CN107085101A - Strong hydrophobic PDMS as substrate material hypotype swine flu detection chip apparatus - Google Patents

Strong hydrophobic PDMS as substrate material hypotype swine flu detection chip apparatus Download PDF

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Publication number
CN107085101A
CN107085101A CN201610100297.8A CN201610100297A CN107085101A CN 107085101 A CN107085101 A CN 107085101A CN 201610100297 A CN201610100297 A CN 201610100297A CN 107085101 A CN107085101 A CN 107085101A
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China
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micro
substrate
fluidic chip
swine flu
hypotype swine
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Chinese (zh)
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李榕生
葛宇杰
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Individual
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56983Viruses

Abstract

The present invention relates to a kind of strong hydrophobic PDMS as the hypotype swine flu detection chip apparatus of substrate material, belong to analysis testing field.There is many obstacles using dimethyl silicone polymer i.e. PDMS that is cheap and easily processing to make the substrate of hypotype swine flu diagnosis micro-fluidic chip;Its surface of the PDMS material is strongly hydrophobic, and targetedly surface is modified or surface modification, and its effect is difficult to persistently, and this case aims to solve the problem that the serial relevant issues.This case main points are, the selected PDMS with ecosystem surface of substrate, and fastening is positioned at the test liquid stream terminal of the micro-fluidic chip its neighbor positions manually by the hinge-type fixture for being attached to miniature ultrasonic transducer units, simultaneously, ultrasonic wave damper is installed at the sample introduction end of the micro-fluidic chip, reach ultrasonic intensity rapid decrement in short distance, so as to form interfacial tension difference at the two ends of the chip, thereby facilitate test liquid stream to be flowed along originally hydrophobic capillary channel to the terminal direction.

Description

Strong hydrophobic PDMS as substrate material hypotype swine flu detection chip apparatus
Technical field
The present invention relates to a kind of hypotype swine flu detection chip apparatus of strong hydrophobic PDMS as substrate material, belong to analysis and survey Examination field.
Background technology
Multichannel micro-fluidic hypotype swine flu diagnostic techniques background, may refer to the patent of invention such as CN 201110311127.1 Shen Please case.
Only for the microflow control technique overall general picture of itself, it may refer to famous micro-fluidic expert Mr. Lin Ping Cheng and go out not long ago Monograph " diagram Microfluid based Lab on a chip ", the monograph is published via Science Press, and the monograph is to microflow control technique Past, now, and, in terms of vision of the future etc., suffer from detail, be deep into long discussion of detail.
So, the Important Problems of this case that to have a talk below concern.
The basic framework of micro-fluidic chip, including it is etched with the substrate of small fluid course and the cover plate fit together therewith, Small fluid course on the substrate, assembling upper cover plate before, it is apparent on see to be exactly some micro-channels, wait until thereon After covering cover plate, just real closure forms the small fluid course, and the conduit inner surface of the micro-channel is together with surround this The part cover plate of micro-channel constitutes described small fluid course together;So, it is clear that this after assembling is completed is small Fluid course, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, in the micro-channel The state or property on surface substantially determine the integrality or property of the small fluid course;Therefore say, this is built in base The inner surface state or inner surface property of micro-channel on piece are key factors;In principle, it is any to keep or protecting substantially The material of its solid forms is held, can be used to make substrate and cover plate, such as, the material that can act as substrate and cover plate can be with It is monocrystalline silicon piece, quartz plate, sheet glass, high polymer such as dimethyl silicone polymer, polymethyl methacrylate, makrolon etc. Deng;Certainly, the selection of substrate and the selection of cover plate be able to can also be differed with identical;From material consumption, manufacture difficulty and From the point of view of in terms of application popularization prospect etc., between these materials exist not small difference, the especially selection of that substrate, influence compared with Greatly.
In various substrate making materials, dimethyl silicone polymer, i.e. PDMS, comparatively very easily shaping, so Substrate on make that micro-channel is extremely simple, and the lower cost for material makes substrate with the polydimethyl siloxane material, Micro-channel is being suppressed or etched thereon, and is being engaged with the cover plate that the cheap material such as glass or polypropylene or other plastic sheets makes, It is a kind of more satisfactory selection seemingly;Certainly, patch material can also select to use cheap polydimethyl siloxane material: So, this substrate selection is the scheme of polydimethyl siloxane material, and material is extremely cheap, makes extremely simple, seems and should also be as It is extremely easy to popularize, promotes.
But, thing is really not so simple.
First, this polydimethyl siloxane material, that is, the material that the letter PDMS that abridges is referred to, itself are a kind of strong Hydrophobic material, micro-channel is built on this material, if without being operated for the modified of the micro-channel surface, then, After overall assembling is completed, that is, cover after cover plate, because the micro-channel its inner surface in structure occupies most liquid circulation The inner surface in road, then, its strong hydrophobic property of the PDMS micro-channels inner surface, is deciding factor, it can cause class Be similar to the aqueous solution the fine liquid stream of polar liquid by becoming very difficult, its flow resistance is big, or even general Micropump is all It is difficult to promote, certainly, if cover plate also selects to use the PDMS material, then, problem is substantially identical, similar; Therefore, among prior art, modification is modified particular for the micro-channel inner surface on the PDMS material, is necessary Operation;So, this is pretty troublesome for the modified operation of PDMS micro-channel inner surfacesThat falls nor this problem, structure Perplex into serious technical, be another problem:PDMS polymer molecules tool inside its body phase of this PDMS material substrate There are PDMS polymer molecules inside the characteristic for diffusing to the surface, migrating automatically, this substrate body phase to diffuse to the surface, move automatically The characteristic of shifting, will cause the state after modification by its inner surface of that micro-channel of surface modifying and decorating can not maintain foot Enough long time, the holding time for micro-channel its inner surface state after that is surface-modified is substantially only sufficient to complete in laboratory The time of portion's test experiments needs;In other words, by surface modification or the PDMS micro-channel inner surfaces of surface modification, its The surface state that is formed can not be lasting after modification or after saying modification, but soon automatically tend to or say and become surface again and change Surface state before property, returns to the strong hydrophobic surface state of that script in the shorter time, then, just think, Such micro-fluidic chip can largely make, mass storage, be widely popularized, and answer is it is obvious that is, impossible. Micro-channel on this PDMS material, can not pump similar to the fine liquid stream of polar solvent of the aqueous solution if not doing surface modification Send and pass through, chip also cannot just be used;And if having done surface modification, the state after its modification can not be persistently kept again, also Being equally can not popularization and application.
So, how to accomplish that substrate can either be made using cheap PDMS material, and table in the micro-channel can be released Face decorating state can not persistently, chip can not largely make, largely lay in so that be widely popularized it is such a make this area it is numerous specially The puzzlement that industry personnel are entangled with for a long time, the highly difficult problem that exactly one its obvious technology barrier can not despise.
Be present many year in the highly difficult problem, so far, not yet properly settled.
Second, the PDMS material of non-surface modification, above it is stated that, its surface is strongly hydrophobic, this strong hydrophobic Material surface and also another problem, that is, this strong hydrophobic PDMS surfaces can adsorb large biological molecule, and And, these adsorbed large biological molecules can also further depression further on PDMS surfaces, gradually fall into gradually deep, directly It is trapped in heavy within the body phase of PDMS substrates, in fact, this process is partly also due to inside PDMS material body phase Polymer molecule, which has, to be diffused to the surface, caused by travel motion;Such case, can also be explained from another angle, i.e. Continuously from inside PDMS body phases to its diffusion into the surface, migration those polymer molecules, its result moved, be by Gradually those are involved within the body phase of PDMS substrates by the large biological molecule of adsorption, briefly, these are inhaled Attached large biological molecule is exactly to be swallowed up by PDMS substrate body phases;So, this PDMS substrates body phase swallows up large biological molecule Phenomenon, the influence caused by it necessarily causes the severe deviations of all kinds of test data of experiment for being related to large biological molecule.
As described above, be the problem of PDMS substrates, its not only adsorption large biological molecule, and swallow up large biological molecule, So, as the large biological molecule of experiment test object, its disappearance will not stop because the absorption of surface saturation, but, no It is disconnected adsorbed, also constantly swallowed up.
On PDMS substrates in related experiment test process its body phase constantly swallow up test associated biomolecule macromolecular phenomenon, separately It is to say that one kind, which is explained, there are substantial amounts of Minute pores in PDMS body phases, and associated biomolecule macromolecular is by after adsorption, depression Into these Minute pores, and then swallowed up;However, inventor thinks, those can allow the air point of miniature scale Son squeezes into the Minute pores therebetween, and being not equal to them also can directly allow that the large biological molecule of relative large scale enters, and two Person's difference on yardstick is huge, must not make sweeping generalizations.Explanation is bypassed, in any case, the biology of object is analyzed as dependence test Macromolecular is adsorbed by PDMS substrate micro-channels inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is known objective The phenomenon of presence.
, can be from containment PDMS surfaces to life in order to prevent this PDMS substrate bodies relative to the effect of swallowing up of large biological molecule The absorption of thing macromolecular is addressed, and method is chemically modified modification aiming at the PDMS material surface, for For PDMS is the situation of substrate material, modification exactly is chemically modified to the surface of described micro-channel part, by changing The micro-channel inner surface of modification is learned, its absorption to large biological molecule can be contained, and then avoid large biological molecule quilt PDMS substrate body phases are swallowed up;But, or that old problem, that is, the chemical modification on PDMS material surface changes Surface state after property can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface automatically, The process of migration, soon can become that micro-channel inner surface state being modified by surface chemical modification again script strong and dredge Water and the state of strong adsorption large biological molecule, in other words, no matter how professionals in the field turn from side to side, the PDMS Its micro-channel inner surface of substrate is always rapidly to strong hydrophobic surface state evolution.
So, how can either obtain that PDMS material price is extremely cheap, substrate makes extremely easy benefit, can reach again Growth stage contains absorption process of the PDMS substrate micro-channel inner surfaces to large biological molecule, and then prevents PDMS substrate body phases The effect of swallowing up to large biological molecule so that related chip manufactured goods are able to maintain that a prolonged enough, rational shelf-life, It is exactly a very intractable problem.The problem makes the numerous specialties in this area as another problem addressed above, equally Personnel are entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise.The hardly possible Also be present many year in topic, so far, also not yet properly settled.
The content of the invention
The technical problems to be solved by the invention are to provide a package solution, solve what is addressed above totally Two problems, also, the solution is used into multichannel micro-fluidic chip field applied to hypotype swine flu diagnosis, form a kind of New hypotype swine flu diagnosis Multichannel device.
The present invention solves the technical problem by following scheme, and the device that the program is provided is a kind of strong hydrophobic PDMS as base The hypotype swine flu detection chip apparatus of piece material, the structure of the device includes multichannel micro-fluidic chip, the micro-fluidic chip Structure include installing substrate and cover plate together bonded to each other, the substrate and cover plate are plate object or tablet, the base The channel structure via mould pressing process or etching technics formation is contained in that face towards the cover plate of piece, and the substrate also contains and this Channel structure is connected and pierces the window structure via the formation of mould pressing process, etching technics or simple drilling technology of the substrate, Substrate bonded to each other being installed together has been built into containing pipeline configuration and the liquid pool knot being attached thereto jointly with the cover plate The micro-fluidic chip of structure, the locations of structures of the pipeline is located at the substrate and cover plate interface zone bonded to each other, the window one Side is blocked by the cover plate and opposite side is opened, and the locations of structures of the window is exactly the locations of structures of the liquid pool, the number of the liquid pool Amount is three, and its locations of structures of two liquid pools therein is located at the sample introduction end of the micro-fluidic chip, its structure of a remaining liquid pool Position is located at the terminal of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, and the terminal and the sample introduction end are mutually remote From, the pipeline one end via be similarly positioned in the manifold shape turnout of the interface zone bonded to each other respectively with positioned at sample introduction end should Liang Ge liquid pools UNICOM, 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 work Electrode is sensitive by conductive electrode and the gold size for having embedded hypotype swine flu specific antigen being attached on the conductive electrode Film is constituted, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of three lateral parallel connections, described The quantity of working electrode is three, and the installation position of three working electrodes is located in three laterals respectively, and, Specific antigen in the sensitive membrane structure of its top layer gold size of three working electrodes is respectively can specificity to hypotype swine flu antibody With reference to three kinds of hypotype swine flu antigenic substances, three kinds of antigenic substances are hypotype swine flu specific antigen H respectively1N1、H3N2 And H1N2, its material of the working electrode is gold material or thermal decomposition conducting polymer material, and its pattern of the working electrode is in Existing sheet or thread, emphasis is that its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is primary form Surface, the surface of the primary form its be intended to refer to not by any surface chemical modification or any surface chemical modification should The surface of the primary form of material, the structure of the device also includes hinge-type fixture, and hinge-type fixture its appearance profile likeness in form is closed Page, the hinge-type fixture is by two hinges being mutually hinged and through a fastening screw of two hinges and one The individual nut for being used for fastening and hand break loose manually for matching and being connected together with the fastening screw with the fastening screw is constituted, should Two hinges of hinge-type fixture are respectively mutually drawn close with its tip and clamp the micro-fluidic chip, and it is micro-fluidic that the tip is positioned at this Fixation, which is attached, in the locations of structures of the neighbouring terminal of chip, in a hinge at least in is equiped with miniature ultrasonic Wave transducer, and, higher-order of oscillation electric signal transmission cable, one end of the higher-order of oscillation electric signal transmission cable is miniature super with this Acoustic wave transducer links together;The hinge-type fixture facilitates the function that the device is disassembled there is provided one;The miniature ultrasonic is changed Can device its major function be in the actual sample introduction test of micro-fluidic chip, the ultrasonic wave launched using it reduce sample solution and Interfacial tension between the inwall of the pipeline, can be compatible, also, using the sample introduction end and the terminal with being somebody's turn to do Difference in the distance between miniature ultrasonic transducer units installation position difference and its ultrasonic intensity experienced, induces shape Boundary between difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension, the micro-fluidic chip two ends Face tension difference can form pressure gap between the two ends of the micro-fluidic chip, and the pressure gap can drive sample solution to institute State end flow;Its function of the miniature ultrasonic transducer units also includes checking life contained in sample with its ultrasonic wave launched Its absorption on the inner surface of pipeline of thing macromolecular, and then check the substrate of the dimethyl silicone polymer material its body phase to this The effect of swallowing up of large biological molecule;The substrate of the dimethyl silicone polymer material its function includes and cover plate and working electrode and right Electrode and reference electrode together build the micro-fluidic chip, soft and have the substrate of the dimethyl silicone polymer material of elasticity its work( Can also include, with its property to the strong absorption of ultrasonic wave, ultrasonic wave being absorbed strongly, and thereby the micro-fluidic chip this Terminal is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end;And, ultrasonic wave damper, Its profile of ultrasonic wave damper is in block, tabular or bar-shaped;Its material of the ultrasonic wave damper 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 with it is another The medial surface of individual clamping limb is relative, and the medial surface of one of clamping limb is close to the sample introduction end of the micro-fluidic chip, another folder The medial surface of gripping arm is close to the ultrasonic wave damper, and the elastic clip is with its gripping strength by the sample introduction end of the micro-fluidic chip with being somebody's turn to do Ultrasonic wave damper is clipped together bonded to each otherly, the strong abatement to ultrasonic wave that the ultrasonic wave damper is brought with its material Effect, further supports to realize that ultrasonic wave is strong within micro-fluidic chip terminal to the limited short distance between the sample introduction end The rapid decrement of degree, and thereby further expand the difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension It is different.
Described miniature ultrasonic transducer units can certainly be all installed in two hinges;But, only installing one is micro- Type ultrasonic transducer is dealt with enough to be used.
The word of hinge one art-recognized meanings of itself are known.
The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and hypotype swine flu specific antibody solution uniformly, is used Point sample instrument point sample is coated on specified structure position, and forms its drying and forming-film.Hypotype swine flu in the gold size sensitive membrane Specific antibody is the hypotype swine flu antibody of horseradish peroxidase or glucose oxidase mark, the gold size sensitive membrane It has been included as fixing above-mentioned each hypotype swine flu specific antibody and introducing complementary medium therein, the complementary medium is for example Chitosan, cellulose acetate, gelatin be therein a kind of or their mixture.
The pipeline and the lateral and the manifold shape turnout in the microfluidic chip structure, its internal diameter chi It is very little to may each be arbitrarily selected size, still, use the consideration in terms of prepare liquid sample and reduction reagent loss less for trying one's best, The passage of capillary level, the capillary level are preferably selected in the pipeline and the lateral and the manifold shape turnout Passage imply that its internal diameter passage suitable with the internal diameter of the capillary on ordinary meaning.Its inner passage of capillary it is transversal Face shape can be arbitrary shape, the shape of cross section is for example circular, oval, square, rectangle, bar shaped, certainly Can be arbitrarily exist bending it is linear, also, the capillary interior shape with the extension of pipeline, different parts Shape of cross section can also allow to be different shapes.Only for the word of capillary one, its art-recognized meanings is known.
What is be related in structure is the electrode of microsize to electrode and reference electrode, and its electrode shape may each be any choosing Fixed shape, the arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..It is described to electricity The art-recognized meanings of pole and the reference electrode vocabulary of itself are known.
It is related to several liquid pools in this case microfluidic chip structure, the liquid pool is the pond shape or scrotiform structure for transitional liquid storage Make, its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, the cavity shape such as cylindrical empty Cavity-like, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..The size of the liquid pool can be arbitrarily selected Size, still, in order to use prepare liquid sample and reduction reagent loss less as far as possible, the liquid pool is preferably capable of and capillary The liquid pool of the microminiature of matching.
It is public only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field Know.
Various sizes, variously-shaped ultrasonic transducer are commercially available;Commercially available miniature ultrasonic transducer units its sizes can be with It is small to the magnitude only calculated with millimeter.
Only with regard to miniature ultrasonic transducer units its technique for fixing on general industry application solid body surface itself and Speech, is known general technology for the professional in ultrasonic technology field.This case is not to this expansion superfluous words.
Only with regard to naked PDMS substrates itself micro-channel molding or lithographic technique for, be open-and-shut known technology;Together Sample, the technology of hole-opening is even more known simple technique on naked PDMS substrates.This case is not also to this expansion superfluous words.
The industrial products market of involved its all size of higher-order of oscillation electric signal transmission cable is on sale.
The structure of the device can also include higher-order of oscillation electric signal generator;Its is another for the higher-order of oscillation electric signal transmission cable One end can be connected with the higher-order of oscillation electric signal generator.
The involved higher-order of oscillation electric signal generator technology of itself, for the professional in ultrasonic technology field, be It is simple and known;The higher-order of oscillation electric signal generator can be customized to ultrasonic instrument specialized factory.
The preferred scope of its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units be between 5 milliwatts and 9000 milliwatts it Between;The preferred scope of the frequency of its ultrasonic wave operationally launched of the miniature ultrasonic transducer units be between 100KHz with Between 12MHz.
This case device can further include some annexes, the annex such as multiple tracks electrochemical workstation etc., institute certainly The art-recognized meanings for stating multiple tracks electrochemical workstation are known.Each working electrode for being related in this case microfluidic chip structure and , can be respectively via corresponding special the corresponding interface got lines crossed with the multiple tracks electrochemical workstation to electrode and reference electrode etc. Coupled.It is described that special to get lines crossed be for each the corresponding interface of each electrode and the multiple tracks electrochemical workstation is carried out into phase The private cable being mutually coupled with.The micro-fluidic chip in this case device, its structure can also include micro-valve, the number of the micro-valve Amount is not limited, according to actual needs, and the micro-valve can be installed in any required position installed in the microfluidic chip structure; The word of micro-valve one is for the professional of micro fluidic chip technical field, and the art-recognized meanings of itself are known;The micro-valve The manufacturing technology of itself and the use of technology is also known;The component that the micro-valve is not required.
The diameter of the working electrode can allow to be that any setting is easily installed the suitable diameter used, it is however recommended to Or say preferred its scope of the diameter between 0.1 micron to 2000 microns;The length of the working electrode can permit Permitted to be that any setting is easily installed the length used, it is however recommended to or to say preferred its scope of the length be at 1 micron To between 15000 microns.
The gold size for being installed in the working electrode surface layer by spraying or point sample instrument point sample or the coating of other appropriate process is quick Feel film, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness, still, push away Preferred thickness is between 10 nanometers and 200 nanometers in other words for the thickness recommended.
The cover plate in chip structure, its material can allow to be any electrical insulating property material, for example:Polypropylene, glass Glass, polymethyl methacrylate, dimethyl silicone polymer, etc., in order to make smaller size of micro-fluidic chip, such as do Realized into the micro-fluidic chip of only 2.0 centimetres to 3.0 centimetres of super-small of length, and in the extremely short distance to ultrasonic wave Extremely fast decay, can preferably dimethyl silicone polymer be used as cover plate.Certainly, selected on large-sized micro-fluidic chip It is used as the cover plate using dimethyl silicone polymer, is also that this case technical scheme is allowed.
Positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal this is remaining Air line distance between one liquid pool can be arbitrarily selected suitable distance as needed, and still, the preferred value of the distance is Between 3 centimetres and 7 centimetres.
Described its thickness of cover plate and substrate can allow be any setting be easy to assembling thickness, the thickness of recommendation or say preferably Thickness be between 1.0 millimeters and 5.0 millimeters.Less thickness is conducive to saving material.
Described its size of ultrasonic wave damper is not limited, and described its length of ultrasonic wave damper, width, thickness may each be basis Need the arbitrary size of setting.
It is known in field of rubber technology only for the word of microcellular rubber one art-recognized meanings of itself.
The microcellular rubber is commercially available.
It is known in field of rubber technology only for the word of sponge rubber one art-recognized meanings of itself.
The sponge rubber is commercially available.
It is known in technical field of macromolecules only for the word of microporous polyurethane elastomer one art-recognized meanings of itself.
The polyurethane micropore elastomer material is commercially available.
The microcellular rubber preferred microporous silicon rubber or micropore fluorubber.
It is known in field of rubber technology only for the word of micropore silicon rubber one art-recognized meanings of itself.
The microporous silicon Rubber market is on sale.
It is known in field of rubber technology only for the word of micropore fluorubber one art-recognized meanings of itself.
The micropore fluorubber is commercially available.
The word of elastic clip one art-recognized meanings of itself are known.
The elastic clip is commercially available.
The application method of this case micro-fluidic chip:
Proposed first based on this case and the first public New stream driving principle, its application running of this case micro-fluidic chip In, the New stream driving method is determined completely without involving any additional Micropump.
The interfacial tension difference of this case to be formed between micro-fluidic chip two ends caused by the ultrasonic wave, drives liquid Stream flows in the capillary channel of the triple channel micro-fluidic chip, using multi-channel electrochemical analyzer device respectively to three kinds of hypotypes Swine flu diagnostic antigen is detected.
Corresponding three kinds of hypotypes swine flu antibody is detected with three kinds of hypotype swine flu antigens, with three kinds of hypotype swine flu antibody come Corresponding three kinds of hypotypes swine flu antigen is detected, similarly, corresponding hypotype swine flu can be diagnosed;The principle of its foundation It is necessarily antigen, antibody and to be deposited in hypotype swine flu patient, and mutually Reversible binding, reversible conjugate is formed, because This, antibody is detected with antigen and corresponding hypotype swine flu is thereby diagnosed, with gone with antibody detecting antigen and diagnosis it is corresponding Asia Type swine flu, can reach diagnostic purpose.Certainly, its corresponding electrode sensitive decorative layer of different means is not technically It is identical.
The specific detection of this case micro-fluidic chip is as follows using step:
1st, blood serum sample liquid is added in micro-pipe road, under ultrasonic wave driving, various hypotype swine flu antibody molecules are each In passage on electrode surface gold size sensitive membrane embed corresponding horseradish peroxidase-labeled hypotype swine flu specific antigen Capture.
2nd, the hypotype swine flu antibody in the hypotype swine flu specific antigen and blood serum sample of horseradish peroxidase-labeled is formed Immune complex.
3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, using the above-mentioned reaction of amperometric detection Caused curent change, is derived from the species and content of various analytes.
4th, result is subjected to comprehensive analysis, comprehensive diagnos is carried out to hypotype swine flu antibody.
It is an advantage of the invention that its close position positions the hinge-type fixture in the terminal of the micro-fluidic chip, with The miniature ultrasonic transducer units installed, the low-power launched using it, high-frequency band are attached in its hinge of the hinge-type fixture Ultrasonic wave so that without surface chemical modification or surface chemical modification strong hydrophobic micro-fluidic chip internal pipeline its Compatibility between tube wall and the test object aqueous solution is significantly increased, and this passes through possible there is provided a reality for test liquid stream Property;Meanwhile, using its strong absorbability to ultrasonic wave of dimethyl silicone polymer substrate, in shorter distance, also Be, from the terminal to the very short distance of only several centimeters yardsticks the sample introduction end in, reach the quick of ultrasonic intensity Successively decrease, the difference of the interfacial tension is thereby caused at the two ends of the micro-fluidic chip, and then, using between the two ends Pressure gap between its two ends for being formed of the difference of interfacial tension, driving test liquid stream is strongly hydrophobic in such a script Capillary channel in the terminal direction flow.By this case liquid stream drive scheme, entirely without must be to the polydimethylsiloxanes The substrate and its internal pipeline of alkane material carry out any surface chemical modification or chemical modification, have altogether dispensed with the surface chemistry and have repaiied The laborious procedures of decorations or chemical modification;And altogether dispense with the equipment of traditional Micropump etc;On the other hand, this is low The ultrasonic wave of power, high-frequency band, additionally it is possible to contain the large biological molecule in sample in the literalness naked polydimethylsiloxanes Absorption on its inner surface of pipeline of alkyl piece, and then contain its body phase of the dimethyl silicone polymer substrate to the large biological molecule The effect of swallowing up;The Reversible binding thing of the antigen, antibody and antigen and antibody is all to belong to described large biological molecule certainly Type;Because described suction-operated and the described effect of swallowing up effectively are contained that therefore, dependence test result will more Actual conditions can objectively be reflected;The effect of the low-power, high-frequency band ultrasonic wave, also includes facilitating antigen, antibody certainly Between Reversible binding reaction quick reaching, this causes dependence test operation can be to be completed than faster speed.
Due to the surface chemical modification for the dimethyl silicone polymer substrate its relevant surfaces or chemical modification behaviour need not be carried out Make, therefore, this surface chemical modification layer or chemically modified layer not need to exist, then, the dimethyl silicone polymer Its body phase interior polymer molecule of substrate constantly diffuses to the surface automatically, migrate caused by it to surface chemical modification layer or The damaging influence of chemically modified layer is also just not present.
This case its installation position is located at the ultrasonic wave damper at the sample introduction end, from its terminal of this case micro-fluidic chip to Said on the sport technique segment that ultrasonic intensity rapid decrement is realized in the such short distance in sample introduction end, its effect of the ultrasonic wave damper is suitable In the size expansion device of micro-fluidic chip, in other words, the ultrasonic wave damper its function as and significantly extend miniflow Its terminal of chip is controlled the distance between to sample introduction end, is the equal of from several centimetres of extension of script to more than ten centimetres of length Or twenties centimetres of length or longer length, so so that described terminal to the ultrasonic wave between sample introduction end in short distance The sport technique segment of intensity rapid decrement can relatively easily be reached, also, the size expansion device namely the ultrasonic wave damper Its installation and removal is all very convenient, it is important that it can also be reused.
The technical scheme of this case has dissolved its application related one to dimethyl silicone polymer substrate addressed above totally Row technical barrier.Based on this case scheme, this kind very cheap polydimethyl siloxane material is just possible in the micro-fluidic chip Prepare, production, using etc. field play bigger effect.
The miniature ultrasonic transducer units have been installed in fixation in the hinge-type fixture its hinge in this case structure, and the structure is provided One facilitates the function that the device is disassembled, in this way, the hinge-type fixture is together with appended miniature ultrasonic transducer units in its hinge Just easily it can be mutually disengaged with the micro-fluidic chip, then, the component that the part can freely depart from just can circulate benignly ground Reuse many times;The architectural feature is conducive to saving 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 depression angle of this structure Under chip internal pipeline and each electrode and each related liquid pool structural form, do not depict in the figure hinge-type fixture with And its miniature ultrasonic transducer units set up in hinge and other annexes.
Fig. 2 is its rough outside side view of this case device.
In figure, 1,2,8 be the different liquid pool of three installation positions respectively, and 3 be manifold shape turnout, and 4,9,12 are respectively Installation position is different but three laterals parallel with one another for forming UNICOM's structure in parallel, and 5 be its that be installed in lateral 4 Specific antigenic substance in the sensitive membrane structure of top layer gold size is hypotype swine flu specific antigen H1N1Working electrode, 10 are The specific antigenic substance being installed in the sensitive membrane structure of its top layer gold size in lateral 9 is anti-for hypotype swine flu specificity Former H3N2Working electrode, 11 be the specific antigen thing in the sensitive membrane structure of its top layer gold size being installed in lateral 12 Matter is hypotype swine flu specific antigen H1N2Working electrode, 6 be that, to electrode, 7 be reference electrode, and 13 be hinge-type fixture, 14 sign linkwork positions, 15 be fastening screw, and 16 be higher-order of oscillation electric signal transmission cable, and 17 be miniature super Acoustic wave transducer, 18,23 be two different hinges of locations of structures respectively, and 19 be cover plate, and 20 be substrate, and 21 be sample introduction End, 22 be terminal, and 24 be nut;The hinge-type clamp structure in legend is only the legend structure of signal, the actual hinge Its structure of formula fixture is not limited to the legend hinge-type clamp structure;Arrow in legend indicate the micro-fluidic chip its in reality During operation, driven by pressure at two ends difference, the flow direction of its test liquid stream.
The ultrasonic wave damper is depicted without in legend;Also the elastic clip is depicted without in legend.
Embodiment
In this case that Fig. 1 and Fig. 2 are shown embodiment, the structure of the device includes multichannel micro-fluidic chip, and this is micro- The structure of fluidic chip includes the substrate 20 and cover plate 19 of installing bonded to each other together, and the substrate 20 and cover plate 19 are Contain what is formed via mould pressing process or etching technics in plate object or tablet, that face towards the cover plate 19 of the substrate 20 Channel structure, the substrate 20 also containing be connected with the channel structure and pierce the substrate 20 via mould pressing process, etch work Skill or the window structure of simple drilling technology formation, substrate 20 bonded to each other being installed together are built jointly with the cover plate 19 Into the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the locations of structures of the pipeline is located at the substrate 20 are blocked and opposite side opening with the cover plate 19 interface zone bonded to each other, its side of the window by the cover plate 19, the window Mouthful locations of structures be exactly the liquid pool locations of structures, the quantity of the liquid pool is three, three liquid pools be respectively liquid pool 1, Liquid pool 2, liquid pool 8, two liquid pools therein are liquid pool 1 and its locations of structures of liquid pool 2 positioned at the sample introduction end of the micro-fluidic chip 21, a remaining liquid pool is that liquid pool 8 its locations of structures is located at when the actual sample introduction of the micro-fluidic chip is tested liquid flow in its chip Dynamic terminal 22, the terminal 22 is located remotely from each other with the sample introduction end 21, and one end of the pipeline is bonded to each other via this is similarly positioned in The manifold shape turnout 3 of interface zone be liquid pool 1 and the UNICOM of liquid pool 2 with two liquid pools positioned at sample introduction end 21 respectively, should A remaining liquid pool for the terminal 22 of the other end of pipeline with being located at the micro-fluidic chip is the UNICOM of liquid pool 8, and, The working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode 6 and reference electrode 7, the work electricity Pole is by conductive electrode and the gold size sensitive membrane for having embedded hypotype swine flu specific antigen being attached on the conductive electrode Constitute, the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of three lateral parallel connections, the work The quantity for making electrode is three, and the installation position of three working electrodes is located in three laterals respectively, and, should Specific antigen in three sensitive membrane structures of its top layer gold size of working electrode is respectively can specificity knot to hypotype swine flu antibody The three kinds of hypotype swine flu antigenic substances closed, three kinds of antigenic substances are hypotype swine flu specific antigen H respectively1N1、H3N2And H1N2, for specific expansion, 5 be the specific antigen thing in the sensitive membrane structure of its top layer gold size being installed in lateral 4 Matter is hypotype swine flu specific antigen H1N1Working electrode, 10 be that its top layer gold size being installed in lateral 9 is sensitive Specific antigenic substance in membrane structure is hypotype swine flu specific antigen H3N2Working electrode, 11 be to be installed in branched pipe The specific antigenic substance in the sensitive membrane structure of its top layer gold size in road 12 is hypotype swine flu specific antigen H1N2Work Electrode, its material of the working electrode is gold material or thermal decomposition conducting polymer material, and its pattern of the working electrode is presented Sheet is thread, and emphasis is, its material of the substrate 20 is dimethyl silicone polymer material, and its surface of substrate 20 is primary The surface of form, the surface of the primary form its be intended to refer to by any surface chemical modification or any surface chemistry not change Property the material primary form surface, the structure of the device also includes hinge-type fixture 13, and the hinge-type fixture 13 is outside it Shape profile is similar to hinge, and the hinge-type fixture 13 is by two hinges 18,23 for being mutually hinged and through this two One fastening screw 15 of hinge 18,23 and one match with the fastening screw 15 and are socketed in the fastening screw 15 The nut 24 for being used for fastening and hand break loose manually together is constituted, and the nut 24 in legend is a kind of butterfly nut, should Kind butterfly nut is relatively convenient in practical operation, and two hinges 18,23 of the hinge-type fixture 13 are respectively mutually leaned on its tip Hold together and clamp the micro-fluidic chip, the tip is positioned in the locations of structures of the neighbouring terminal 22 of the micro-fluidic chip, A hinge at least in is to attach fixation in hinge 18 or hinge 23 to be equiped with miniature ultrasonic transducer units 17, In this example, the miniature ultrasonic transducer units 17 are to attach to be installed in hinge 18, and, higher-order of oscillation electric signal transmission electricity Cable 16, one end of the higher-order of oscillation electric signal transmission cable 16 links together with the miniature ultrasonic transducer units 17;The conjunction Page fixture 13 facilitates the function that the device is disassembled there is provided one;Its major function of the miniature ultrasonic transducer units 17 be During the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it is reduced between sample solution and the inwall of the pipeline Interfacial tension, can be compatible, also, utilize the sample introduction end 21 and the terminal 22 and the miniature ultrasonic Difference in the distance between the installation position of transducer 17 difference and its ultrasonic intensity experienced, described in induced synthesis Between difference between its interfacial tension of sample introduction end 21 and the terminal 22 its interfacial tension, the micro-fluidic chip two ends Interfacial tension difference can form pressure gap between the two ends of the micro-fluidic chip, the pressure gap can drive sample solution to The terminal 22 flows;Its function of the miniature ultrasonic transducer units 17 also includes checking in sample with its ultrasonic wave launched Its absorption on the inner surface of pipeline of contained large biological molecule, and then check the substrate of the dimethyl silicone polymer material Swallow up effect of 20 its body phase to the large biological molecule;Its function of the substrate 20 of the dimethyl silicone polymer material includes and lid Piece 19 and working electrode 5,10,11 and the micro-fluidic chip is together built to electrode 6 and reference electrode 7, it is soft simultaneously to have bullet Property the substrate 20 of the dimethyl silicone polymer material its function also include with its property to the strong absorption of ultrasonic wave, to ultrasound Ripple is absorbed strongly, and the limited short distance thereby arrived between the sample introduction end 21 in the micro-fluidic chip terminal 22 it Inside realize the rapid decrement of ultrasonic intensity;And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular Or it is 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, and the medial surface of each clamping limb is relative with the medial surface of another clamping limb, one of clamping The medial surface of arm is close to the sample introduction end 21 of the micro-fluidic chip, and the medial surface of another clamping limb is close to ultrasonic wave abatement Device, the elastic clip with its gripping strength by the sample introduction end 21 of the micro-fluidic chip and the ultrasonic wave damper it is bonded to each other be clipped in Together, the strong consumption to ultrasonic wave that the ultrasonic wave damper is brought with its material, is further supported micro-fluidic at this The chip terminal 22 to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 21, and by This further expands the difference between described its interfacial tension of sample introduction end 21 and the terminal 22 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, its test liquid The flow direction of stream.
The miniature ultrasonic transducer units 17 set up in the hinge-type fixture 13 and one hinge are depicted without in Fig. 1 And higher-order of oscillation electric signal transmission cable 16;Also, the higher-order of oscillation electric signal hair is depicted without in Fig. 1 and Fig. 2 The raw associate member such as device and multiple tracks electrochemical workstation.
Involved miniature ultrasonic transducer units 17 are commercially available;It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal transmission cable 16 is commercially available;It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available;It can also be customized to relevant manufacturers.
Each working electrode in this example structure and electrode and reference electrode via each special cable or can be said respectively Get lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as annex or saying interface connection of getting lines crossed.
Involved hinge-type fixture 13 itself can be carried out simple cutting using commercially available hinge and be changed a social system.Hinge-type folder in legend The structural form of tool 13 is only an example, and the structural form of this case hinge-type fixture is not limited to the structural form in the legend.
Capillary on usual expression and significance refers to hydrophilic capillary glass tube;Capillary channel involved by this case is hydrophobic Capillary form pipeline.

Claims (10)

  1. The hydrophobic PDMS of the last 1. is as the hypotype swine flu detection chip apparatus of substrate material, and it is micro- that the structure of the device includes multichannel Fluidic chip, the structure of the micro-fluidic chip includes the substrate and cover plate of installing bonded to each other together, and the substrate and cover plate are equal For plate object or tablet, the conduit via mould pressing process or etching technics formation is contained in 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 of hole technique formation, substrate bonded to each other being installed together has been built into jointly with the cover plate contains pipeline configuration And the micro-fluidic chip for the liquid pool structure being attached thereto, the locations of structures of the pipeline is located at the substrate and the cover plate is bonded to each other Interface zone, its side of the window is blocked by the cover plate and opposite side is opened, and the locations of structures of the window is exactly the knot of the liquid pool Structure position, the quantity of the liquid pool is three, and its locations of structures of two liquid pools therein is located at the sample introduction end of the micro-fluidic chip, Its locations of structures of a remaining liquid pool is located at the terminal of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, should Terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is via the manifold shape turnout for being similarly positioned in the interface zone bonded to each other Respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline should with the terminal positioned at the micro-fluidic chip A remaining liquid pool UNICOM, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode with And reference electrode, the working electrode by conductive electrode and be attached on the conductive electrode to have embedded hypotype swine flu special The gold size sensitive membrane of Specific Antigen is constituted, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by three branches Pipeline parallel connection is constituted, and the quantity of the working electrode is three, and the installation position of three working electrodes is located at described three respectively In lateral, and, the specific antigen in the sensitive membrane structure of its top layer gold size of three working electrodes is to hypotype pig respectively Three kinds of hypotype swine flu antigenic substances that influenza antibodies can be specifically bound, three kinds of antigenic substances are that hypotype swine flu is special respectively Property antigen H1N1、H3N2And H1N2, its material of the working electrode is gold material or thermal decomposition conducting polymer material, the work Make electrode its pattern presentation sheet or thread, it is characterised in that its material of the substrate is dimethyl silicone polymer material, the substrate Its surface is the surface of primary form, the surface of the primary form its be intended to refer to not by any surface chemical modification or appoint The surface of the primary form of the material of what surface chemical modification, the structure of the device also includes hinge-type fixture, hinge-type folder Has its appearance profile likeness in form hinge, the hinge-type fixture is by two hinges being mutually hinged and through two hinges One fastening screw and one match with the fastening screw and fastened manually and hand with being used for of connecting together of the fastening screw The dynamic nut released is constituted, and two hinges of the hinge-type fixture are respectively mutually drawn close with its tip and clamp the micro-fluidic chip, institute State tip to be positioned in the locations of structures of the neighbouring terminal of the micro-fluidic chip, pasted in a hinge at least in Attached fixation is equiped with miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, higher-order of oscillation electric signal transmission One end of cable links together with the miniature ultrasonic transducer units;The hinge-type fixture facilitates what the device was disassembled there is provided one Function;Its major function of the miniature ultrasonic transducer units is, in the actual sample introduction test of micro-fluidic chip, to utilize surpassing that it is launched Sound wave reduces the interfacial tension between sample solution and the inwall of the pipeline, can be compatible, also, enters described in The distance between sample end and the terminal and the miniature ultrasonic transducer units installation position difference and its ultrasound experienced Difference between difference in intensity of wave, 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 two ends can form pressure gap between the two ends of the micro-fluidic chip, the pressure Difference can drive sample solution to the end flow;Its function of the miniature ultrasonic transducer units also includes the ultrasound launched with it Ripple checks in sample contained large biological molecule its absorption on the inner surface of pipeline, and then checks the polydimethylsiloxanes Swallow up effect of its body phase of the substrate of alkane material to the large biological molecule;Its function bag of the substrate of the dimethyl silicone polymer material Include with cover plate and working electrode and the micro-fluidic chip is together built to electrode and reference electrode, the poly- diformazan that is soft and having elasticity The substrate of radical siloxane material its function also includes, with its property to the strong absorption of ultrasonic wave, ultrasonic wave being absorbed strongly, And thereby realize the quick of ultrasonic intensity within micro-fluidic chip terminal to the limited short distance between the sample introduction end Successively decrease;And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped;The ultrasonic wave damper Its material 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, and the medial surface of one of clamping limb is close to the miniflow The sample introduction end of chip is controlled, the medial surface of another clamping limb is close to the ultrasonic wave damper, and the elastic clip will with its gripping strength The sample introduction end of the micro-fluidic chip and the ultrasonic wave damper are clipped together bonded to each otherly, and the ultrasonic wave damper is with its material institute The strong consumption to ultrasonic wave brought, is further supported in the micro-fluidic chip terminal to limited between the sample introduction end Short distance within realize the rapid decrement of ultrasonic intensity, and thereby further expand described its interfacial tension of sample introduction end with it is described Difference between its interfacial tension of terminal.
  2. 2. strong hydrophobic PDMS according to claim 1 is as the hypotype swine flu detection chip apparatus of substrate material, it is special Levy and be, the pipeline and the lateral and the manifold shape turnout are capillary channel.
  3. 3. strong hydrophobic PDMS according to claim 1 is as the hypotype swine flu detection chip apparatus of substrate material, it is special Levy and be, the thermal decomposition conducting polymer be by polyimides or polyacrylonitrile be heat-treated through anoxybiotic after the electric conductivity material that is formed Material.
  4. 4. strong hydrophobic PDMS according to claim 1 is as the hypotype swine flu detection chip apparatus of substrate material, it is special Levy and be, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the working electrode Length between 1 micron to 15000 microns.
  5. 5. strong hydrophobic PDMS according to claim 1 is as the hypotype swine flu detection chip apparatus of substrate material, it is special Levy and be, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
  6. 6. strong hydrophobic PDMS according to claim 1 is as the hypotype swine flu detection chip apparatus of substrate material, it is special Levy and be, its material of the cover plate in structure is dimethyl silicone polymer material.
  7. 7. strong hydrophobic PDMS according to claim 1 is as the hypotype swine flu detection chip apparatus of substrate material, it is special Levy and be, positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with the remainder positioned at the micro-fluidic chip terminal A liquid pool between air line distance between 3 centimetres and 7 centimetres;The cover plate in structure and substrate its thickness are situated between Between 1.0 millimeters and 5.0 millimeters.
  8. 8. strong hydrophobic PDMS according to claim 1 is as the hypotype swine flu detection chip apparatus of substrate material, it is special Levy and be, the microcellular rubber is micropore silicon rubber or micropore fluorubber.
  9. 9. strong hydrophobic PDMS according to claim 1 is as the hypotype swine flu detection chip apparatus of substrate material, it is special Levy and be, the structure of the device also includes higher-order of oscillation electric signal generator, its is another for the higher-order of oscillation electric signal transmission cable End is connected with the higher-order of oscillation electric signal generator.
  10. 10. strong hydrophobic PDMS according to claim 1 is as the hypotype swine flu detection chip apparatus of substrate material, its It is characterised by, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 5 milliwatts and 9000 milliwatts, and this is micro- The frequency of its ultrasonic wave operationally launched of type ultrasonic transducer is between 100KHz and 12MHz.
CN201610100297.8A 2016-02-15 2016-02-15 Strong hydrophobic PDMS as substrate material hypotype swine flu detection chip apparatus Withdrawn CN107085101A (en)

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