CN106990239A - The special cheap cholera diagnosis micro fluidic device of sap flow process mode - Google Patents
The special cheap cholera diagnosis micro fluidic device of sap flow process mode Download PDFInfo
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- CN106990239A CN106990239A CN201610065401.4A CN201610065401A CN106990239A CN 106990239 A CN106990239 A CN 106990239A CN 201610065401 A CN201610065401 A CN 201610065401A CN 106990239 A CN106990239 A CN 106990239A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56911—Bacteria
- G01N33/56916—Enterobacteria, e.g. shigella, salmonella, klebsiella, serratia
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/195—Assays involving biological materials from specific organisms or of a specific nature from bacteria
- G01N2333/28—Assays involving biological materials from specific organisms or of a specific nature from bacteria from Vibrionaceae (F)
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/06—Gastro-intestinal diseases
- G01N2800/065—Bowel diseases, e.g. Crohn, ulcerative colitis, IBS
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The present invention relates to a kind of special cheap cholera diagnosis micro fluidic device of sap flow process mode, belong to analysis testing field.The cheap and dimethyl silicone polymer i.e. PDMS that easily processes as being used for making the substrate of cholera diagnosis micro-fluidic chip if there is series problem；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
The present invention relates to a kind of special cheap cholera diagnosis micro fluidic device of sap flow process mode, belong to analysis testing field.
Background technology
The micro-fluidic cholera diagnostic techniques background of associated multi-channel, may refer to the invention patent application cases such as CN 200910150930.4.
Only for the microflow control technique overall general picture of itself, it may refer to the monograph " diagram Microfluid based Lab on a chip " that famous micro-fluidic expert Mr. Lin Ping Cheng goes out not long ago, the monograph is published via Science Press, the monograph to past of microflow control technique, now, and, in terms of vision of the future etc., long discussion that is detailed, being deep into detail is suffered from.
So, the Important Problems of this case that to have a talk below concern.
The basic framework of micro-fluidic chip, including the cover plate for being etched with the substrate of small fluid course and fitting together therewith, small fluid course on the substrate, before assembling upper cover plate, see to be exactly some micro-channels on apparent, will be after cover plate be covered thereon, just real closure forms the small fluid course, and the conduit inner surface of the micro-channel constitutes described small fluid course together with the part cover plate that surround the micro-channel；So, obviously, the small fluid course after assembling is completed, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, the state or property of the micro-channel inner surface substantially determine the integrality or property of the small fluid course；Therefore say, this inner surface state or inner surface property for building the micro-channel on substrate are key factors；In principle, any material that can be kept or keep its solid forms substantially, it can be used to make substrate and cover plate, such as, the material that can act as substrate and cover plate can be monocrystalline silicon piece, quartz plate, sheet glass, high polymer such as 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 the point of view of in terms of material consumption, manufacture difficulty and application popularization prospect etc., there is not small difference, the especially selection of that substrate between these materials, influence larger.
In various substrate making materials, dimethyl silicone polymer, that is PDMS, comparatively very easily shaping, making micro-channel is extremely simple on such substrate, and the lower cost for material, substrate is made 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, and 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 being extremely easy to popularize, promote.
But, thing is really not so simple.
One, this polydimethyl siloxane material, the material that i.e. abbreviation letter PDMS is referred to, itself it is 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, so, after overall assembling is completed, cover after cover plate, because the micro-channel its inner surface in structure occupies the inner surface of most fluid course, so, its strong hydrophobic property of the PDMS micro-channels inner surface, it 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, even general Micropump is all difficult to promote, certainly, if cover plate also selects to use the PDMS material, so, problem is substantially identical, it is 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, constitutes serious technical puzzlement, be another problem：PDMS polymer molecules inside its body phase of this PDMS material substrate have the characteristic for diffusing to the surface, migrating automatically, the characteristic that PDMS polymer molecules are diffused to the surface, migrated automatically inside this substrate body phase, the state after modification by its inner surface of that micro-channel of surface modifying and decorating will be caused can not to maintain the sufficiently long time, holding time for its inner surface state of the micro-channel after that is surface-modified is substantially only sufficient to the time needs for completing laboratory internal test experiments；In other words, by surface modification or the PDMS micro-channel inner surfaces of surface modification, the surface state that is formed can not be lasting after it is modified or after saying modification, but soon automatically tend to or say and become surface state before surface is modified again, and the strong hydrophobic surface state of that script is returned in the shorter time, so, just think, such micro-fluidic chip can largely make, mass storage, be widely popularized, and answer is apparent, that is, impossible.Micro-channel on this PDMS material, if not doing surface modification, can not pump and pass through similar to the fine liquid stream of polar solvent of the aqueous solution, chip also cannot just be used；And if having done surface modification, the state after its modification can not be persistently kept again, or equally can not popularization and application.
So, how to accomplish that substrate can either be made using cheap PDMS material, and can release the micro-channel inner surface decorating state can not persistently, chip can not largely make, largely lay in and then be widely popularized such a puzzlement for making the numerous professionals in this area be 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.
Secondly, 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 exactly, this strong hydrophobic PDMS surfaces can adsorb large biological molecule, also, these adsorbed large biological molecules can also further depression further on PDMS surfaces, gradually fall into gradually deep, until heavy be trapped within the body phase of PDMS substrates, in fact, this process, is partly also due to PDMS material body phase interior polymer molecule and has diffuse to the surface, caused by travel motion；Such case, it 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, it is little by little to be involved in those within the body phase of PDMS substrates by the large biological molecule of adsorption, briefly, these adsorbed large biological molecules are exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up the phenomenon of large biological molecule, and 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 be because surface saturation is adsorbed and stop, but, it is constantly adsorbed, also constantly swallowed up.
On PDMS substrates in related experiment test process its body phase constantly swallow up test associated biomolecule macromolecular phenomenon, another explanation is to say, there are substantial amounts of Minute pores in PDMS body phases, associated biomolecule macromolecular is by after adsorption, depression enters these Minute pores, and then is swallowed up；However, inventor thinks, those can allow that the air molecule of miniature scale 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 both difference on yardstick are huge, must not make sweeping generalizations.Explanation is bypassed, in any case, the large biological molecule for analyzing object as dependence test is adsorbed by PDMS substrate micro-channels inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is the phenomenon of known objective reality.
In order to prevent this PDMS substrate bodies relative to the effect of swallowing up of large biological molecule, the absorption of large biological molecule can be addressed from containment PDMS surfaces, method is chemically modified modification aiming at the PDMS material surface, for in the case of using PDMS as substrate material, modification exactly is chemically modified to the surface of described micro-channel part, the micro-channel inner surface being modified by chemical modification, its absorption to large biological molecule can be contained, and then avoid large biological molecule from being swallowed up by PDMS substrate body phases；But, or that old problem, that is exactly, surface state after chemical modification on PDMS material surface is modified can not persistently be kept, its process for diffusing to the surface, migrating automatically of polymer molecule inside the PDMS substrate body phases, that micro-channel inner surface state being modified by surface chemical modification soon can be become again to strong hydrophobic and strong adsorption large biological molecule the state of script, in other words, no matter how professionals in the field turn from side to side, and its micro-channel inner surface of the PDMS substrates 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, the absorption process for containing the PDMS substrate micro-channel inner surfaces for a long time to large biological molecule can be reached again, and then prevent the effect of swallowing up of PDMS substrate body Relative biological macromoleculars, it is exactly a very intractable problem so that related chip manufactured goods are able to maintain that a prolonged enough, rational shelf-life.The problem makes the numerous professionals in this area be entangled with, perplex for a long time as another problem addressed above, equally, 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 problems to be solved by the invention are, one package solution is provided, two problems addressed above are solved totally, and, the solution is used into multichannel micro-fluidic chip field applied to cholera diagnosis, a kind of new cholera diagnosis is formed and uses multichannel micro-fluidic device.
The present invention solves the technical problem by following scheme,The device that the program is provided is a kind of special cheap cholera diagnosis micro fluidic device of sap flow process mode,The structure of the micro fluidic device includes multichannel micro-fluidic chip,The structure of the micro-fluidic chip includes the substrate and cover plate of installing bonded to each other together,The substrate and cover plate are plate object or tablet,Contain the channel structure via mould pressing process or etching technics formation in that face towards the cover plate of the substrate,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 the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto jointly with the cover plate,The locations of structures of the pipeline is located at the substrate and cover plate interface zone bonded to each other,Its side of the window is blocked by the cover plate and opposite side is opened,The locations of structures of the window is exactly the locations of structures of the liquid pool,The quantity of the liquid pool is three,Its locations of structures of two liquid pools therein is located at the sample introduction end of the micro-fluidic chip,Its locations of structures of a remaining liquid pool is located at the terminal of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested,The terminal is located remotely from each other with the sample introduction end,One end of the pipeline via be similarly positioned in the manifold shape turnout of the interface zone bonded to each other respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end,The other end of the pipeline and a remaining liquid pool UNICOM for the terminal positioned at the micro-fluidic chip,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 made up of conductive electrode and the gold size sensitive membrane for having embedded cholera specific antigen being attached on the conductive electrode,The construction of the pipeline is in parallel construction,The pipeline in parallel construction is made up of four lateral parallel connections,The quantity of the working electrode is four,The installation position of four working electrodes is located in four laterals respectively,And,Specific antigen in the sensitive membrane structure of its top layer gold size of four working electrodes is the four kinds of cholera antigenic substances that can be specifically bound to cholera antibody respectively,Four kinds of antigenic substances are 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,Sheet or thread is presented in its pattern of the working electrode,Emphasis is,Its material of the substrate is dimethyl silicone polymer material,Its surface of the substrate is the surface of primary form,The surface of the primary form its be intended to refer to the material not no by any surface chemical modification or any surface chemical modification primary form surface,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 links together with the miniature ultrasonic transducer units,The miniature ultrasonic transducer units are installed in the position of the cover plate of the micro-fluidic chip or the neighbouring terminal of substrate with attaching；Its major function of the miniature ultrasonic transducer units is in the actual sample introduction test of micro-fluidic chip, the ultrasonic wave launched using it reduces the interfacial tension between sample solution and the inwall of the pipeline, can be compatible, and, utilize the difference on the distance between the sample introduction end and the terminal and miniature ultrasonic transducer units installation position difference and its ultrasonic intensity experienced, difference between its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension, interfacial tension difference between the micro-fluidic chip two ends can form pressure gap between the two ends of the micro-fluidic chip, the pressure gap can drive sample solution to the end flow；The miniature ultrasonic transducer units its functions also includes checking large biological molecule contained in sample its absorption on the inner surface of pipeline with its ultrasonic wave launched, and then checks swallow up effect of its body phase of the substrate of the dimethyl silicone polymer material to the large biological molecule；Its function of the substrate of the dimethyl silicone polymer material includes with cover plate and working electrode and together builds the micro-fluidic chip to electrode and reference electrode, it is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and also include with its property to the strong absorption of ultrasonic wave, ultrasonic wave is absorbed strongly, and the rapid decrement of ultrasonic intensity is thereby realized within micro-fluidic chip terminal to the limited short distance between the sample introduction end；And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；Its material of the ultrasonic wave damper is microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, the medial surface of each clamping limb is relative with the medial surface of another clamping limb, the medial surface of one of clamping limb is close to the sample introduction end of the micro-fluidic chip, the medial surface of another clamping limb is close to the ultrasonic wave damper, the elastic clip 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 strong consumption to ultrasonic energy that the ultrasonic wave damper is brought with its material, further the rapid decrement of ultrasonic intensity is realized in support within micro-fluidic chip terminal to the limited short distance between the sample introduction end, and thereby further expand the difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension.
The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and cholera specific antigen solution uniformly, with point sample instrument point sample or is coated on specified structure position, and forms its drying and forming-film.Cholera specific antigen in the gold size sensitive membrane is the cholera antigen of horseradish peroxidase or glucose oxidase mark, the gold size sensitive membrane has been included as fixing above-mentioned each cholera specific antigen and introducing complementary medium therein, and the complementary medium such as chitosan, cellulose acetate, gelatin be therein a kind of or their mixture.
The pipeline and the lateral and the manifold shape turnout in the microfluidic chip structure, its internal diameter size may each be arbitrarily selected size, but, for as far as possible less with the consideration in terms of prepare liquid sample and reduction reagent loss, the passage of capillary level is preferably selected on the pipeline and the lateral and the manifold shape turnout, and the passage of the capillary level implies that its internal diameter passage suitable with the internal diameter of the capillary on ordinary meaning.The shape of cross section of its inner passage of capillary can be arbitrary shape, the shape of cross section is for example circular, oval, square, rectangle, bar shaped, can certainly arbitrarily the presence of the linear of bending, and, the interior shape of the capillary is with the extension of pipeline, and the shape of cross section of different parts can also allow to be different shapes.Only for the word of capillary one, its art-recognized meanings is known.
What is be related in structure is the electrode of microsize to electrode and reference electrode, and its electrode shape may each be arbitrarily selected shape, the arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..The 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 pond shape or the scrotiform construction for transitional liquid storage, 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, and in order to use prepare liquid sample and reduction reagent loss less as far as possible, the liquid pool is preferably capable of the liquid pool of the microminiature matched with capillary.
It is known only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field.
Various sizes, variously-shaped ultrasonic transducer are commercially available；Its size of commercially available miniature ultrasonic transducer units may diminish to the magnitude only calculated with millimeter.
It is known general technology for the professional in ultrasonic technology field for itself only with regard to miniature ultrasonic transducer units its technique for fixing on general industry application solid body surface.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；Similarly, 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；Its other end of the higher-order of oscillation electric signal 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, is simple and known for the professional in ultrasonic technology field；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 is between 2 milliwatts and 2000 milliwatts；The preferred scope of the frequency of its ultrasonic wave operationally launched of the miniature ultrasonic transducer units is between 100KHz and 12MHz.
This case device can further include some annexes certainly, the annex such as multiple tracks electrochemical workstation etc., and the art-recognized meanings of the multiple tracks electrochemical workstation are known.Each working electrode for being related in this case microfluidic chip structure and to electrode and reference electrode etc., can respectively via it is corresponding it is special get lines crossed coupled with the corresponding interface of the multiple tracks electrochemical workstation.It is described that special to get lines crossed be private cable for each the corresponding interface of each electrode and the multiple tracks electrochemical workstation is coupled to each other.The micro-fluidic chip in this case device, its structure can also include micro-valve, and the quantity of the micro-valve 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 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, 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 allow 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 between 1 micron to 15000 microns.
The gold size sensitive membrane of the working electrode surface layer is installed in by spraying or point sample instrument point sample or the coating of other appropriate process, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness, it is however recommended to thickness preferred 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, for example：Polypropylene, glass, polymethyl methacrylate, dimethyl silicone polymer, etc., in order to make smaller size of micro-fluidic chip, such as make the micro-fluidic chip of the super-small of only 2.0 centimetres to 3.0 centimetres of length, and realize extremely fast decay to ultrasonic wave in the extremely short distance, can preferably dimethyl silicone polymer be used as cover plate.Certainly, select to be used as the cover plate using dimethyl silicone polymer on large-sized micro-fluidic chip, be also that this case technical scheme is allowed.
Positioned at two liquid pools at the sample introduction end of the micro-fluidic chip, itself and the air line distance between a remaining liquid pool for the micro-fluidic chip terminal can be arbitrarily selected suitable distance as needed, but, 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 the thickness for being easy to assembling, the thickness of recommendation or to say preferred 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 the arbitrary size set as needed.
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, among its application running of this case micro-fluidic chip, 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, driving liquid stream is flowed in the capillary channel of the four-way micro-fluidic chip, and four kinds of cholera antibody are detected respectively using four-way electrochemical analytical instrument.
Corresponding four kinds of cholera antibody is detected with four kinds of cholera antigens, four kinds of cholera antigens corresponding with being detected with four kinds of cholera antibody similarly, can cholera diagnosis；The principle of its foundation is, necessarily antigen, antibody and is deposited in cholera patient, and mutually Reversible binding, reversible conjugate is formed, therefore, antibody and thereby cholera diagnosis are detected with antigen, with removing detecting antigen and cholera diagnosis with antibody, diagnostic purpose can be reached.Certainly, its corresponding electrode sensitive decorative layer of different means technically and is differed.
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, the cholera specific antigen for the corresponding horseradish peroxidase-labeled that various cholera antibody molecules are embedded by gold size sensitive membrane on electrode surface in each passage is captured.
2nd, the cholera antibody formation immune complex in the cholera specific antigen and blood serum sample of horseradish peroxidase-labeled.
3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol is added, using curent change caused by the above-mentioned reaction of amperometric detection, the species and content of various analytes are derived from.
4th, result is subjected to comprehensive analysis, comprehensive diagnos is carried out to cholera antibody.
It is an advantage of the invention that, in the terminal of the micro-fluidic chip, its close position installs miniature ultrasonic transducer units with attaching, it is launched using the miniature ultrasonic transducer units low-power, the ultrasonic wave of high-frequency band, so that being significantly increased without the compatibility between strong hydrophobic its tube wall of micro-fluidic chip internal pipeline and the test object aqueous solution of surface chemical modification, this is test liquid stream by there is provided a realistic possibility；Simultaneously, utilize its strong absorbability to ultrasonic wave of dimethyl silicone polymer substrate, in shorter distance, namely, in from the terminal to the very short distance of only several centimeters yardsticks the sample introduction end, reach the rapid decrement of ultrasonic intensity, the difference of the interfacial tension is thereby caused at the two ends of the micro-fluidic chip, and then, using the pressure gap between its two ends for being formed of the difference of the interfacial tension between the two ends, 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 surface chemical modification or chemical modification must be carried out to the substrate and its internal pipeline of the dimethyl silicone polymer material, the laborious procedures of the surface chemical modification or chemical modification have been altogether dispensed with；And altogether dispense with the equipment of traditional Micropump etc；On the other hand, the ultrasonic wave of the low-power, high-frequency band, the absorption of large biological molecule in sample on literalness naked its inner surface of pipeline of dimethyl silicone polymer substrate can also be contained, and then contain the swallow up effect of its body phase of dimethyl silicone polymer substrate to the large biological molecule；The Reversible binding thing of the antigen, antibody and antigen and antibody is all the type for belonging to described large biological molecule certainly；Because described suction-operated and the described effect of swallowing up effectively are contained that therefore, dependence test result will be better able to objectively reflect actual conditions；The effect of the low-power, high-frequency band ultrasonic wave, also include facilitating certainly the Reversible binding between antigen, antibody react it is quick reach, this causes dependence 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 operation need not be carried out, therefore, this surface chemical modification layer or chemically modified layer not need to exist, so, its body phase interior polymer molecule of the dimethyl silicone polymer substrate constantly diffuses to the surface, migrates surface chemical modification layer or the damaging influence of chemically modified layer being also just not present caused by it automatically.
Its installation position of this case is located at the ultrasonic wave damper at the sample introduction end, the sport technique segment of ultrasonic intensity rapid decrement is realized in from its terminal of this case micro-fluidic chip to the such short distance in sample introduction end, the ultrasonic wave damper its function as the size expansion device of micro-fluidic chip, in other words, the ultrasonic wave damper its function as and significantly extend its terminal of micro-fluidic chip the distance between to sample introduction end, be 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, described terminal is relatively easily reached to the sport technique segment of the ultrasonic intensity rapid decrement between sample introduction end in short distance, and, the size expansion device namely the ultrasonic wave damper are torn open, it is convenient to fill, it is important that, it can also be reused.
The technical scheme of this case dissolved totally address above to dimethyl silicone polymer substrate its apply a series of related technical barriers.Based on this case scheme, this kind very cheap polydimethyl siloxane material is just possible to prepare in the micro-fluidic chip, 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, show in the structural form of the chip internal pipeline and each electrode and each related liquid pool under the depression angle of this structure, the figure and do not depict the miniature ultrasonic transducer units 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, 3 be manifold shape turnout, 4, 7, 11, 14 be that installation position is different but four laterals parallel with one another for forming UNICOM's structure in parallel respectively, 5 be the working electrode that specific antigenic substance in the sensitive membrane structure of its top layer gold size being installed in lateral 4 is cholera TP0821 antigens, 6 be the working electrode that specific antigenic substance in the sensitive membrane structure of its top layer gold size being installed in lateral 7 is cholera TP0319 antigens, 12 be the working electrode that specific antigenic substance in the sensitive membrane structure of its top layer gold size being installed in lateral 11 is cholera TP0624 antigens, 13 be the working electrode that specific antigenic substance in the sensitive membrane structure of its top layer gold size being installed in lateral 14 is cholera O139 antigens, 8 be to electrode, 9 be reference electrode, 15 be the substrate of dimethyl silicone polymer material, 16 be cover plate, 17 be higher-order of oscillation electric signal transmission cable, 18 be miniature ultrasonic transducer units, 19 be the sample introduction end of the micro-fluidic chip, 20 be the terminal of the micro-fluidic chip；Arrow in legend indicate 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 are plate object or tablet,Contain the channel structure via mould pressing process or etching technics formation in that face towards the cover plate 16 of the substrate 15,The substrate 15 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 15 bonded to each other being installed together has been built into the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto jointly with the cover plate 16,The liquid pool is 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,Its side of the window is blocked by the cover plate 16 and opposite side is opened,The locations of structures of the window is exactly the liquid pool 1,Liquid pool 2,The locations of structures of liquid pool 10,The quantity of the liquid pool is three,Two liquid pools therein are liquid pool 1 and its locations of structures of liquid pool 2 positioned at the sample introduction end 19 of the micro-fluidic chip,A remaining liquid pool is the terminal 20 that liquid flows in its chip when liquid pool 10 its locations of structures is located at the micro-fluidic chip actual sample introduction test,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 the liquid pool 1 positioned at sample introduction end 19 and the UNICOM of liquid pool 2,A remaining liquid pool for the terminal 20 of the other end of the pipeline with being located at the micro-fluidic chip is the UNICOM of liquid pool 10,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 made up of conductive electrode and the gold size sensitive membrane for having embedded cholera specific antigen being attached on the conductive electrode,The construction of the pipeline is in parallel construction,The pipeline in parallel construction is made up of four lateral parallel connections,The quantity of the working electrode is four,The installation position of four working electrodes is located in four laterals respectively,Four working electrodes are working electrode 5 respectively,Working electrode 6,Working electrode 12,Working electrode 13,And,Specific antigen in the sensitive membrane structure of its top layer gold size of four working electrodes is the four kinds of cholera antigenic substances that can be specifically bound to cholera antibody respectively,Four kinds of antigenic substances are cholera TP0821 antigens and cholera TP0319 antigens and cholera TP0624 antigens and cholera O139 antigens respectively,For specifically deploying,5 be the working electrode that specific antigenic substance in the sensitive membrane structure of its top layer gold size being installed in lateral 4 is cholera TP0821 antigens,6 be the working electrode that specific antigenic substance in the sensitive membrane structure of its top layer gold size being installed in lateral 7 is cholera TP0319 antigens,12 be the working electrode that specific antigenic substance in the sensitive membrane structure of its top layer gold size being installed in lateral 11 is cholera TP0624 antigens,13 be the working electrode that specific antigenic substance in the sensitive membrane structure of its top layer gold size being installed in lateral 14 is cholera O139 antigens,The working electrode 5,Working electrode 6,Working electrode 12,Its material of working electrode 13 is gold material or thermal decomposition conducting polymer material,The working electrode 5,Working electrode 6,Working electrode 12,Sheet or thread is presented in its pattern of working electrode 13,Emphasis is,Its material of the substrate 15 is dimethyl silicone polymer material,Its surface of substrate 15 is the surface of primary form,The surface of the primary form its be intended to refer to the material not no by any surface chemical modification or any surface chemical modification primary form surface,The structure of the micro fluidic device also includes miniature ultrasonic transducer units 18,And,Higher-order of oscillation electric signal transmission cable 17,One end of the higher-order of oscillation electric signal transmission cable 17 links together with the miniature ultrasonic transducer units 18,The miniature ultrasonic transducer units 18 are installed in the position of the cover plate 16 of the micro-fluidic chip or the neighbouring terminal 20 of substrate 15 with attaching；Its major function of the miniature ultrasonic transducer units 18 is in the actual sample introduction test of micro-fluidic chip, the ultrasonic wave launched using it reduces the interfacial tension between sample solution and the inwall of the pipeline, can be compatible, and, utilize the difference on the distance between the sample introduction end 19 and the terminal 20 and the installation position of miniature ultrasonic transducer units 18 difference and its ultrasonic intensity experienced, difference between its interfacial tension of sample introduction end 19 described in induced synthesis and the terminal 20 its interfacial tension, the micro-fluidic chip two ends are that the interfacial tension difference between sample introduction end 19 and terminal 20 can form pressure gap between the two ends of the micro-fluidic chip i.e. sample introduction end 19 and terminal 20, the pressure gap can drive sample solution to be flowed to the direction of terminal 20；Its function of the miniature ultrasonic transducer units 18 also includes checking large biological molecule contained in sample its absorption on the inner surface of pipeline with its ultrasonic wave launched, and then checks swallow up effect of its body phase of the substrate 15 of the dimethyl silicone polymer material to the large biological molecule；The substrate 15 of the dimethyl silicone polymer material its function includes and cover plate 16 and working electrode 5, working electrode 6, working electrode 12, working electrode 13 and together builds the micro-fluidic chip to electrode 8 and reference electrode 9, it is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and also include with its property to the strong absorption of ultrasonic wave, ultrasonic wave is absorbed strongly, and the rapid decrement of ultrasonic intensity is thereby realized within micro-fluidic chip terminal to the limited short distance between the sample introduction end；And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；Its material of the ultrasonic wave damper is microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, the medial surface of each clamping limb is relative with the medial surface of another clamping limb, the medial surface of one of clamping limb is 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 strong consumption to ultrasonic energy that the ultrasonic wave damper is brought with its material, further the rapid decrement of ultrasonic intensity is realized in support within micro-fluidic chip terminal 20 to the limited short distance between the sample introduction end 19, and thereby further expand the difference between described its interfacial tension of sample introduction end 19 and the terminal 20 its interfacial tension.It is depicted without being also depicted without the elastic clip in the ultrasonic wave damper, legend in legend.
Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, the flow direction of its test liquid stream.
Miniature ultrasonic transducer units 18 and higher-order of oscillation electric signal transmission cable 17 are depicted without in Fig. 1；Also, the associate members such as the higher-order of oscillation electric signal generator and multiple tracks electrochemical workstation are depicted without in Fig. 1 and 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 can get lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as annex or saying interface of getting lines crossed and coupling via each special cable or say respectively.
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. the special cheap cholera diagnosis micro fluidic device of sap flow process mode,The structure of the micro fluidic device includes multichannel micro-fluidic chip,The structure of the micro-fluidic chip includes the substrate and cover plate of installing bonded to each other together,The substrate and cover plate are plate object or tablet,Contain the channel structure via mould pressing process or etching technics formation in that face towards the cover plate of the substrate,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 the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto jointly with the cover plate,The locations of structures of the pipeline is located at the substrate and cover plate interface zone bonded to each other,Its side of the window is blocked by the cover plate and opposite side is opened,The locations of structures of the window is exactly the locations of structures of the liquid pool,The quantity of the liquid pool is three,Its locations of structures of two liquid pools therein is located at the sample introduction end of the micro-fluidic chip,Its locations of structures of a remaining liquid pool is located at the terminal of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested,The terminal is located remotely from each other with the sample introduction end,One end of the pipeline via be similarly positioned in the manifold shape turnout of the interface zone bonded to each other respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end,The other end of the pipeline and a remaining liquid pool UNICOM for the terminal positioned at the micro-fluidic chip,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 made up of conductive electrode and the gold size sensitive membrane for having embedded cholera specific antibody being attached on the conductive electrode,The construction of the pipeline is in parallel construction,The pipeline in parallel construction is made up of four lateral parallel connections,The quantity of the working electrode is four,The installation position of four working electrodes is located in four laterals respectively,And,Specific antigen in the sensitive membrane structure of its top layer gold size of four working electrodes is the four kinds of cholera antigenic substances that can be specifically bound to cholera antibody respectively,Four kinds of antigenic substances are 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,Sheet or thread is presented in its pattern of the working electrode,It is characterized in that,Its material of the substrate is dimethyl silicone polymer material,Its surface of the substrate is the surface of primary form,The surface of the primary form its be intended to refer to the material not no by any surface chemical modification or any surface chemical modification primary form surface,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 links together with the miniature ultrasonic transducer units,The miniature ultrasonic transducer units are installed in the position of the cover plate of the micro-fluidic chip or the neighbouring terminal of substrate with attaching；Its major function of the miniature ultrasonic transducer units is in the actual sample introduction test of micro-fluidic chip, the ultrasonic wave launched using it reduces the interfacial tension between sample solution and the inwall of the pipeline, can be compatible, and, utilize the difference on the distance between the sample introduction end and the terminal and miniature ultrasonic transducer units installation position difference and its ultrasonic intensity experienced, difference between its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension, interfacial tension difference between the micro-fluidic chip two ends can form pressure gap between the two ends of the micro-fluidic chip, the pressure gap can drive sample solution to the end flow；The miniature ultrasonic transducer units its functions also includes checking large biological molecule contained in sample its absorption on the inner surface of pipeline with its ultrasonic wave launched, and then checks swallow up effect of its body phase of the substrate of the dimethyl silicone polymer material to the large biological molecule；Its function of the substrate of the dimethyl silicone polymer material includes with cover plate and working electrode and together builds the micro-fluidic chip to electrode and reference electrode, it is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and also include with its property to the strong absorption of ultrasonic wave, ultrasonic wave is absorbed strongly, and the rapid decrement of ultrasonic intensity is thereby realized within micro-fluidic chip terminal to the limited short distance between the sample introduction end；And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；Its material of the ultrasonic wave damper is microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic force accompanies two clamping limbs, the medial surface of each clamping limb is relative with the medial surface of another clamping limb, the medial surface of one of clamping limb is close to the sample introduction end of the micro-fluidic chip, the medial surface of another clamping limb is close to the ultrasonic wave damper, the elastic clip 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 strong consumption to ultrasonic energy that the ultrasonic wave damper is brought with its material, further the rapid decrement of ultrasonic intensity is realized in support within micro-fluidic chip terminal to the limited short distance between the sample introduction end, and thereby further expand the difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension.
2. the special cheap cholera diagnosis micro fluidic device of sap flow process mode according to claim 1, it is characterised in that the pipeline and the lateral and the manifold shape turnout are capillary channel.
3. the special cheap cholera diagnosis micro fluidic device of sap flow process mode according to claim 1, it is characterised in that the thermal decomposition conducting polymer be by polyimides or polyacrylonitrile be heat-treated through anoxybiotic after the conductive material that is formed.
4. the special cheap cholera diagnosis micro fluidic device of sap flow process mode according to claim 1, it is characterized in that, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the length of the working electrode is between 1 micron to 15000 microns.
5. the special cheap cholera diagnosis micro fluidic device of sap flow process mode according to claim 1, it is characterised in that the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. the special cheap cholera diagnosis micro fluidic device of sap flow process mode according to claim 1, it is characterised in that its material of the cover plate in structure is dimethyl silicone polymer material.
7. the special cheap cholera diagnosis micro fluidic device of sap flow process mode according to claim 1, characterized in that, positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with the air line distance between a remaining liquid pool for the micro-fluidic chip terminal between 3 centimetres and 7 centimetres；The cover plate in structure and substrate its thickness are between 1.0 millimeters and 5.0 millimeters.
8. the special cheap cholera diagnosis micro fluidic device of sap flow process mode according to claim 1, it is characterised in that the microcellular rubber is micropore silicon rubber or micropore fluorubber.
9. the special cheap cholera diagnosis micro fluidic device of sap flow process mode according to claim 1, it is characterized in that, the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, and its other end of the higher-order of oscillation electric signal transmission cable is connected with the higher-order of oscillation electric signal generator.
10. the special cheap cholera diagnosis micro fluidic device of sap flow process mode according to claim 1, it is characterized in that, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 2 milliwatts and 2000 milliwatts, and the frequency of its ultrasonic wave operationally launched of the miniature ultrasonic transducer units is between 100KHz and 12MHz.
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