot just be used；And if having done surface modification, the state after its modification can not be persistently kept again, also
Being equally can not popularization and application.
So, how to accomplish that substrate can either be made using cheap PDMS material, and table in the micro-channel can be released
Face decorating state can not persistently, chip can not largely make, largely lay in so that be widely popularized it is such a make this area it is numerous specially
The puzzlement that industry personnel are entangled with for a long time, the highly difficult problem that exactly one its obvious technology barrier can not despise.
Be present many year in the highly difficult problem, so far, not yet properly settled.
Second, the PDMS material of non-surface modification, above it is stated that, its surface is strongly hydrophobic, this strong hydrophobic
Material surface and also another problem, that is, this strong hydrophobic PDMS surfaces can adsorb large biological molecule, and
And, these adsorbed large biological molecules can also further depression further on PDMS surfaces, gradually fall into gradually deep, directly
It is trapped in heavy within the body phase of PDMS substrates, in fact, this process is partly also due to inside PDMS material body phase
Polymer molecule, which has, to be diffused to the surface, caused by travel motion；Such case, can also be explained from another angle, i.e.
Continuously from inside PDMS body phases to its diffusion into the surface, migration those polymer molecules, its result moved, be by
Gradually those are involved within the body phase of PDMS substrates by the large biological molecule of adsorption, briefly, these are inhaled
Attached large biological molecule is exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up large biological molecule
Phenomenon, the influence caused by it necessarily causes the severe deviations of all kinds of test data of experiment for being related to large biological molecule.
As described above, be the problem of PDMS substrates, its not only adsorption large biological molecule, and swallow up large biological molecule,
So, as the large biological molecule of experiment test object, its disappearance will not stop because the absorption of surface saturation, but, no
It is disconnected adsorbed, also constantly swallowed up.
On PDMS substrates in related experiment test process its body phase constantly swallow up test associated biomolecule macromolecular phenomenon, separately
It is to say that one kind, which is explained, there are substantial amounts of Minute pores in PDMS body phases, and associated biomolecule macromolecular is by after adsorption, depression
Into these Minute pores, and then swallowed up；However, inventor thinks, those can allow the air point of miniature scale
Son squeezes into the Minute pores therebetween, and being not equal to them also can directly allow that the large biological molecule of relative large scale enters, and two
Person's difference on yardstick is huge, must not make sweeping generalizations.Explanation is bypassed, in any case, the biology of object is analyzed as dependence test
Macromolecular is adsorbed by PDMS substrate micro-channels inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is known objective
The phenomenon of presence.
, can be from containment PDMS surfaces to life in order to prevent this PDMS substrate bodies relative to the effect of swallowing up of large biological molecule
The absorption of thing macromolecular is addressed, and method is chemically modified modification aiming at the PDMS material surface, for
For PDMS is the situation of substrate material, modification exactly is chemically modified to the surface of described micro-channel part, by changing
The micro-channel inner surface of modification is learned, its absorption to large biological molecule can be contained, and then avoid large biological molecule quilt
PDMS substrate body phases are swallowed up；But, or that old problem, that is, the chemical modification on PDMS material surface changes
Surface state after property can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface automatically,
The process of migration, soon can become that micro-channel inner surface state being modified by surface chemical modification again script strong and dredge
Water and the state of strong adsorption large biological molecule, in other words, no matter how professionals in the field turn from side to side, the PDMS
Its micro-channel inner surface of substrate is always rapidly to strong hydrophobic surface state evolution.
So, how can either obtain that PDMS material price is extremely cheap, substrate makes extremely easy benefit, can reach again
Growth stage contains absorption process of the PDMS substrate micro-channel inner surfaces to large biological molecule, and then prevents PDMS substrate body phases
The effect of swallowing up to large biological molecule so that related chip manufactured goods are able to maintain that a prolonged enough, rational shelf-life,
It is exactly a very intractable problem.The problem makes the numerous specialties in this area as another problem addressed above, equally
Personnel are entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise.The hardly possible
Also be present many year in topic, so far, also not yet properly settled.
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 used into multichannel micro-fluidic chip field applied to hypotype swine flu diagnosis, form a kind of
Multichannel micro-fluidic device is used in new hypotype swine flu diagnosis.
The present invention solves the technical problem by following scheme, and the device that the program is provided is that one kind of multiple hypotype swine flus are same
When the multichannel micro-fluidic chip device that detects, the structure of the micro fluidic device includes multichannel micro-fluidic chip, the micro-fluidic core
The structure of piece includes the substrate and cover plate of installing bonded to each other together, and the substrate and cover plate are plate object or tablet, are somebody's turn to do
That face towards the cover plate of substrate contain via mould pressing process or etching technics formation channel structure, the substrate also contain with
The channel structure is connected and pierces the window knot via the formation of mould pressing process, etching technics or simple drilling technology of the substrate
Structure, substrate bonded to each other being installed together has been built into containing pipeline configuration and the liquid pool being attached thereto jointly with the cover plate
The micro-fluidic chip of structure, the locations of structures of the pipeline is located at the substrate and cover plate interface zone bonded to each other, the window its
Side 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
Quantity is three, and its locations of structures of two liquid pools therein is located at the sample introduction end of the micro-fluidic chip, its knot of a remaining liquid pool
Structure position is located at the terminal of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, and the terminal and the sample introduction end are mutual
It is remote, one end of the pipeline via be similarly positioned in the manifold shape turnout of the interface zone bonded to each other respectively with positioned at sample introduction end
The Liang Ge liquid pools UNICOM, the other end of the pipeline and a remaining liquid pool for the terminal positioned at the micro-fluidic chip join
It is logical, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode and reference electrode is described
Working electrode is by conductive electrode and the gold size for having embedded hypotype swine flu specific antibody being attached on the conductive electrode
Sensitive membrane is constituted, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of three lateral parallel connections,
The quantity of the working electrode is three, and the installation position of three working electrodes is located in three laterals respectively, with
And, the specific antibody in the sensitive membrane structure of its top layer gold size of three working electrodes is respectively can be special to hypotype swine flu antigen
Property combine three kinds of hypotype swine flu antibody materials, three kinds of antibody materials are hypotype swine flu specific antibody H respectively1N1、H3N2
And H1N2, its material of the working electrode is gold material or thermal decomposition conducting polymer material, and its pattern of the working electrode is in
Existing sheet or thread, emphasis is that its material of the substrate 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 micro fluidic device also includes miniature ultrasonic transducer units, and, higher-order of oscillation electricity
Signal transmission cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable link together, and this is micro-
Type ultrasonic transducer is installed in the position of the cover plate of the micro-fluidic chip or the neighbouring terminal of substrate with attaching；This is miniature super
Its major function of acoustic wave transducer is that in the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it reduces sample
Interfacial tension between the inwall of solution and the pipeline, can be compatible, also, utilizes the sample introduction end and the end
Difference in the distance between end and the miniature ultrasonic transducer units installation position difference and its ultrasonic intensity experienced,
Difference between its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension, the micro-fluidic chip two ends it
Between interfacial tension difference can form pressure gap between the two ends of the micro-fluidic chip, the pressure gap can drive sample molten
Liquid is to the end flow；Its function of the miniature ultrasonic transducer units is also contained in sample including being checked with its ultrasonic wave launched
Its absorption on the inner surface of pipeline of some large biological molecules, and then check the substrate of the dimethyl silicone polymer material its body
With respect to the effect of swallowing up of the large biological molecule；Its function of the substrate of the dimethyl silicone polymer material includes and cover plate and work electricity
Pole and the micro-fluidic chip is together built to electrode and reference electrode, the base of the dimethyl silicone polymer material that is soft and having elasticity
Piece its function also includes, with its property to the strong absorption of ultrasonic wave, ultrasonic wave being absorbed strongly, and thereby micro-fluidic at this
The chip terminal is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end；And, ultrasonic wave
Damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；Its material of the ultrasonic wave damper be microcellular rubber,
Sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, the inner side of each clamping limb
Face is relative with the medial surface of another clamping limb, and the medial surface of one of clamping limb is close to the sample introduction end of the micro-fluidic chip,
The medial surface of another clamping limb is close to the ultrasonic wave damper, the elastic clip entering the micro-fluidic chip with its gripping strength
Sample end and the ultrasonic wave damper are clipped together bonded to each otherly, the ultrasonic wave damper with its material brought to ultrasonic wave energy
The strong consumption of amount, is further supported within micro-fluidic chip terminal to the limited short distance between the sample introduction end
The rapid decrement of ultrasonic intensity is realized, and thereby further expands described its interfacial tension of sample introduction end and its interface of the terminal
Difference between power.
The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and hypotype swine flu specific antibody solution uniformly, is used
Point sample instrument point sample is coated on specified structure position, and forms its drying and forming-film.Hypotype swine flu in the gold size sensitive membrane
Specific antibody is the hypotype swine flu antibody of horseradish peroxidase or glucose oxidase mark, the gold size sensitive membrane
It has been included as fixing above-mentioned each hypotype swine flu specific antibody and introducing complementary medium therein, the complementary medium is for example
Chitosan, cellulose acetate, gelatin be therein a kind of or their mixture.
The pipeline and the lateral and the manifold shape turnout in the microfluidic chip structure, its internal diameter chi
It is very little to may each be arbitrarily selected size, still, use the consideration in terms of prepare liquid sample and reduction reagent loss less for trying one's best,
The passage of capillary level, the capillary level are preferably selected in the pipeline and the lateral and the manifold shape turnout
Passage imply that its internal diameter passage suitable with the internal diameter of the capillary on ordinary meaning.Its inner passage of capillary it is transversal
Face shape can be arbitrary shape, the shape of cross section is for example circular, oval, square, rectangle, bar shaped, certainly
Can be arbitrarily exist bending it is linear, also, the capillary interior shape with the extension of pipeline, different parts
Shape of cross section 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 may each be any choosing
Fixed shape, the arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..It is described to electricity
The art-recognized meanings of pole and the reference electrode vocabulary of itself are known.
It is related to several liquid pools in this case microfluidic chip structure, the liquid pool is the pond shape or 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..The size of the liquid pool can be arbitrarily selected
Size, still, in order to use prepare liquid sample and reduction reagent loss less as far as possible, the liquid pool is preferably capable of and capillary
The liquid pool of the microminiature of matching.
It is public only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field
Know.
Various sizes, variously-shaped ultrasonic transducer are commercially available；Commercially available miniature ultrasonic transducer units its sizes can be with
It is small to the magnitude only calculated with millimeter.
Only with regard to miniature ultrasonic transducer units its technique for fixing on general industry application solid body surface itself and
Speech, is known general technology for the professional in ultrasonic technology field.This case is not to this expansion superfluous words.
Only with regard to naked PDMS substrates itself micro-channel molding or lithographic technique for, be open-and-shut known technology；Together
Sample, 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
Its other end of cable can be connected with the higher-order of oscillation electric signal generator.
The involved higher-order of oscillation electric signal generator technology of itself, for the professional in ultrasonic technology field, be
It is simple and known；The higher-order of oscillation electric signal generator can be customized to ultrasonic instrument specialized factory.
The preferred scope of its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units be between 2 milliwatts and 2000 milliwatts it
Between；The preferred scope of the frequency of its ultrasonic wave operationally launched of the miniature ultrasonic transducer units be between 100KHz with
Between 12MHz.
This case device can further include some annexes, the annex such as multiple tracks electrochemical workstation etc., institute certainly
The art-recognized meanings for stating multiple tracks electrochemical workstation are known.Each working electrode for being related in this case microfluidic chip structure and
, can be respectively via corresponding special the corresponding interface got lines crossed with the multiple tracks electrochemical workstation to electrode and reference electrode etc.
Coupled.It is described that special to get lines crossed be for each the corresponding interface of each electrode and the multiple tracks electrochemical workstation is carried out into phase
The private cable being mutually coupled with.The micro-fluidic chip in this case device, its structure can also include micro-valve, the number of the micro-valve
Amount is not limited, according to actual needs, and the micro-valve can be installed in any required position installed in the microfluidic chip structure；
The word of micro-valve one is for the professional of micro fluidic chip technical field, and the art-recognized meanings of itself are known；The micro-valve
The manufacturing technology of itself and the use of technology is also known；The component that the micro-valve is not required.
The diameter of the working electrode can allow to be that any setting is easily installed the suitable diameter used, it is however recommended to
Or say preferred its scope of the diameter between 0.1 micron to 2000 microns；The length of the working electrode can permit
Permitted to be that any setting is easily installed the length used, it is however recommended to or to say preferred its scope of the length be at 1 micron
To between 15000 microns.
The gold size for being installed in the working electrode surface layer by spraying or point sample instrument point sample or the coating of other appropriate process is quick
Feel film, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness, still, push away
Preferred thickness is between 10 nanometers and 200 nanometers in other words for the thickness recommended.
The cover plate in chip structure, its material can allow to be any electrical insulating property material, for example：Polypropylene, glass
Glass, polymethyl methacrylate, dimethyl silicone polymer, etc., in order to make smaller size of micro-fluidic chip, such as do
Realized into the micro-fluidic chip of only 2.0 centimetres to 3.0 centimetres of super-small of length, and in the extremely short distance to ultrasonic wave
Extremely fast decay, can preferably dimethyl silicone polymer be used as cover plate.Certainly, selected on large-sized micro-fluidic chip
It is used as the cover plate using dimethyl silicone polymer, is also that this case technical scheme is allowed.
Positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal this is remaining
Air line distance between one liquid pool can be arbitrarily selected suitable distance as needed, and still, the preferred value of the distance is
Between 3 centimetres and 7 centimetres.
Described its thickness of cover plate and substrate can allow be any setting be easy to assembling thickness, the thickness of recommendation or say preferably
Thickness be between 1.0 millimeters and 5.0 millimeters.Less thickness is conducive to saving material.
Described its size of ultrasonic wave damper is not limited, and described its length of ultrasonic wave damper, width, thickness may each be basis
Need the arbitrary size of setting.
It is known in field of rubber technology only for the word of microcellular rubber one art-recognized meanings of itself.
The microcellular rubber is commercially available.
It is known in field of rubber technology only for the word of sponge rubber one art-recognized meanings of itself.
The sponge rubber is commercially available.
It is known in technical field of macromolecules only for the word of microporous polyurethane elastomer one art-recognized meanings of itself.
The polyurethane micropore elastomer material is commercially available.
The microcellular rubber preferred microporous silicon rubber or micropore fluorubber.
It is known in field of rubber technology only for the word of micropore silicon rubber one art-recognized meanings of itself.
The microporous silicon Rubber market is on sale.
It is known in field of rubber technology only for the word of micropore fluorubber one art-recognized meanings of itself.
The micropore fluorubber is commercially available.
The word of elastic clip one art-recognized meanings of itself are known.
The elastic clip is commercially available.
The application method of this case micro-fluidic chip：
Proposed first based on this case and the first public New stream driving principle, its application running of this case micro-fluidic chip
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 micro-fluidic chip two ends caused by the ultrasonic wave, drives liquid
Stream flows in the capillary channel of the triple channel micro-fluidic chip, using multi-channel electrochemical analyzer device respectively to three kinds of hypotypes
Swine flu diagnostic antigen is detected.
The specific detection of this case micro-fluidic chip is as follows using step：
1st, blood serum sample liquid is added in micro-pipe road, under ultrasonic wave driving, various hypotype swine flu antigen molecules are each
In passage on electrode surface gold size sensitive membrane embed corresponding horseradish peroxidase-labeled hypotype swine flu specific antibody
Capture.
2nd, the hypotype swine flu antigen in the hypotype swine flu specific antibody and blood serum sample of horseradish peroxidase-labeled is formed
Immune complex.
3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, using the above-mentioned reaction of amperometric detection
Caused curent change, is derived from the species and content of various analytes.
4th, result is subjected to comprehensive analysis, comprehensive diagnos is carried out to hypotype swine flu antigen.
Changed it is an advantage of the invention that installing miniature ultrasonic in its close position attaching of the terminal of the micro-fluidic chip
Can device, it is launched using the miniature ultrasonic transducer units low-power, the ultrasonic wave of high-frequency band so that without coming to the surface
The compatibility learned between strong hydrophobic its tube wall of micro-fluidic chip internal pipeline and the test object aqueous solution of modification significantly increases
Plus, this is test liquid stream by there is provided a realistic possibility；Meanwhile, using dimethyl silicone polymer substrate its to ultrasound
The strong absorbability of ripple, in shorter distance, it is, from the terminal to only several centimeters the sample introduction end
In the very short distance of yardstick, reach the rapid decrement of ultrasonic intensity, thereby cause institute at the two ends of the micro-fluidic chip
The difference of interfacial tension is stated, and then, utilize the pressure between its two ends for being formed of the difference of the interfacial tension between the two ends
Difference, driving test liquid stream flows in the strong hydrophobic capillary channel of such a script to the terminal direction.By this
Case liquid stream drive scheme, entirely without any come to the surface must be carried out to the substrate and its internal pipeline of the dimethyl silicone polymer material
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 Micropump in meaning of uniting etc；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 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 the type for belonging to 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 facilitating what the Reversible binding between antigen, antibody react quickly to reach, this causes correlation certainly
Test operation can be with than the completion of faster speed.
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 to exist, then, the dimethyl silicone polymer
Its body phase interior polymer molecule of substrate constantly diffuses to the surface automatically, migrate caused by it to surface chemical modification layer or
The damaging influence of chemically modified layer is also just not present.
The technical scheme of this case has dissolved its application related one to dimethyl silicone polymer substrate addressed above totally
Row technical barrier.Based on this case scheme, this kind very cheap polydimethyl siloxane material is just possible in micro-fluidic chip system
Standby, production, using etc. field play bigger effect.
This case its installation position is located at the ultrasonic wave damper at the sample introduction end, from its terminal of this case micro-fluidic chip to
Said on the sport technique segment that ultrasonic intensity rapid decrement is realized in the such short distance in sample introduction end, its effect of the ultrasonic wave damper is suitable
In the size expansion device of micro-fluidic chip, in other words, the ultrasonic wave damper its function as and significantly extend miniflow
Its terminal of chip is controlled the distance between to sample introduction end, is the equal of from several centimetres of extension of script to more than ten centimetres of length
Or twenties centimetres of length or longer length, so so that described terminal to the ultrasonic wave between sample introduction end in short distance
The sport technique segment of intensity rapid decrement can relatively easily be reached, also, the size expansion device namely the ultrasonic wave damper
Demolition, installation are convenient, it is important that it can also be reused.
Brief description of the drawings
Fig. 1 is the schematic diagram of this case micro fluidic device embodiment chip part construction, it is shown that this structure is bowed
Do not depicted in the structural form of chip internal pipeline and each electrode and each related liquid pool under angle, the figure described miniature super
Acoustic wave transducer and other annexes.
Fig. 2 is its rough outside side view of this case micro fluidic device.
In figure, 1,2,8 be the different liquid pool of three installation positions respectively, and 3 be manifold shape turnout, and 4,9,12 are respectively
Installation position is different but three laterals parallel with one another for forming UNICOM's structure in parallel, and 5 be its that be installed in lateral 4
Specific antibody material in the sensitive membrane structure of top layer gold size is hypotype swine flu specific antibody H1N1Working electrode, 10 are
The specific antibody material being installed in the sensitive membrane structure of its top layer gold size in lateral 9 is anti-for hypotype swine flu specificity
Body H3N2Working electrode, 11 be the specific antibody thing in the sensitive membrane structure of its top layer gold size being installed in lateral 12
Matter is hypotype swine flu specific antibody H1N2Working electrode, 6 be that, to electrode, 7 be reference electrode, and 13 be poly dimethyl silicon
The substrate of oxygen alkane material, 14 be cover plate, and 15 be higher-order of oscillation electric signal transmission cable, and 16 be miniature ultrasonic transducer units, 17
It is the sample introduction end of the micro-fluidic chip, 18 be the terminal of the micro-fluidic chip；Arrow sign in legend should
Micro-fluidic chip its in actual motion, by pressure at two ends difference drive, the flow direction of its test liquid stream.
Embodiment
In this case that Fig. 1 and Fig. 2 are shown embodiment, the structure of the micro fluidic device includes multichannel micro-fluidic chip,
The structure of the micro-fluidic chip includes the substrate 13 and cover plate 14 of installing bonded to each other together, the substrate 13 and cover plate 14
It is plate object or tablet, that face towards the cover plate 14 of the substrate 13 is contained via mould pressing process or etching technics shape
Into channel structure, the substrate 13 also containing be connected with the channel structure and pierce the substrate 13 via mould pressing process, quarter
Etching technique or the window structure of simple drilling technology formation, substrate 13 bonded to each other being installed together and the cover plate 14 are common
The micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto is built into, the locations of structures of the pipeline is located at the base
Piece 13 and the cover plate 14 interface zone bonded to each other, its side of the window is blocked by the cover plate 14 and opposite side is opened, should
The locations of structures of window is exactly the locations of structures of the liquid pool, and the quantity of the liquid pool is three, and three liquid pools are liquid pool respectively
1st, liquid pool 2, liquid pool 8, two liquid pools therein are the sample introduction of liquid pool 1 and its locations of structures of liquid pool 2 positioned at the micro-fluidic chip
End, a remaining liquid pool is that liquid pool 8 its locations of structures is located at when the actual sample introduction of the micro-fluidic chip is tested liquid flow in its chip
Dynamic terminal 18, the terminal 18 is located remotely from each other with the sample introduction end 17, and one end of the pipeline is bonded to each other via this is similarly positioned in
The manifold shape turnout 3 of interface zone be liquid pool 1 and the UNICOM of liquid pool 2 with two liquid pools positioned at sample introduction end 17 respectively, should
A remaining liquid pool for the terminal 18 of the other end of pipeline with being located at the micro-fluidic chip is the UNICOM of liquid pool 8, and,
The working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode and reference electrode, the working electrode by
Conductive electrode and the gold size sensitive membrane for having embedded hypotype swine flu specific antibody being attached on the conductive electrode are constituted,
The construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of three lateral parallel connections, the working electrode
Quantity be three, the installation positions of three working electrodes is located in three laterals respectively, and, three works
The specific antibody made in the sensitive membrane structure of its top layer gold size of electrode is can be specifically bound to hypotype swine flu antigen three respectively
Hypotype swine flu antibody materials are planted, three kinds of antibody materials are hypotype swine flu specific antibody H respectively1N1、H3N2And H1N2, tool
For body expansion, 5 be that specific antibody material in the sensitive membrane structure of its top layer gold size being installed in lateral 4 is hypotype
Swine flu specific antibody H1N1Working electrode, during 10 are the sensitive membrane structure of its top layer gold size being installed in lateral 9
Specific antibody material be hypotype swine flu specific antibody H3N2Working electrode, 11 are installed in lateral 12
Specific antibody material in the sensitive membrane structure of its top layer gold size is hypotype swine flu specific antibody H1N2Working electrode, it is described
Its material of working electrode is gold material or thermal decomposition conducting polymer material, and sheet or silk is presented in its pattern of the working electrode
Shape, emphasis is, its material of the substrate 13 is dimethyl silicone polymer material, and its surface of substrate 13 is the table of primary form
Face, the surface of the primary form its be intended to refer to the material not by any surface chemical modification or any surface chemical modification
The surface of the primary form of matter, the structure of the micro fluidic device also includes miniature ultrasonic transducer units 16, and, the higher-order of oscillation
Electric signal transmission cable 15, one end of the higher-order of oscillation electric signal transmission cable 15 is connected with the miniature ultrasonic transducer units 16
Together, the miniature ultrasonic transducer units 16 are installed in cover plate 14 or the neighbouring institute of substrate 13 of the micro-fluidic chip with attaching
State the position of terminal 18；Its major function of the miniature ultrasonic transducer units 16 be in the actual sample introduction test of micro-fluidic chip,
The ultrasonic wave launched using it reduces the interfacial tension between sample solution and the inwall of the pipeline, can be compatible,
Also, utilize the distance between the sample introduction end 17 and the terminal 18 and the installation position of miniature ultrasonic transducer units 16
Difference in difference and its ultrasonic intensity experienced, its interfacial tension of sample introduction end 17 described in induced synthesis and the end
Hold the interfacial tension difference between the difference between 18 its interfacial tension, the micro-fluidic chip two ends can be in the micro-fluidic chip
The two ends between form pressure gap, the pressure gap can drive sample solution to be flowed to the terminal 18；The miniature ultrasonic
Wave transducer 16 its function also include with its ultrasonic wave launched check large biological molecule contained in sample its in the pipe
Absorption on road inner surface, and then check the substrate 13 of the dimethyl silicone polymer material its body phase the large biological molecule is gulped down
Do not act on；Its function of the substrate 13 of the dimethyl silicone polymer material includes and cover plate 14 and working electrode 5,10,11
And the micro-fluidic chip is together built to electrode 6 and reference electrode 7, the dimethyl silicone polymer material that is soft and having elasticity
Substrate 13 its function also includes, with its property to the strong absorption of ultrasonic wave, ultrasonic wave being absorbed strongly, and thereby at this
The micro-fluidic chip terminal 18 is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 17；
And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；Its material of the ultrasonic wave damper
It is microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, each
The medial surface of clamping limb is relative with the medial surface of another clamping limb, and the medial surface of one of clamping limb is close to the micro-fluidic core
The sample introduction end 17 of piece, the medial surface of another clamping limb is close to the ultrasonic wave damper, and the elastic clip will with its gripping strength
The sample introduction end 17 of the micro-fluidic chip and the ultrasonic wave damper are clipped together bonded to each otherly, and the ultrasonic wave damper is with its material
The strong consumption to ultrasonic energy that matter is brought, further supports that the terminal 18 arrives the sample introduction in the micro-fluidic chip
The rapid decrement of ultrasonic intensity is realized within limited short distance between end 17, and thereby further expands the sample introduction end
Difference between 17 its interfacial tension and the terminal 18 its interfacial tension.The ultrasonic wave damper is depicted without in legend, is schemed
The elastic clip is also depicted without in example.
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.
Miniature ultrasonic transducer units 16 and higher-order of oscillation electric signal transmission cable 15 are depicted without in Fig. 1；Also, Fig. 1
And the associate members such as the higher-order of oscillation electric signal generator and multiple tracks electrochemical workstation are depicted without in Fig. 2.
Involved miniature ultrasonic transducer units 16 are commercially available；It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal transmission cable 15 is commercially available；It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；It can also be customized to relevant manufacturers.
Each working electrode in this example structure and electrode and reference electrode via each special cable or can be said respectively
Get lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as annex or saying interface connection of getting lines crossed.
Claims (10)
1. the multichannel micro-fluidic chip device that many kinds of hypotype swine flus are detected simultaneously, the structure of the micro fluidic device includes multichannel
Micro-fluidic chip, the structure of the micro-fluidic chip includes the substrate and cover plate of installing bonded to each other together, the substrate and cover plate
It is plate object or tablet, the groove via mould pressing process or etching technics formation is contained in that face towards the cover plate of the substrate
Road structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or simply
The window structure of drilling technology formation, substrate bonded to each other being installed together has been built into jointly with the cover plate contains pipeline knot
The micro-fluidic chip of structure and the liquid pool structure being attached thereto, the locations of structures of the pipeline is located at the substrate and the cover plate is bonded to each other
Interface zone, its side of the window by the cover plate block and opposite side open, the locations of structures of the window is exactly the liquid pool
Locations of structures, the quantity of the liquid pool is three, and its locations of structures of two liquid pools therein is located at the sample introduction end of the micro-fluidic chip,
Its locations of structures of a remaining liquid pool is located at the terminal of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, should
Terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is via the manifold shape turnout for being similarly positioned in the interface zone bonded to each other
Respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline should with the terminal positioned at the micro-fluidic chip
A remaining liquid pool UNICOM, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode with
And reference electrode, the working electrode by conductive electrode and be attached on the conductive electrode to have embedded hypotype swine flu special
The gold size sensitive membrane of heterogenetic antibody is constituted, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by three branches
Pipeline parallel connection is constituted, and the quantity of the working electrode is three, and the installation position of three working electrodes is located at described three respectively
In lateral, and, the specific antibody in the sensitive membrane structure of its top layer gold size of three working electrodes is to hypotype pig respectively
Three kinds of hypotype swine flu antibody materials that influenza antigens can be specifically bound, three kinds of antibody materials are that hypotype swine flu is special respectively
Property antibody H1N1、H3N2And H1N2, its material of the working electrode is gold material or thermal decomposition conducting polymer material, the work
Make electrode its pattern presentation sheet or thread, it is characterised in that its material of the substrate is dimethyl silicone polymer material, the substrate
Its surface is the surface of primary form, the surface of the primary form its be intended to refer to not by any surface chemical modification or appoint
The surface of the primary form of the material of what surface chemical modification, the structure of the micro fluidic device also includes miniature ultrasonic transducing
Device, and, higher-order of oscillation electric signal transmission cable, one end and the miniature ultrasonic of the higher-order of oscillation electric signal transmission cable are changed
Energy device is linked together, and the miniature ultrasonic transducer units are installed in described in the cover plate of the micro-fluidic chip or the neighbouring of substrate with attaching
The position of terminal；Its major function of the miniature ultrasonic transducer units is, in the actual sample introduction test of micro-fluidic chip, to be sent out using it
The ultrasonic wave penetrated reduces the interfacial tension between sample solution and the inwall of the pipeline, can be compatible, also, utilizes
The distance between the sample introduction end and the terminal and miniature ultrasonic transducer units installation position difference and its experienced
Ultrasonic intensity on difference, the difference between its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension
Different, the interfacial tension difference between the micro-fluidic chip two ends can form pressure differential between the two ends of the micro-fluidic chip
Different, the pressure gap can drive sample solution to the end flow；Its function of the miniature ultrasonic transducer units also includes with its institute
The ultrasonic wave of transmitting checks in sample contained large biological molecule its absorption on the inner surface of pipeline, and then checks this and gather
Swallow up effect of its body phase of the substrate of dimethyl siloxane material to the large biological molecule；The base of the dimethyl silicone polymer material
Its function of piece includes with cover plate and working electrode and electrode and reference electrode is together built the micro-fluidic chip, and softness simultaneously has elasticity
The substrate of the dimethyl silicone polymer material its function also include, with its property to the strong absorption of ultrasonic wave, carrying out ultrasonic wave
It is strong to absorb, and thereby realize that ultrasonic wave is strong within micro-fluidic chip terminal to the limited short distance between the sample introduction end
The rapid decrement of degree；And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；The ultrasound
Its material of ripple damper is microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two
Individual clamping limb, the medial surface of each clamping limb is relative with the medial surface of another clamping limb, and the medial surface of one of clamping limb is tight
Close to the sample introduction end of the micro-fluidic chip, the medial surface of another clamping limb is close to the ultrasonic wave damper, and the elastic clip is with it
Gripping strength by the sample introduction end of the micro-fluidic chip and the ultrasonic wave damper it is bonded to each other clip together, the ultrasonic wave damper
The strong consumption to ultrasonic energy brought with its material, further supports that the terminal is entered to this in the micro-fluidic chip
The rapid decrement of ultrasonic intensity is realized within limited short distance between sample end, and thereby further expand the sample introduction end its
Difference between interfacial tension and the terminal its interfacial tension.
2. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 are detected simultaneously, its feature exists
In the pipeline and the lateral and the manifold shape turnout are capillary channel.
3. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 are detected simultaneously, its feature exists
In, the thermal decomposition conducting polymer be by polyimides or polyacrylonitrile be heat-treated through anoxybiotic after the conductive material that is formed.
4. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 are detected simultaneously, its feature exists
In, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the length of the working electrode
Degree is between 1 micron to 15000 microns.
5. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 are detected simultaneously, its feature exists
In the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 are detected simultaneously, its feature exists
In its material of the cover plate in structure is dimethyl silicone polymer material.
7. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 are detected simultaneously, its feature exists
In, positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal this remaining one
Air line distance between individual liquid pool is between 3 centimetres and 7 centimetres；The cover plate in structure and substrate its thickness are between 1.0
Between millimeter and 5.0 millimeters.
8. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 are detected simultaneously, its feature exists
In the microcellular rubber is micropore silicon rubber or micropore fluorubber.
9. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 are detected simultaneously, its feature exists
Also include higher-order of oscillation electric signal generator in the structure of, the micro fluidic device, its is another for the higher-order of oscillation electric signal transmission cable
One end is connected with the higher-order of oscillation electric signal generator.
10. the multichannel micro-fluidic chip device that a variety of hypotype swine flus according to claim 1 are detected simultaneously, its feature exists
In its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 2 milliwatts and 2000 milliwatts, the miniature ultrasonic
The frequency of its ultrasonic wave operationally launched of wave transducer is between 100KHz and 12MHz.
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| CN201610065355.8A CN106984365A (en) | 2016-01-20 | 2016-01-20 | The multichannel micro-fluidic chip device that a variety of hypotype swine flus are detected simultaneously |
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