CN106990240A - Cheap micro fluidic device is used in the cholera diagnosis for relying on interfacial characteristics to carry out liquid stream driving - Google Patents
Cheap micro fluidic device is used in the cholera diagnosis for relying on interfacial characteristics to carry out liquid stream driving Download PDFInfo
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- CN106990240A CN106990240A CN201610065951.6A CN201610065951A CN106990240A CN 106990240 A CN106990240 A CN 106990240A CN 201610065951 A CN201610065951 A CN 201610065951A CN 106990240 A CN106990240 A CN 106990240A
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Abstract
Cheap micro fluidic device is used the present invention relates to a kind of cholera for relying on interfacial characteristics to carry out liquid stream driving diagnosis, belongs to analysis testing field.There is serial problem with dimethyl silicone polymer i.e. PDMS that is cheap and easily processing to make the substrate of cholera diagnosis micro-fluidic chip；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 is thus formed at the two ends of the chip, the interfacial tension difference causes the two ends to form pressure differential, and the pressure differential drives test liquid stream to be flowed along capillary channel to the terminal direction.
Description
Technical field
Cheap micro fluidic device is used the present invention relates to a kind of cholera for relying on interfacial characteristics to carry out liquid stream driving diagnosis, the micro-fluidic dress
Put is, come the special purpose device of cholera diagnosis antigen, to belong to analysis testing field based on antigen/antibody specific reaction.
Background technology
The micro-fluidic cholera diagnostic techniques background of associated multi-channel, may refer to the grade applications for a patent for invention of CN 200910150930.4
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 cholera diagnosis, formed a kind of new
Multichannel micro-fluidic device is used in cholera diagnosis.
The present invention solves the technical problem by following scheme, and the device that the program is provided is that a kind of support interfacial characteristics is carried out
The cheap micro fluidic device of cholera diagnosis of liquid stream driving, the structure of the micro fluidic device includes multichannel micro-fluidic chip, and this is micro-
The structure of fluidic chip includes the substrate and cover plate of installing bonded to each other together, and the substrate and cover plate are plate object or sheet
The channel structure via mould pressing process or etching technics formation is contained in thing, that face towards the cover plate of the substrate, and the substrate is also
Contain the window via the formation of mould pressing process, etching technics or simple drilling technology for being connected and piercing the substrate with the channel structure
Mouth structure, substrate bonded to each other being installed together and the cover plate have been built into containing pipeline configuration and have been attached thereto jointly
The micro-fluidic chip of liquid pool 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 of mouth 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
The quantity in pond is three, and its locations of structures of two liquid pools therein is located at the sample introduction end of the micro-fluidic chip, a remaining liquid pool
Its locations of structures is located at the terminal 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 via be similarly positioned in the manifold shape turnout of the interface zone bonded to each other respectively with positioned at sample introduction
The Liang Ge liquid pools UNICOM at end, the other end of the pipeline and a remaining liquid pool for the terminal positioned at the micro-fluidic chip
UNICOM, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode and reference electrode, institute
State working electrode sensitive by conductive electrode and the gold size for having embedded cholera specific antibody being attached on the conductive electrode
Film is constituted, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of four lateral parallel connections, described
The quantity of working electrode is four, and the installation position of four working electrodes is located in four laterals respectively, and,
Specific antibody in the sensitive membrane structure of its top layer gold size of four working electrodes can be specifically bound to cholera antigen respectively
Four kinds of cholera antibody materials, four kinds of antibody materials are cholera TP0821 antibody and cholera TP0319 antibody and suddenly respectively
Random TP0624 antibody and cholera O139 mycoprotein antibody, its material of the working electrode are that gold material or thermal decomposition are led
Sheet or thread is presented in electric macromolecule material, its pattern of the working electrode, and emphasis is that its material of the substrate is poly dimethyl silicon
Oxygen alkane material, its surface of the substrate is the surface of primary form, the surface of the primary form its be intended to refer to not by any
The surface of the primary form of surface chemical modification or the material of any surface chemical modification, the structure of the micro fluidic device also includes
Miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, one end of the higher-order of oscillation electric signal transmission cable with
The miniature ultrasonic transducer units link together, the miniature ultrasonic transducer units attach be installed in the micro-fluidic chip cover plate or
The position of the neighbouring terminal of substrate；Its major function of the miniature ultrasonic transducer units is in the actual sample introduction test of micro-fluidic chip
When, the ultrasonic wave launched using it reduces the interfacial tension between sample solution and the inwall of the pipeline, can phase
Hold, also, using the distance between the sample introduction end and the terminal and miniature ultrasonic transducer units installation position difference with
And its difference on the ultrasonic intensity experienced, its interfacial tension of sample introduction end described in induced synthesis and its interface of the terminal
Interfacial tension difference between difference between power, the micro-fluidic chip two ends can between the two ends of the micro-fluidic chip shape
Into pressure gap, the pressure gap can drive sample solution to the end flow；Its function of the miniature ultrasonic transducer units is also wrapped
Include the ultrasonic wave launched with it and check in sample contained large biological molecule its absorption on the inner surface of pipeline, and then
Check swallow up effect of its body phase of the substrate of the dimethyl silicone polymer material to the large biological molecule；The dimethyl silicone polymer
Its function of the substrate of material includes with cover plate and working electrode and together builds the micro-fluidic chip to electrode and reference electrode, soft
And have the substrate of the dimethyl silicone polymer material its function of elasticity and also include with its property to the strong absorption of ultrasonic wave, to super
Sound wave is absorbed strongly, and is thereby realized within micro-fluidic chip terminal to the limited short distance between the sample introduction end
The rapid decrement of ultrasonic intensity；And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；
Its material of the ultrasonic wave damper is microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force
Accompany two clamping limbs, the medial surface of each clamping limb is relative with the medial surface of another clamping limb, one of clamping limb it is interior
The sample introduction end of the micro-fluidic chip is close in side, and the medial surface of another clamping limb is close to the ultrasonic wave damper, the elastic force
Folder with its gripping strength by the sample introduction end of the micro-fluidic chip and the ultrasonic wave damper it is bonded to each other clip together, the ultrasonic wave
The strong consumption to ultrasonic energy that damper is brought with its material, is further supported in the micro-fluidic chip terminal
The rapid decrement of ultrasonic intensity is realized within to the limited short distance between the sample introduction end, and is thereby entered described in further expansion
Difference between its interfacial tension of sample end and the terminal its interfacial tension.
The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and cholera specific antibody solution uniformly, uses point sample instrument
Point sample is coated on specified structure position, and forms its drying and forming-film.Cholera specific antibody in the gold size sensitive membrane is equal
The cholera antibody marked for horseradish peroxidase or glucose oxidase, the gold size sensitive membrane has been included as fixing above-mentioned each
Cholera specific antibody and introduce complementary medium therein, the complementary medium such as chitosan, cellulose acetate, gelatin
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 four-way micro-fluidic chip, using four-way electrochemical analytical instrument respectively to four kinds of cholera
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 cholera antigen molecules are by each passage
The cholera specific antibody capture for the corresponding horseradish peroxidase-labeled that gold size sensitive membrane is embedded on electrode surface.
2nd, the cholera antigen formation immune complex in the cholera specific antibody and blood serum sample of horseradish peroxidase-labeled.
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 cholera 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.
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.
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.
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, 1,2,10 be the different liquid pool of three installation positions respectively, and 3 be manifold shape turnout, 4,7,11,14
It is that installation position is different but four laterals parallel with one another for forming UNICOM's structure in parallel respectively, 5 be to be installed in lateral 4
Specific antibody material in the interior sensitive membrane structure of its top layer gold size is the working electrode of cholera TP0821 antibody, and 6 be installing
The specific antibody material in the sensitive membrane structure of its top layer gold size in lateral 7 is electric for the work of cholera TP0319 antibody
Pole, 12 be that specific antibody material in the sensitive membrane structure of its top layer gold size being installed in lateral 11 is cholera
The working electrode of TP0624 antibody, 13 be the specificity in the sensitive membrane structure of its top layer gold size being installed in lateral 14
Antibody materials are the working electrode of cholera O139 mycoprotein antibody, and 8 be that, to electrode, 9 be reference electrode, and 15 be poly- diformazan
The substrate of radical siloxane material, 16 be cover plate, and 17 be higher-order of oscillation electric signal transmission cable, and 18 be miniature ultrasonic transducer units,
19 be the sample introduction end of the micro-fluidic chip, and 20 be the terminal of the micro-fluidic chip；Arrow sign in legend
The 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 15 and cover plate 16 of installing bonded to each other together, the substrate 15 and cover plate 16
It is plate object or tablet, that face towards the cover plate 16 of the substrate 15 is contained via mould pressing process or etching technics shape
Into channel structure, the substrate 15 also containing be connected with the channel structure and pierce the substrate via mould pressing process, etch
Technique or the window structure of simple drilling technology formation, substrate 15 bonded to each other being installed together and the common structure of cover plate 16
Built up the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the liquid pool be liquid pool 1, liquid pool 2,
Liquid pool 10, the locations of structures of the pipeline is located at the substrate 15 and the cover plate 16 interface zone bonded to each other, the window one
Side is blocked by the cover plate 16 and opposite side is opened, and the locations of structures of the window is exactly the liquid pool 1, liquid pool 2, liquid pool 10
Locations of structures, the quantity of the liquid pool is three, and two liquid pools therein are that liquid pool 1 and its locations of structures of liquid pool 2 are micro- positioned at this
The sample introduction end 19 of fluidic chip, a remaining liquid pool is that its locations of structures of liquid pool 10 is surveyed positioned at the actual sample introduction of the micro-fluidic chip
The terminal 20 that liquid flows in its chip during examination, the terminal 20 is located remotely from each other with the sample introduction end 19, one end of the pipeline via
Be similarly positioned in the manifold shape turnout 3 of the interface zone bonded to each other respectively with positioned at the liquid pool 1 at sample introduction end 19 and the liquid pool
2 UNICOMs, the other end of the pipeline and a remaining liquid pool for the terminal 20 positioned at the micro-fluidic chip are liquid pool 10
UNICOM, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode 8 and reference electrode 9,
The working electrode is quick by conductive electrode and the gold size for having embedded cholera specific antibody being attached on the conductive electrode
Feel film to constitute, the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of four lateral parallel connections, institute
The quantity for stating working electrode is four, and the installation position of four working electrodes is located in four laterals respectively, and this four
Individual working electrode is working electrode 5, working electrode 6, working electrode 12, working electrode 13 respectively, and, this four work
Specific antibody in the sensitive membrane structure of its top layer gold size of electrode is that the four kinds of cholera that can be specifically bound to cholera antigen resist respectively
Body material, four kinds of antibody materials are cholera TP0821 antibody and cholera TP0319 antibody and cholera TP0624 respectively
Antibody and cholera O139 mycoprotein antibody, for specifically deploying, 5 be its top layer gold being installed in lateral 4
Specific antibody material in glue sensitivity membrane structure is the working electrode of cholera TP0821 antibody, and 6 be to be installed in lateral 7
Specific antibody material in the interior sensitive membrane structure of its top layer gold size is the working electrode of cholera TP0319 antibody, and 12 be dress
Specific antibody material in the sensitive membrane structure of its top layer gold size being located in lateral 11 is the work of cholera TP0624 antibody
Make electrode, 13 be that specific antibody material in the sensitive membrane structure of its top layer gold size being installed in lateral 14 is cholera
The working electrode of O139 mycoprotein antibody, the working electrode 5, working electrode 6, working electrode 12, working electrode 13
Its material be gold material or thermal decomposition conducting polymer material, the working electrode 5, working electrode 6, working electrode 12,
Sheet or thread is presented in working electrode 13 its pattern, and emphasis is, its material of the substrate 15 is dimethyl silicone polymer material, should
Its surface of substrate 15 is the surface of primary form, the surface of the primary form its be intended to refer to not pass through any surface chemistry
The surface of the primary form of the material of modification or any surface chemical modification, the structure of the micro fluidic device also includes miniature ultrasonic
Wave transducer 18, and, higher-order of oscillation electric signal transmission cable 17, one end of the higher-order of oscillation electric signal transmission cable 17
Linked together with the miniature ultrasonic transducer units 18, the miniature ultrasonic transducer units 18 are installed in the micro-fluidic core with attaching
The position of the cover plate 16 of piece or the neighbouring terminal 20 of substrate 15；Its major function of the miniature ultrasonic transducer units 18 is
In the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it reduce sample solution and the pipeline inwall it
Between interfacial tension, can be compatible, also, utilize the sample introduction end 19 and the terminal 20 and the miniature ultrasonic
Difference in the distance between the installation position of wave transducer 18 difference and its ultrasonic intensity experienced, induced synthesis institute
State the difference between its interfacial tension of sample introduction end 19 and the terminal 20 its interfacial tension, the micro-fluidic chip two ends be into
Interfacial tension difference between sample end 19 and terminal 20 can be sample introduction end 19 and terminal 20 at the two ends of the micro-fluidic chip
Between form pressure gap, the pressure gap can drive sample solution to be flowed to the direction of terminal 20；The miniature ultrasonic is changed
Can device 18 its function also include with its ultrasonic wave launched check large biological molecule contained in sample its in the pipeline
Absorption on surface, and then check swallow up work of its body phase of the substrate 15 of the dimethyl silicone polymer material to the large biological molecule
With；The substrate 15 of the dimethyl silicone polymer material its function include with cover plate 16 and working electrode 5, working electrode 6,
Working electrode 12, working electrode 13 and the micro-fluidic chip is together built to electrode 8 and reference electrode 9, it is soft simultaneously to have 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 19 of the micro-fluidic chip, the medial surface of another clamping limb is close to the ultrasonic wave damper, the elastic clip
With its gripping strength by the sample introduction end 19 of the micro-fluidic chip and the ultrasonic wave damper it is bonded to each other clip together, the ultrasound
The strong consumption to ultrasonic energy that ripple damper is brought with its material, is further supported at the micro-fluidic chip end
End 20 is and thereby further to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 19
Expand the difference between described its interfacial tension of sample introduction end 19 and the terminal 20 its interfacial tension.This is depicted without in legend
Also the elastic clip is depicted without in ultrasonic wave damper, legend.
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 18 and higher-order of oscillation electric signal transmission cable 17 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 18 are commercially available；It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal transmission cable 17 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.
Capillary on usual expression and significance refers to hydrophilic capillary glass tube；Capillary channel involved by this case is hydrophobic
Capillary form pipeline.
Claims (10)
1. cheap micro fluidic device is used in the cholera diagnosis for relying on interfacial characteristics to carry out liquid stream driving, 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
It is plate object or tablet with cover plate, that face towards the cover plate of the substrate is contained via mould pressing process or etching technics shape
Into channel structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics
Or the window structure of simple drilling technology formation, substrate bonded to each other being installed together has been built into jointly with the cover plate to be contained
The micro-fluidic chip of pipeline configuration and the liquid pool structure being attached thereto, the locations of structures of the pipeline is located at the substrate and the cover plate phase
The interface zone mutually fitted, 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 described
The locations of structures of liquid pool, the quantity of the liquid pool is three, and its locations of structures of two liquid pools therein is located at the micro-fluidic chip
Sample introduction end, its locations of structures of a remaining liquid pool is located at liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested
Terminal, the terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is via the discrimination for being similarly positioned in the interface zone bonded to each other
Tubulose turnout respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline with it is described positioned at the micro-fluidic chip
A remaining liquid pool UNICOM for terminal, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and
To electrode and reference electrode, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded cholera
The gold size sensitive membrane of specific antibody is constituted, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by four points
Branch pipe(tube) parallel connection is constituted, and the quantity of the working electrode is four, and the installation position of four working electrodes is located at described four respectively
In bar lateral, and, the specific antibody in the sensitive membrane structure of its top layer gold size of four working electrodes is to cholera respectively
Four kinds of cholera antibody materials that antigen can be specifically bound, four kinds of antibody materials are cholera TP0821 antibody and cholera respectively
TP0319 antibody and cholera TP0624 antibody and cholera O139 mycoprotein antibody, its material of the working electrode is
Sheet or thread is presented in gold material or thermal decomposition conducting polymer material, its pattern of the working electrode, it is characterised in that should
Its material of substrate 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 micro fluidic device also includes miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, the higher-order of oscillation
One end of electric signal transmission cable links together with the miniature ultrasonic transducer units, and the miniature ultrasonic transducer units attach ground installing
The micro-fluidic chip cover plate or substrate the neighbouring terminal position；Its major function of the miniature ultrasonic transducer units be
During the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it is reduced between sample solution and the inwall of the pipeline
Interfacial tension, can be compatible, also, filled using the sample introduction end and the terminal with the miniature ultrasonic transducer units
If the difference on the distance between position difference and its ultrasonic intensity experienced, its interface of sample introduction end described in induced synthesis
Interfacial tension difference between difference between tension force and the terminal its interfacial tension, the micro-fluidic chip two ends can be micro- at this
Pressure gap is formed between the two ends of fluidic chip, the pressure gap can drive sample solution to the end flow；This is miniature
Ultrasonic transducer its function also include with its ultrasonic wave launched check large biological molecule contained in sample its described
Absorption on inner surface of pipeline, and then check the substrate of the dimethyl silicone polymer material its body phase the large biological molecule is swallowed up
Effect；Its function of the substrate of the dimethyl silicone polymer material is included with cover plate and working electrode and to electrode and reference electrode one
It is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and also include with it to super with building the micro-fluidic chip
The property that sound wave absorbs strongly, is absorbed strongly to ultrasonic wave, and thereby micro-fluidic chip terminal to the sample introduction end it
Between limited short distance within realize the rapid decrement of ultrasonic intensity；And, ultrasonic wave damper, the ultrasonic wave damper
Its profile is in block, tabular or bar-shaped；Its material of the ultrasonic wave damper is microcellular rubber, sponge rubber or microporous polyurethane bullet
Property body；And, elastic clip, the elastic force accompanies two clamping limbs, the medial surface of each clamping limb and the inner side of another clamping limb
Face is relative, and the medial surface of one of clamping limb is close to the sample introduction end of the micro-fluidic chip, and the medial surface of another clamping limb is tight
Close to the ultrasonic wave damper, the elastic clip is with its gripping strength by the sample introduction end of the micro-fluidic chip and the ultrasonic wave damper phase
Mutually snugly clip together, the strong consumption to ultrasonic energy that the ultrasonic wave damper is brought with its material enters one
Step is supported to realize the quick of ultrasonic intensity within micro-fluidic chip terminal to the limited short distance between the sample introduction end
Successively decrease, and thereby further expand the difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension.
2. cheap micro fluidic device is used in the cholera for relying on interfacial characteristics to carry out liquid stream driving diagnosis according to claim 1, its
It is characterised by, the pipeline and the lateral and the manifold shape turnout are capillary channel.
3. cheap micro fluidic device is used in the cholera for relying on interfacial characteristics to carry out liquid stream driving diagnosis according to claim 1, its
Be characterised by, the thermal decomposition conducting polymer be by polyimides or polyacrylonitrile be heat-treated through anoxybiotic after the electric conductivity material that is formed
Material.
4. cheap micro fluidic device is used in the cholera for relying on interfacial characteristics to carry out liquid stream driving diagnosis according to claim 1, its
Be characterised by, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, work electricity
The length of pole is between 1 micron to 15000 microns.
5. cheap micro fluidic device is used in the cholera for relying on interfacial characteristics to carry out liquid stream driving diagnosis according to claim 1, its
It is characterised by, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. cheap micro fluidic device is used in the cholera for relying on interfacial characteristics to carry out liquid stream driving diagnosis according to claim 1, its
It is characterised by, its material of the cover plate in structure is dimethyl silicone polymer material.
7. cheap micro fluidic device is used in the cholera for relying on interfacial characteristics to carry out liquid stream driving diagnosis according to claim 1, its
Be characterised by, 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
Under a liquid pool between air line distance between 3 centimetres and 7 centimetres；The cover plate and its thickness of substrate in structure is equal
Between 1.0 millimeters and 5.0 millimeters.
8. cheap micro fluidic device is used in the cholera for relying on interfacial characteristics to carry out liquid stream driving diagnosis according to claim 1, its
It is characterised by, the microcellular rubber is micropore silicon rubber or micropore fluorubber.
9. cheap micro fluidic device is used in the cholera for relying on interfacial characteristics to carry out liquid stream driving diagnosis according to claim 1, its
It is characterised by, the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission electricity
Its other end of cable is connected with the higher-order of oscillation electric signal generator.
10. cheap micro fluidic device is used in the cholera for relying on interfacial characteristics to carry out liquid stream driving diagnosis according to claim 1, its
It is characterised by, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 2 milliwatts and 2000 milliwatts, and this is micro-
The frequency of its ultrasonic wave operationally launched of type ultrasonic transducer is between 100KHz and 12MHz.
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| CN201610065951.6A CN106990240A (en) | 2016-01-20 | 2016-01-20 | Cheap micro fluidic device is used in the cholera diagnosis for relying on interfacial characteristics to carry out liquid stream driving |
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| CN201610065951.6A CN106990240A (en) | 2016-01-20 | 2016-01-20 | Cheap micro fluidic device is used in the cholera diagnosis for relying on interfacial characteristics to carry out liquid stream driving |
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