CN107649218A - The cholera diagnosis micro fluidic device of quick removal is capable of in sample liquid driving with component - Google Patents
The cholera diagnosis micro fluidic device of quick removal is capable of in sample liquid driving with component Download PDFInfo
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- CN107649218A CN107649218A CN201610627489.4A CN201610627489A CN107649218A CN 107649218 A CN107649218 A CN 107649218A CN 201610627489 A CN201610627489 A CN 201610627489A CN 107649218 A CN107649218 A CN 107649218A
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- B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
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Abstract
The present invention relates to the cholera diagnosis micro fluidic device that a kind of sample liquid driving component is capable of quick removal, belong to analysis testing field.Serial problem be present if for making the substrate of cholera diagnosis micro-fluidic chip in 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, its effect are 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 the chain ring type magnetic holding device for being equiped with miniature ultrasonic transducer units socket is positioned at the sample liquid stream terminal of the micro-fluidic chip its neighbor positions, interfacial tension is reduced with ultrasonic wave, strong absorbability using PDMS to ultrasonic wave simultaneously, reach ultrasonic intensity rapid decrement in short distance, so as to form interfacial tension difference at the both ends of the chip, sample liquid stream is thereby facilitated to be flowed along originally hydrophobic capillary channel to the terminal direction.
Description
Technical field
The present invention relates to the cholera diagnosis micro fluidic device that a kind of sample liquid driving component is capable of quick removal, belong to
Analyze testing field.
Background technology
The micro-fluidic cholera diagnostic techniques background of associated multi-channel, may refer to the patents of invention such as CN 200910150930.4
Application case.
Only for the microflow control technique overall general picture of itself, famous micro-fluidic expert Mr. Lin Ping Cheng may refer to not
The monograph " diagram Microfluid based Lab on a chip " gone out before long, the monograph is published via Science Press, and the monograph is for miniflow
Past of control technology, now, and, vision of the future etc. etc., suffer from detail, be deep into long opinion of detail
State.
So, the Important Problems of this case that to have a talk below concern.
The basic framework of micro-fluidic chip, including be etched with the substrate of small fluid course and fit together therewith
Cover plate, the small fluid course on the substrate, before upper cover plate is assembled, it is apparent on see to be exactly some micro-channels, to wait until
After covering cover plate thereon, just really closure forms the small fluid course, the conduit inner surface of the micro-channel together with
The part cover plate that surround the micro-channel forms described small fluid course together；So, it is clear that after assembling completes
The small fluid course, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, should
The state or property of micro-channel inner surface substantially determine the integrality or property of the small fluid course；Therefore say, this
The inner surface state or inner surface property of micro-channel of the individual structure on substrate are key factors；In principle, it is any can
The material of its solid forms is kept or kept substantially, can be used to make substrate and cover plate, such as, it can act as substrate and lid
The material of piece can be monocrystalline silicon piece, quartz plate, sheet glass, high polymer for example dimethyl silicone polymer, polymethyl methacrylate,
Makrolon etc.；Certainly, the selection of substrate and the selection of cover plate be able to can also be differed with identical；From material consumption, make
From the point of view of difficulty and application popularization prospect etc. etc., not small difference, the especially choosing of that substrate between these materials be present
Material, have a great influence.
In various substrate making materials, dimethyl silicone polymer, i.e. PDMS, comparatively very easily shaping, at this
It is extremely simple that micro-channel is made on the substrate of sample, and the lower cost for material, base is made with the polydimethyl siloxane material
Piece, micro-channel, and the cover plate phase made with the cheap material such as glass or polypropylene or other plastic sheets are being suppressed or etched thereon
Coordinate, be a kind of more satisfactory selection seemingly；Certainly, patch material can also select to use cheap dimethyl silicone polymer
Material：So, this substrate selection is the scheme of polydimethyl siloxane material, and material is extremely cheap, and making is extremely simple, seems
It should be extremely easy to popularize, promote.
But thing is really not so simple.
First, this polydimethyl siloxane material, that is, the material that alphabetical PDMS is referred to of abridging, itself are a kind of strong
Strong hydrophobic material, micro-channel is built on this material, if without being operated for the modified of the micro-channel surface, that
, after overall assembling is completed, that is, after covering cover plate, because the micro-channel its inner surface in structure occupies most liquid
The inner surface of circulation road, then, its strong hydrophobic property of the PDMS micro-channels inner surface, is deciding factor, it can cause
Similar to the aqueous solution the fine liquid stream of polar liquid by becoming very difficult, its flow resistance is big, or even in general is micro-
Pump is all difficult to promote, certainly, if cover plate also selects to use the PDMS material, then, problem is substantially identical, similar；
Therefore, among prior art, modification is modified particular for the micro-channel inner surface on the PDMS material, is necessary behaviour
Make；So, this is pretty troublesome for the modified operation of PDMS micro-channel inner surfacesThat falls nor this problem, is formed tight
Weight technology puzzlement, be another problem：PDMS polymer molecules inside its body phase of this PDMS material substrate have automatic
The characteristic diffuse to the surface, migrated, the spy that this substrate body phase inside PDMS polymer molecules are diffused to the surface, migrated automatically
Property, the state after modification by its inner surface of that micro-channel of surface modifying and decorating will be caused can not to maintain long enough
Time, the holding time for micro-channel its inner surface state after that is surface-modified be substantially only sufficient to complete laboratory internal
The time of test experiments needs；In other words, by surface modification or the PDMS micro-channel inner surfaces of surface modification, it is modified
The surface state that is formed can not be lasting afterwards or after saying modification, but soon automatically tends to or say and become surface modification again
Surface state before, the strong hydrophobic surface state of that script is returned in the shorter time, then, just think, this
The micro-fluidic chip of sample can largely make, mass storage, be widely popularized, and answer is it is obvious that is, impossible.This
Micro-channel on PDMS material, if not doing surface modification, similar to the aqueous solution the fine liquid stream of polar solvent can not pump it is logical
Cross, chip also cannot just use；And if having done surface modification, its state after modifying can not be persistently kept again, or together
Sample can not popularization and application.
So, how to accomplish that substrate can either be made using cheap PDMS material, and the microflute can be released
Road inner surface decorating state can not persistently, chip can not largely make, largely lay in and then be widely popularized and such a make ability
The puzzlement that the numerous professionals in domain are entangled with for a long time, the highly difficult problem that exactly one its obvious technology barrier can not despise.
Be present many year in the highly difficult problem, so far, not yet properly settled.
Second, the PDMS material of non-surface modification, it is stated that, its surface is strongly hydrophobic above, this strong hydrophobic
Material surface and also have another problem, that is, this strong hydrophobic PDMS surfaces can adsorb large biological molecule, and
And these adsorbed large biological molecules can also further depression further on PDMS surfaces, gradually fall into it is gradually deep, until
It is heavy to be trapped within the body phase of PDMS substrates, in fact, this process, partly it is also due to PDMS material body phase interior polymer
Molecule, which has, to be diffused to the surface, caused by travel motion；Such case, it can also be explained from another angle, i.e. continue not
Disconnectedly from inside PDMS body phases to those polymer molecules of its diffusion into the surface, migration, its result moved, be little by little by that
It has been involved in a bit by the large biological molecule of adsorption within the body phase of PDMS substrates, briefly, these adsorbed biologies
Macromolecular is exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up the phenomenon of large biological molecule, its institute
Caused by influence, necessarily cause the severe deviations of all kinds of test data of experiment for being related to large biological molecule.
As described above, the problem of PDMS substrates, is, its not only adsorption large biological molecule, and swallow up biological big point
Son, so, as the large biological molecule of experiment test object, its disappearance will not stop because surface saturation is adsorbed, and
It is, it is constantly adsorbed, also constantly swallowed up.
On PDMS substrates, its body phase is constantly swallowed up and tests showing for associated biomolecule macromolecular in related experiment test process
As, it is to say that another kind, which is explained, substantial amounts of Minute pores in PDMS body phases be present, associated biomolecule macromolecular by after adsorption,
Depression enters these Minute pores, and then is swallowed up；However, inventor thinks, those can allow the sky of miniature scale
Qi leel squeezes into the Minute pores therebetween, not equal to saying that they also can directly allow the large biological molecule of relative large scale to enter
Enter, both difference on yardstick are huge, must not make sweeping generalizations.Explanation is bypassed, in any case, as dependence test analysis object
Large biological molecule is adsorbed by PDMS substrate micro-channels inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is person in charge of reception at ceremonies
Phenomenon existing for sight.
, can be from containment PDMS surfaces pair in order to prevent swallow up effect of this PDMS substrate bodies relative to large biological molecule
The absorption of large biological molecule addresses, and method is chemically modified modification aiming at the PDMS material surface, for
For PDMS is the situation of substrate material, modification exactly is chemically modified to the surface of described micro-channel part, by changing
The micro-channel inner surface of modification is learned, its absorption to large biological molecule can be contained, and then avoid large biological molecule
Swallowed up by PDMS substrate body phases；But or that old problem, that is, the chemical modification on PDMS material surface is modified
Surface state afterwards can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface, move automatically
The process of shifting, it soon can become that micro-channel inner surface state being modified by surface chemical modification again script strong and dredge
Water and the state of strong adsorption large biological molecule, in other words, no matter how professionals in the field turn from side to side, the PDMS bases
Its micro-channel inner surface of piece is always rapidly to strong hydrophobic surface state evolution.
So, how can either obtain that PDMS material price is extremely cheap, substrate makes extremely easy benefit, and can is enough
Reach and contain the absorption process of the PDMS substrate micro-channel inner surfaces to large biological molecule for a long time, and then prevent PDMS substrate body phases
The effect of swallowing up to large biological molecule so that related chip manufactured goods be able to maintain that one it is prolonged enough, reasonably guarantee the quality
Phase, it is exactly a very intractable problem.The problem equally makes this area numerous as another problem addressed above
Professional is entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise.
Also be present many year in the problem, so far, also not yet properly settled.
The content of the invention
The technical problem to be solved by the invention is to provide a package solution, solves totally above
Two problems addressed, also, the solution is applied to cholera diagnosis multichannel micro-fluidic chip field, formed a kind of
Multichannel micro-fluidic device is used in new cholera diagnosis.
The present invention solves the technical problem by following scheme, and the device that the program provides is that a kind of sample liquid driving is used
Component is capable of the cholera diagnosis micro fluidic device of quick removal, and the structure of the micro fluidic device includes multichannel micro-fluidic core
Piece, the structure of the micro-fluidic chip include being bonded to each other the substrate and cover plate of installing together, and the substrate and cover plate are plate
The conduit knot via mould pressing process or etching technics formation is contained in shape thing or tablet, that face towards the cover plate of the substrate
Structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or simply beat
The window structure that hole technique is formed, it is bonded to each other the substrate being installed together and has been built into jointly with the cover plate and contain pipeline knot
The micro-fluidic chip of structure and the liquid pool structure being attached thereto, the locations of structures of the pipeline are located at the substrate and mutually pasted with the cover plate
The interface zone of conjunction, its side of the window is blocked by the cover plate and opposite side opens, and the locations of structures of the window is exactly the liquid
The locations of structures in pond, 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 are 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 being similarly positioned in the interface zone being bonded to each other
Manifold shape turnout respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline and be located at the micro-fluidic chip
The terminal a remaining liquid pool UNICOM, and, be sequentially respectively installed in the work on diverse location in the pipeline
Electrode and to electrode and reference electrode, the working electrode is by conductive electrode and is attached on the conductive electrode
The gold size sensitive membrane for having embedded cholera specific antigen is formed, and the construction of the pipeline is in parallel construction, and described is in parallel construction
Pipeline is made up of four lateral parallel connections, and the quantity of the working electrode is four, the installation position of four working electrodes
Respectively in four laterals, and, the specificity in its top layer gold size sensitivity membrane structure of four working electrodes
Antigen is the four kinds of cholera antigenic substances that can be specifically bound to cholera antibody respectively, and four kinds of antigenic substances are cholera respectively
TP0821 antigens and cholera TP0319 antigens and cholera TP0624 antigens and cholera O139 antigens, the working electrode its
Material is that sheet or thread is presented in gold material or thermal decomposition conducting polymer material, the working electrode its pattern, and emphasis is,
Its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, the table of the primary form
Face its be intended to refer to the not no primary form of the material by any surface chemical modification or any surface chemical modification
Surface, the structure of the device also include chain ring type magnetic holding device, and six links, institute are shared in its structure of the chain ring type magnetic holding device
Link is stated in strip, shaft-like or bar-shaped, each adjacent link is hinged to form chain link, and its appearance profile of the chain link is hexagonal
Cyclic structure, its locations of structures of each drift angle of the hexagonal annular structure is articulated structure position, the hexagonal annular knot
Two therein of structure is magnetic conductivity material in the link of opposite side position its material, four rings of remainder of the hexagonal annular structure
It is non-magnetic material to save its material, and the non magnetic material refers to the material not responded strongly to externally-applied magnetic field, and this is led
Magnet exciting coil is wound with a link among two links of magnetic material, the link for being wound with magnet exciting coil is encouraged at it
The pole shoe of a magnetic conductivity material is respectively equiped with the both sides neighbor positions of magnetic coil, shares two pole shoes, two poles
Boots are directed to the link of another magnetic conductivity material, and fixation is attached on its surface of the link of another magnetic conductivity material and is equiped with
Miniature ultrasonic transducer units, the chain ring type magnetic holding device socket of electromagnetism adhesive strength is relied on to be positioned at its institute of the micro-fluidic chip
State the close position of terminal, 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 chain ring type magnetic holding device provides a function of facilitating the device to disassemble；
Its major function of the miniature ultrasonic transducer units is the ultrasonic wave launched using it in the test of micro-fluidic chip actual sample introduction
, can be compatible to reduce the interfacial tension between sample solution and the inwall of the pipeline, also, utilize the sample introduction end
And the distance between the terminal and the miniature ultrasonic transducer units installation position difference and its ultrasonic wave experienced
Difference between difference in intensity, its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension, this is micro-
Interfacial tension difference between the fluidic chip both ends can form pressure gap between the both ends of the micro-fluidic chip, the pressure
Power difference can drive sample solution to the end flow；Its function of the miniature ultrasonic transducer units also includes what is launched with it
Ultrasonic wave checks in sample contained its absorption on the inner surface of pipeline of large biological molecule, and then checks the poly- diformazan
Swallow up effect of its body phase of the substrate of radical siloxane material to the large biological molecule；The substrate of the dimethyl silicone polymer material
Its function 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, ultrasonic wave is entered
Row is strong to be absorbed, and ultrasound is thereby realized within micro-fluidic chip terminal to the limited short distance between the sample introduction end
The rapid decrement of intensity of wave, its locations of structures are located at the end of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested
A remaining liquid pool at end is also referred to as terminal liquid pool, and some high hydroscopic resin particles, the end are filled with the terminal liquid pool
Liquid pool its opening end in end is covered by breathable microporous film.
The word of magnet exciting coil one art-recognized meanings of itself are known.
The word of magnetic conductivity material one art-recognized meanings of itself are known；The material for belonging to magnetic conductivity material is for example pure
Iron, silicon steel, soft magnetic ferrite etc..
Non magnetic material described in this case refers to the material not responded strongly to externally-applied magnetic field, belongs to the non magnetic material
The material of matter such as metallic copper, metallic zinc, ormolu, metallic aluminium, almag etc..
The be hinged word art-recognized meanings of itself field in Machine Design is known.
The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and cholera specific antigen solution uniformly, is used a little
Sample instrument point sample is coated on specified structure position, and forms its drying and forming-film.Cholera specificity in the gold size sensitive membrane
Antigen is the cholera antigen of horseradish peroxidase or glucose oxidase mark, and the gold size sensitive membrane has been included as solid
Determine above-mentioned each cholera specific antigen and introduce complementary medium therein, the complementary medium such as chitosan, acetic acid are fine
Dimension is plain, gelatin is therein a kind of or their mixture.
The pipeline and the lateral and the manifold shape turnout in the microfluidic chip structure, in it
Footpath size may each be arbitrarily selected size, still, for as far as possible less with prepare liquid sample and reduction reagent loss etc.
Consideration, the pipeline and the lateral and the manifold shape turnout preferably select capillary level passage, institute
The passage for stating capillary level implies that its internal diameter passage suitable with the internal diameter of the capillary on ordinary meaning.The capillary is in it
The shape of cross section of portion's passage can be arbitrary shape, and the shape of cross section is for example circular, oval, square, rectangle, bar
Shape, naturally it is also possible to it is the linear of bending arbitrarily be present, also, the interior shape of the capillary is with the extension of pipeline,
The shape of cross section of different parts can also allow to be different shapes.Only for the word of capillary one, its art-recognized meanings is public
Know.
What is be related in structure is the electrode of microsize to electrode and reference electrode, and its electrode shape, which may each be, appoints
The selected shape of meaning, the arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..It is described
Art-recognized meanings to electrode 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 capsule for transitional liquid storage
Shape constructs, and its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, and the cavity shape is for example round
Cylindrical cavity shape, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..The size of the liquid pool can be any
Selected size, still, in order to as far as possible less with prepare liquid sample and reduce reagent loss, the liquid pool be preferably capable of with
The liquid pool of the microminiature of capillary matching.
Only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field,
It is known.
Various sizes, variously-shaped ultrasonic transducer are commercially available；Its size of commercially available miniature ultrasonic transducer units
It may diminish to the magnitude only calculated with millimeter.
Only with regard to miniature ultrasonic transducer units its technique for fixing on general industry application solid body surface its
It is known general technology for the professional in ultrasonic technology field for body.This case is not to this expansion superfluous words.
Only with regard to naked PDMS substrates itself micro-channel molding or lithographic technique for, be open-and-shut known skill
Art；Similarly, the technology of hole-opening is even more known simple technique on naked PDMS substrates.This case is not also superfluous to this expansion
Speech.
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 passes
Its other end of transmission 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, come for the professional in ultrasonic technology field
Say, be simple and known；The higher-order of oscillation electric signal generator can customize to ultrasonic instrument specialized factory.
The preferred scope of its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 5 milliwatts and 9000 milliwatts
Between；The preferred scope of the frequency of its ultrasonic wave operationally launched of the miniature ultrasonic transducer units be between 100KHz with
Between 12MHz.
Only for the word of high hydroscopic resin one art-recognized meanings of itself, come for the professional of chemical field
Say, be known.
The high hydroscopic resin is commercially available.
Only for the word of breathable microporous film one art-recognized meanings of itself, for the professional of technical field of membrane,
It is known.
The breathable microporous film is commercially available.
This case device can further include some annexes certainly, and the annex is such as multiple tracks electrochemical workstation
Deng the art-recognized meanings of the multiple tracks electrochemical workstation are known.The each work being related in this case microfluidic chip structure
Electrode and to electrode and reference electrode etc., special it can get lines crossed and the multiple tracks electrochemical workstation via corresponding respectively
The corresponding interface coupled.It is described that special to get lines crossed be for by each phase of each electrode and the multiple tracks electrochemical workstation
Answer the private cable that interface is coupled to each other.The micro-fluidic chip in this case device, its structure can also include micro-valve,
The quantity of the micro-valve is unlimited, and according to being actually needed, the micro-valve can be installed in any need in the microfluidic chip structure
Position to be mounted；The word of micro-valve one is for the professional of micro fluidic chip technical field, the art-recognized meanings of itself
It is known；The micro-valve itself manufacturing technology and the use of technology is also known；The component that the micro-valve is not required.
The diameter of the working electrode can allow to be that any setting is easily installed the suitable diameter used, still,
It is recommending or say preferable its scope of the diameter between 0.1 micron to 2000 microns；The length of the working electrode can
To allow to be that any setting is easily installed the length used, it is however recommended to or to say the preferable length its scope be 1
Micron is between 15000 microns.
It is installed in by spraying or point sample instrument point sample or the coating of other appropriate process described in the working electrode surface layer
Gold size sensitive membrane, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness,
It is however recommended to thickness preferable thickness is between 10 nanometers and 200 nanometers in other words.
The cover plate in chip structure, its material can allow to be any electrical insulating property material, such as：Polypropylene,
Glass, polymethyl methacrylate, dimethyl silicone polymer, etc., in order to make smaller size of micro-fluidic chip, for example do
Into the micro-fluidic chip of only 2.0 centimetres to 3.0 centimetres of super-small of length, and realized in the extremely short distance to ultrasonic wave
Extremely fast decay, can preferably dimethyl silicone polymer be used as cover plate.Certainly, selected on large-sized micro-fluidic chip
Using dimethyl silicone polymer it is used as the cover plate, and this case technical scheme is allowed.
Positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal should
Air line distance between a remaining liquid pool can be arbitrarily selected suitable distance, still, the distance as needed
Preferred value is between 3 centimetres and 7 centimetres.
Described its thickness of cover plate and substrate can allow be any setting the thickness for being easy to assembling, the thickness of recommendation or say
Preferable thickness is between 1.0 millimeters and 5.0 millimeters.Less thickness is advantageous to save material.
The application method of this case micro-fluidic chip：
Itd is proposed first based on this case and the first public new liquid stream driving principle, its application of this case micro-fluidic chip are transported
Among work, the new liquid stream driving method is determined completely without involving any additional Micropump.
The interfacial tension difference that this case is formed between micro-fluidic chip both ends caused by the ultrasonic wave,
Driving liquid stream flows in the capillary channel of the four-way micro-fluidic chip, right respectively using four-way electrochemical analytical instrument
Four kinds of cholera antibody are detected.
Corresponding four kinds of cholera antibody is detected with four kinds of cholera antigens, with detecting corresponding four with four kinds of cholera antibody
Kind cholera antigen, similarly, can cholera diagnosis；The principle of its foundation is, necessarily antigen, antibody in cholera patient
And deposit, and mutual Reversible binding forms reversible conjugate, therefore, antibody and thereby cholera diagnosis is detected with antigen, with
Antibody goes to detect antigen and cholera diagnosis, can reach diagnostic purpose.Certainly, its corresponding electrode sensitive of different means is repaiied
Adorn layer technically and differ.
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 antibody molecules are by each logical
The cholera specific antigen for the corresponding horseradish peroxidase-labeled that gold size sensitive membrane embeds captures on electrode surface in road.
2nd, the cholera specific antigen of horseradish peroxidase-labeled is formed immune multiple with the cholera antibody in blood serum sample
Compound.
3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, it is above-mentioned using amperometric detection
Curent change caused by reaction, it is derived from the species and content of various analytes.
4th, result is subjected to comprehensive analysis, comprehensive diagnos is carried out to cholera antibody.
It is an advantage of the invention that its close position relies on electromagnetism adhesive strength set in the terminal of the micro-fluidic chip
The described chain ring type magnetic holding device of positioning is connect, is installed with institute's attaching in the chain ring type magnetic holding device one magnetic conductivity link micro-
Type ultrasonic transducer, the low-power launched using it, the ultrasonic wave of high-frequency band so that without surface chemical modification or
It is compatible between strong hydrophobic its tube wall of micro-fluidic chip internal pipeline and the test object aqueous solution of surface chemical modification
Property be significantly increased, this is sample liquid stream by providing a realistic possibility；Meanwhile utilize dimethyl silicone polymer substrate
Its strong absorbability to ultrasonic wave, in shorter distance, it is, from the terminal to the sample introduction end
In the very short distance of only several centimeters yardsticks, reach the rapid decrement of ultrasonic intensity, thereby described in the micro-fluidic chip
The difference of the interfacial tension is caused at both ends, and then, using the interfacial tension between the both ends difference its formed this two
Pressure gap between end, driving sample liquid stream is in the strong hydrophobic capillary channel of such a script to the terminal side
To flowing.By this case liquid stream drive scheme, entirely without must be to the substrate and its internal pipeline of the dimethyl silicone polymer material
Any surface chemical modification or chemical modification are carried out, has altogether dispensed with the trouble journey of the surface chemical modification or chemical modification
Sequence；And the equipment of traditional Micropump etc is altogether dispensed with；On the other hand, the low-power, the ultrasound of high-frequency band
Ripple, additionally it is possible to contain large biological molecule in sample in literalness naked its inner surface of pipeline of dimethyl silicone polymer substrate
On absorption, and then contain the swallow up effect of its body phase of dimethyl silicone polymer substrate to the large biological molecule；It is described anti-
Former, antibody and the Reversible binding thing of antigen and antibody are all the type for belonging to described large biological molecule certainly；Due to described
Suction-operated and the described effect of swallowing up effectively contained that therefore, dependence test result will be better able to objectively anti-
Reflect actual conditions；The effect of the low-power, high-frequency band ultrasonic wave, also include facilitating the reversible knot between antigen, antibody certainly
Close the quick of reaction to reach, this causes dependence test operation can be with than the completion of faster speed.
Due to surface chemical modification or chemistry for its relevant surfaces of the dimethyl silicone polymer substrate need not be carried out
Modified operation, therefore, this surface chemical modification layer or chemically modified layer not need to exist, then, the poly dimethyl
Its body phase interior polymer molecule of siloxanes substrate constantly diffuses to the surface automatically, migrate caused by it to the surface chemistry
The damaging influence of decorative layer or chemically modified layer is also just not present.
It is related that the technical scheme of this case has dissolved its application to dimethyl silicone polymer substrate addressed above totally
A series of technical barriers.Based on this case scheme, the very cheap polydimethyl siloxane material of this kind is just possible to micro- at this
It is prepared by fluidic chip, production, using etc. field play bigger effect.
Attached in the chain ring type magnetic holding device one magnetic conductivity link in this case structure it is fixed installed it is described miniature
Ultrasonic transducer, this architecture provides a function of facilitating the device to disassemble, in this way, the chain ring type magnetic holding device is together with it
The miniature ultrasonic transducer units attached in one magnetic conductivity link just easily can be mutually disengaged with the micro-fluidic chip, that
, the component that the part can freely depart from reuses many times in which just can circulate benignly；The architectural feature is advantageous to save
The use cost of the device.
Brief description of the drawings
Fig. 1 is the schematic diagram of this case device embodiment chip part construction, it is shown that the vertical view of this structure
The structural form of chip internal pipeline and each electrode and each related liquid pool under angle, the chain ring type is not depicted in the figure
Magnetic holding device and the miniature ultrasonic transducer units set up thereon and other annexes.
Fig. 2 be this case device chain ring type magnetic holding device its with appearance side rough under the micro-fluidic chip socket state
View, the legend and indicates the relative position relation under the socket state between each component.
Fig. 3 is the outside side view under another viewing angle of this case device；Fig. 3 viewing angle and Fig. 2's
Viewing angle is mutually perpendicular to.
In figure, 1,2,10 be the different liquid pool of three installation positions respectively, and 3 be manifold shape turnout, and 4,7,11,14 are respectively
Installation position is different but four laterals parallel with one another for forming UNICOM's structure in parallel, and 5 be its that be installed in lateral 4
Specific antigenic substance in the gold size sensitivity membrane structure of top layer is the working electrode of cholera TP0821 antigens, and 6 be to be installed in branch
The specific antigenic substance in its top layer gold size sensitivity membrane structure in pipeline 7 is the working electrode of cholera TP0319 antigens, 12
It is that specific antigenic substance in its top layer gold size sensitivity membrane structure being installed in lateral 11 is cholera TP0624 antigens
Working electrode, 13 be specific antigenic substance in its top layer gold size sensitivity membrane structure being installed in lateral 14 for suddenly
The working electrode of random O139 antigens, 8 be to electrode, and 9 be reference electrode, and 15 be chain ring type magnetic holding device, and 16 be the micro-fluidic core
The terminal of piece, 17 be the sample introduction end of the micro-fluidic chip, and 18 be the substrate of dimethyl silicone polymer material, and 19 be lid
Piece, 20 be miniature ultrasonic transducer units, and 21 be higher-order of oscillation electric signal transmission cable, and 22,29 be to be located at different structure position respectively
The link for the two magnetic conductivity materials put, the links of two magnetic conductivity materials end-to-end relation each other in the structure shown here, 23,32 points
It is not two pole shoes positioned at different structure position, 24,26,28,31,34,36 be six in six diverse locations respectively
Pin joint, 25,27,33,35 be the link of four non magnetic materials in four diverse locations respectively, and 30 be magnet exciting coil；
The chain ring type magnetic holding device structure in legend is only the legend structure of signal, and the actual chain ring type magnetic holding device structure is not limited to
The legend chain ring type magnetic holding device structure；Arrow in legend indicate the micro-fluidic chip its in actual motion, by two
End pressure difference driving, the flow direction of its sample liquid stream.
Embodiment
In this case that Fig. 1, Fig. 2 and Fig. 3 are shown embodiment, the structure of the micro fluidic device includes multichannel miniflow
Chip is controlled, the structure of the micro-fluidic chip includes being bonded to each other the substrate 18 and cover plate 19 of installing together, the He of substrate 18
Cover plate 19 is plate object or tablet, and that face towards the cover plate 19 of the substrate 18 is contained via mould pressing process or etching
Technique formed channel structure, the substrate 18 also containing be connected with the channel structure and pierce the substrate via stamper
The window structure that skill, etching technics or simple drilling technology are formed, it is bonded to each other the substrate 18 and the cover plate being installed together
19 have been built into the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto jointly, the liquid pool be liquid pool 1,
Liquid pool 2, liquid pool 10, the locations of structures of the pipeline are located at the interface zone that the substrate 18 is bonded to each other with the cover plate 19, the window
Its side is blocked by the cover plate 19 and opposite side opens, 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, two liquid pools therein be liquid pool 1 and liquid pool 2 its locations of structures to be located at this micro-
The sample introduction end 17 of fluidic chip, a remaining liquid pool are that liquid pool 10 its locations of structures is located at the actual sample introduction of the micro-fluidic chip and surveyed
The terminal 16 that liquid flows in its chip during examination, the terminal 16 are located remotely from each other with the sample introduction end 17, and one end of the pipeline is via same
Sample be located at the manifold shape turnout 3 of the interface zone being bonded to each other respectively with liquid pool 1 and the liquid pool 2 positioned at sample introduction end 17
Logical, the other end of the pipeline and a remaining liquid pool for the terminal 16 positioned at the micro-fluidic chip are liquid pool 10
It is logical, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode 8 and reference electrode 9, institute
It is quick by conductive electrode and the gold size for having embedded cholera specific antigen being attached on the conductive electrode to state working electrode
Feel film to form, 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 in four laterals, is somebody's turn to do respectively
Four working electrodes are working electrode 5, working electrode 6, working electrode 12, working electrode 13 respectively, and, this four work electricity
Specific antigen extremely in top layer gold size sensitivity membrane structure is that the four kinds of cholera that can be specifically bound to cholera antibody resist respectively
Original matter, four kinds of antigenic substances are cholera TP0821 antigens and cholera TP0319 antigens and cholera TP0624 antigens respectively
And cholera O139 antigens, for specifically deploying, 5 be in its top layer gold size sensitivity membrane structure being installed in lateral 4
Specific antigenic substance be cholera TP0821 antigens working electrode, 6 be that its top layer gold size being installed in lateral 7 is quick
Feel the working electrode that the specific antigenic substance in membrane structure is cholera TP0319 antigens, 12 are installed in lateral 11
Specific antigenic substance in its top layer gold size sensitivity membrane structure is the working electrode of cholera TP0624 antigens, and 13 be to be installed in point
The specific antigenic substance in its top layer gold size sensitivity membrane structure in branch pipe(tube) 14 is the working electrode of cholera O139 antigens, institute
It is gold material or thermal decomposition conducting polymer to state working electrode 5, working electrode 6, working electrode 12, working electrode 13 its material
Material, the working electrode 5, working electrode 6, working electrode 12, its pattern presentation sheet or thread of working electrode 13, emphasis
It is that its material of the substrate 18 is dimethyl silicone polymer material, its surface of substrate 18 is the surface of primary form, the primary shape
The surface of state its be intended to refer to the primary of the not no material by any surface chemical modification or any surface chemical modification
The surface of form, the structure of the device also include chain ring type magnetic holding device 15, are shared in its structure of the chain ring type magnetic holding device 15
Six links 22,25,27,29,33,35, the link 22,25,27,29,33,35 are each adjacent in strip, shaft-like or bar-shaped
Link is hinged to form chain link, the hexagonal cyclic structure of its appearance profile of the chain link, the hexagonal annular structure it is each
Drift angle is that drift angle 24,26,28,31,34,36 its locations of structures is articulated structure position, and the hexagonal annular structure is therein
Two links in opposite side position are that link 22,29 its material is magnetic conductivity material, the remainder four of the hexagonal annular structure
Individual link be link 25,27,33,35, its material be non-magnetic material, the non magnetic material refers to not having to externally-applied magnetic field
There is the material responded strongly, two links of the magnetic conductivity material are that a link among link 22,29 twines in link 29
Magnet exciting coil 30 is wound with, the link 29 for being wound with magnet exciting coil 30 is respectively installed in the both sides neighbor positions of its magnet exciting coil 30
There is the pole shoe of a magnetic conductivity material, share two pole shoes, the pole shoe is pole shoe 23 and pole shoe 32, and two pole shoes are
Pole shoe 23 and pole shoe 32 are directed to the link 22 of another magnetic conductivity material, its surface of the link 22 of another magnetic conductivity material
Upper attaching is fixed to be equiped with miniature ultrasonic transducer units 20, relies on the chain ring type magnetic holding device 15 socket of electromagnetism adhesive strength fixed
The close position of position its terminal 16 in the micro-fluidic chip, and, higher-order of oscillation electric signal transmission cable 21, the high frequency vibrating
The one end and the miniature ultrasonic transducer units 20 for swinging electric signal transmission cable 21 link together；The chain ring type magnetic holding device 15 carries
A function of facilitating the device to disassemble is supplied；Its major function of the miniature ultrasonic transducer units 20 is actual in micro-fluidic chip
When sample introduction is tested, the ultrasonic wave launched using it reduces the interfacial tension between sample solution and the inwall of the pipeline,
Can be compatible, also, utilize the sample introduction end 17 and the terminal 16 and the miniature ultrasonic transducer units 20 installing position
The distance between put the difference on difference and its ultrasonic intensity experienced, its interface of sample introduction end 17 described in induced synthesis
Difference between tension force and the terminal 16 its interfacial tension, the micro-fluidic chip both ends are between sample introduction end 17 and terminal 16
Interfacial tension difference can be to form pressure gap between sample introduction end 17 and terminal 16 at the both ends of the micro-fluidic chip, the pressure
Power difference can drive sample solution to be flowed to the direction of terminal 16；Its function of the miniature ultrasonic transducer units 20 also includes with it
The ultrasonic wave launched checks in sample contained its absorption on the inner surface of pipeline of large biological molecule, and then checks
Swallow up effect of its body phase of the substrate 18 of the dimethyl silicone polymer material to the large biological molecule；The dimethyl silicone polymer
The substrate 18 of material its function includes and cover plate 19 and working electrode 5, working electrode 6, working electrode 12, working electrode 13 and right
Electrode 8 and reference electrode 9 together build the micro-fluidic chip, the substrate of the dimethyl silicone polymer material that is soft and having elasticity
18 its function are also included with its property to the strong absorption of ultrasonic wave, and ultrasonic wave is absorbed strongly, and thereby in the miniflow
Control chip terminal 16 is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 17, its knot
Structure position is located at a remaining liquid for the terminal of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested
Pond is also referred to as terminal liquid pool, is filled with some high hydroscopic resin particles in the terminal liquid pool, and its opening end of the terminal liquid pool is breathed freely
Microporous barrier is covered.
Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, its try
The flow direction of sample liquid stream.
The chain ring type magnetic holding device 15 is depicted without in Fig. 1 and attaches fixation in one magnetic conductivity material link
Miniature ultrasonic transducer units 20 and higher-order of oscillation electric signal transmission cable 21 of installing；Also, in Fig. 1, Fig. 2 and Fig. 3
It is depicted without the associate members such as the higher-order of oscillation electric signal generator and multiple tracks electrochemical workstation.
Involved magnetic conductive material and involved nonmagnetic substance market are on sale.
Involved miniature ultrasonic transducer units 20 are commercially available；It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal transmission cable 21 is commercially available；Can also be special to ultrasonic transducer producer or cable
Industry producer customizes.
Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；It can also determine to relevant manufacturers
System.
Each working electrode in this example structure and can be respectively via each special electricity to electrode and reference electrode
Cable or say is being got lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as annex or saying interface connection of getting lines crossed.
This case device is that a variety of corresponding cholera antibody are detected with a variety of cholera antigens, thereby cholera diagnosis.
Claims (10)
1. sample liquid driving component is capable of the cholera diagnosis micro fluidic device of quick removal, the structure bag of the micro fluidic device
Multichannel micro-fluidic chip is included, the structure of the micro-fluidic chip includes being bonded to each other the substrate and cover plate of installing together, described
Substrate and cover plate are plate object or tablet, and that face towards the cover plate of the substrate is contained via mould pressing process or etching
Technique formed channel structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process,
The window structure that etching technics or simple drilling technology are formed, it is bonded to each other the substrate and the common structure of the cover plate being installed together
The micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto is built up, the locations of structures of the pipeline is located at the base
The interface zone that piece is bonded to each other with the cover plate, its side of the window is blocked by the cover plate and opposite side opens, the knot of the window
Structure position is exactly the locations of structures of the liquid pool, and the quantity of the liquid pool is three, its structure bit set of two liquid pools therein
In the sample introduction end of the micro-fluidic chip, when its locations of structures of a remaining liquid pool is located at the test of the micro-fluidic chip actual sample introduction
The terminal that liquid flows in its chip, the terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is via being similarly positioned in the phase
The manifold shape turnout for the interface zone being mutually bonded respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline with
Positioned at a remaining liquid pool UNICOM for the terminal of the micro-fluidic chip, and, sequentially it is respectively installed in the pipeline
Working electrode on diverse location and to electrode and reference electrode, the working electrode is by conductive electrode and is attached to
The gold size sensitive membrane for having embedded cholera specific antibody on the conductive electrode is formed, and the construction of the pipeline is in parallel construction,
The pipeline in parallel construction is made up of four lateral parallel connections, and the quantity of the working electrode is four, four works
The installation position for making electrode is located in four laterals respectively, and, its top layer gold size of four working electrodes is sensitive
Specific antigen in membrane structure is the four kinds of cholera antigenic substances that can be specifically bound to cholera antibody respectively, four kinds of antigens
Material is cholera TP0821 antigens and cholera TP0319 antigens and cholera TP0624 antigens and cholera O139 antigens respectively,
Its material of the working electrode is gold material or thermal decomposition conducting polymer material, and sheet is presented in its pattern of the working electrode
It is or thread, it is characterised in that its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is the table of primary form
Face, the surface of the primary form its be intended to refer to not by any surface chemical modification or any surface chemical modification should
The surface of the primary form of material, the structure of the device also include chain ring type magnetic holding device, its structure of the chain ring type magnetic holding device
In share six links, the link is in strip, shaft-like or bar-shaped, and each adjacent link is hinged to form chain link, the chain link
The hexagonal cyclic structure of its appearance profile, its locations of structures of each drift angle of the hexagonal annular structure is articulated structure position
Put, two therein of the hexagonal annular structure is magnetic conductivity material in the link of opposite side position its material, the hexagonal rings
Its material of the remaining four processes of shape structure is non-magnetic material, and the non magnetic material refers to not strong to externally-applied magnetic field
The material of strong response, magnet exciting coil is wound with a link among two links of the magnetic conductivity material, this, which is wound with, encourages
The link of magnetic coil is respectively equiped with the pole shoe of a magnetic conductivity material in the both sides neighbor positions of its magnet exciting coil, shares two
The pole shoe, two pole shoes are directed to the link of another magnetic conductivity material, its table of the link of another magnetic conductivity material
The fixed chain ring type magnetic holding device socket positioning for being equiped with miniature ultrasonic transducer units, relying on electromagnetism adhesive strength is attached on face
In the close position of its terminal of the micro-fluidic chip, and, higher-order of oscillation electric signal transmission cable, the higher-order of oscillation telecommunication
One end of number transmission cable links together with the miniature ultrasonic transducer units；The chain ring type magnetic holding device provides a convenience
The function that the device is disassembled；Its major function of the miniature ultrasonic transducer units is the profit in micro-fluidic chip actual sample introduction test
The ultrasonic wave launched with it reduces the interfacial tension between sample solution and the inwall of the pipeline, can be compatible,
Also, using the sample introduction end and the distance between the terminal and the miniature ultrasonic transducer units installation position difference and
Difference on its ultrasonic intensity experienced, its interfacial tension of sample introduction end described in induced synthesis and its interface of the terminal
Difference between power, the interfacial tension difference between the micro-fluidic chip both ends can be between the both ends of the micro-fluidic chip
Pressure gap is formed, the pressure gap can drive sample solution to the end flow；Its function of the miniature ultrasonic transducer units
Also include the ultrasonic wave launched with it and check contained its suction on the inner surface of pipeline of large biological molecule in sample
It is attached, and then check swallow up effect of its body phase of the substrate of the dimethyl silicone polymer material to the large biological molecule；Described poly- two
Its function of the substrate of methylsiloxane material is micro- including building with cover plate and working electrode and together this to electrode and reference electrode
Fluidic chip, it is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function also include it is strong to ultrasonic wave with it
The property of absorption, ultrasonic wave is absorbed strongly, and thereby in micro-fluidic chip terminal to having between the sample introduction end
The rapid decrement of ultrasonic intensity is realized within the short distance of limit, its locations of structures is located at the actual sample introduction test of the micro-fluidic chip
When its chip in the remaining liquid pool of terminal of liquid flowing be also referred to as terminal liquid pool, one is filled with the terminal liquid pool
A little high hydroscopic resin particles, its opening end of the terminal liquid pool are covered by breathable microporous film.
2. sample liquid driving component according to claim 1 is capable of the cholera diagnosis micro fluidic device of quick removal,
Characterized in that, the pipeline and the lateral and the manifold shape turnout are capillary channel.
3. sample liquid driving component according to claim 1 is capable of the cholera diagnosis micro fluidic device of quick removal,
Characterized in that, the thermal decomposition conducting polymer is the conduction formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated
Property material.
4. sample liquid driving component according to claim 1 is capable of the cholera diagnosis micro fluidic device of quick removal,
Characterized in that, the width or diameter of the working electrode be between 0.1 micron to 2000 microns, and, the work electricity
The length of pole is between 1 micron to 15000 microns.
5. sample liquid driving component according to claim 1 is capable of the cholera diagnosis micro fluidic device of quick removal,
Characterized in that, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. sample liquid driving component according to claim 1 is capable of the cholera diagnosis micro fluidic device of quick removal,
Characterized in that, the cover plate its material in structure is dimethyl silicone polymer material.
7. sample liquid driving component according to claim 1 is capable of the cholera diagnosis micro fluidic device of quick removal,
Characterized in that, positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal
Air line distance between a remaining liquid pool is between 3 centimetres and 7 centimetres.
8. sample liquid driving component according to claim 1 is capable of the cholera diagnosis micro fluidic device of quick removal,
Characterized in that, described its thickness of cover plate and substrate in structure is between 1.0 millimeters and 5.0 millimeters.
9. sample liquid driving component according to claim 1 is capable of the cholera diagnosis micro fluidic device of quick removal,
Characterized in that, the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal passes
Its other end of transmission cable is connected with the higher-order of oscillation electric signal generator.
10. sample liquid driving component according to claim 1 is capable of the cholera diagnosis micro fluidic device of quick removal,
Characterized in that, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units, between 5 milliwatts and 9000 milliwatts, this is micro-
The frequency of its ultrasonic wave operationally launched of type ultrasonic transducer is between 100KHz and 12MHz.
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