CN107649191A - 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 PDF

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CN107649191A
CN107649191A CN201610626770.6A CN201610626770A CN107649191A CN 107649191 A CN107649191 A CN 107649191A CN 201610626770 A CN201610626770 A CN 201610626770A CN 107649191 A CN107649191 A CN 107649191A
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micro
substrate
cholera
fluidic chip
terminal
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洪小女
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    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
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    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
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Abstract

The present invention relates to a kind of special cheap cholera diagnosis micro fluidic device of sap flow process mode, belong to analysis testing field.Serial problem be present if for making the substrate of cholera diagnosis micro-fluidic chip in dimethyl silicone polymer i.e. PDMS that is cheap and easily processing；Its surface of the PDMS material is strongly hydrophobic, and targetedly surface is modified or surface modification, its effect are difficult to persistently, and this case aims to solve the problem that the serial relevant issues.This case main points are, the selected PDMS with ecosystem surface of substrate, and its neighbor positions attaches installing miniature ultrasonic transducer units in the sample liquid stream terminal of the micro-fluidic chip, interfacial tension is reduced with ultrasonic wave, strong absorbability using PDMS to ultrasonic wave simultaneously, reach ultrasonic intensity rapid decrement in short distance, and thus form interfacial tension difference at the both ends of the chip, the interfacial tension difference causes the both ends to form pressure differential, and the pressure differential drives sample liquid stream to be flowed along capillary channel to the terminal direction.

Description

The special cheap cholera diagnosis micro fluidic device of sap flow process mode
Technical field
The present invention relates to a kind of special cheap cholera diagnosis micro fluidic device of sap flow process mode, belongs to analysis and surveys Examination field.
Background technology
The micro-fluidic cholera diagnostic techniques background of associated multi-channel, may refer to the patents of invention such as CN 200910150930.4 Application case.
Only for the microflow control technique overall general picture of itself, famous micro-fluidic expert Mr. Lin Ping Cheng may refer to not The monograph " diagram Microfluid based Lab on a chip " gone out before long, the monograph is published via Science Press, and the monograph is to micro-fluidic Past of technology, now, and, vision of the future etc. 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 be etched with the substrate of small fluid course and fit together therewith Cover plate, the small fluid course on the substrate, before upper cover plate is assembled, it is apparent on see to be exactly some micro-channels, to wait until After covering cover plate thereon, just really closure forms the small fluid course, the conduit inner surface of the micro-channel together with The part cover plate that surround the micro-channel forms described small fluid course together；So, it is clear that after assembling completes The small fluid course, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, should The state or property of micro-channel inner surface substantially determine the integrality or property of the small fluid course；Therefore say, this The inner surface state or inner surface property of micro-channel of the individual structure on substrate are key factors；In principle, it is any can The material of its solid forms is kept or kept substantially, can be used to make substrate and cover plate, such as, it can act as substrate and lid The material of piece can be monocrystalline silicon piece, quartz plate, sheet glass, high polymer for example dimethyl silicone polymer, polymethyl methacrylate, Makrolon etc.；Certainly, the selection of substrate and the selection of cover plate be able to can also be differed with identical；From material consumption, make From the point of view of difficulty and application popularization prospect etc. etc., not small difference, the especially choosing of that substrate between these materials be present Material, have a great influence.
In various substrate making materials, dimethyl silicone polymer, i.e. PDMS, comparatively very easily shaping, at this It is extremely simple that micro-channel is made on the substrate of sample, and the lower cost for material, base is made with the polydimethyl siloxane material Piece, micro-channel, and the cover plate phase made with the cheap material such as glass or polypropylene or other plastic sheets are being suppressed or etched thereon Coordinate, be a kind of more satisfactory selection seemingly；Certainly, patch material can also select to use cheap dimethyl silicone polymer Material：So, this substrate selection is the scheme of polydimethyl siloxane material, and material is extremely cheap, and making is extremely simple, seems It should be extremely easy to popularize, promote.
But thing is really not so simple.
First, this polydimethyl siloxane material, that is, the material that alphabetical PDMS is referred to of abridging, itself are a kind of strong Strong hydrophobic material, micro-channel is built on this material, if without being operated for the modified of the micro-channel surface, that , after overall assembling is completed, that is, after covering cover plate, because the micro-channel its inner surface in structure occupies most liquid The inner surface of circulation road, then, its strong hydrophobic property of the PDMS micro-channels inner surface, is deciding factor, it can cause Similar to the aqueous solution the fine liquid stream of polar liquid by becoming very difficult, its flow resistance is big, or even in general is micro- Pump is all difficult to promote, certainly, if cover plate also selects to use the PDMS material, then, problem is substantially identical, similar； Therefore, among prior art, modification is modified particular for the micro-channel inner surface on the PDMS material, is necessary behaviour Make；So, this is pretty troublesome for the modified operation of PDMS micro-channel inner surfacesThat falls nor this problem, is formed tight Weight technology puzzlement, be another problem：PDMS polymer molecules inside its body phase of this PDMS material substrate have automatic The characteristic diffuse to the surface, migrated, the spy that this substrate body phase inside PDMS polymer molecules are diffused to the surface, migrated automatically Property, the state after modification by its inner surface of that micro-channel of surface modifying and decorating will be caused can not to maintain long enough Time, the holding time for micro-channel its inner surface state after that is surface-modified be substantially only sufficient to complete laboratory internal The time of test experiments needs；In other words, by surface modification or the PDMS micro-channel inner surfaces of surface modification, it is modified The surface state that is formed can not be lasting afterwards or after saying modification, but soon automatically tends to or say and become surface modification again Surface state before, the strong hydrophobic surface state of that script is returned in the shorter time, then, just think, this The micro-fluidic chip of sample can largely make, mass storage, be widely popularized, and answer is it is obvious that is, impossible.This Micro-channel on PDMS material, if not doing surface modification, similar to the aqueous solution the fine liquid stream of polar solvent can not pump it is logical Cross, chip also cannot just use；And if having done surface modification, its state after modifying can not be persistently kept again, or together Sample can not popularization and application.
So, how to accomplish that substrate can either be made using cheap PDMS material, and the microflute can be released Road inner surface decorating state can not persistently, chip can not largely make, largely lay in and then be widely popularized and such a make ability The puzzlement that the numerous professionals in domain are entangled with for a long time, the highly difficult problem that exactly one its obvious technology barrier can not despise.
Be present many year in the highly difficult problem, so far, not yet properly settled.
Second, the PDMS material of non-surface modification, it is stated that, its surface is strongly hydrophobic above, this strong hydrophobic Material surface and also have another problem, that is, this strong hydrophobic PDMS surfaces can adsorb large biological molecule, and And these adsorbed large biological molecules can also further depression further on PDMS surfaces, gradually fall into it is gradually deep, until It is heavy to be trapped within the body phase of PDMS substrates, in fact, this process, partly it is also due to PDMS material body phase interior polymer Molecule, which has, to be diffused to the surface, caused by travel motion；Such case, it can also be explained from another angle, i.e. continue not Disconnectedly from inside PDMS body phases to those polymer molecules of its diffusion into the surface, migration, its result moved, be little by little by that It has been involved in a bit by the large biological molecule of adsorption within the body phase of PDMS substrates, briefly, these adsorbed biologies Macromolecular is exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up the phenomenon of large biological molecule, its institute Caused by influence, necessarily cause the severe deviations of all kinds of test data of experiment for being related to large biological molecule.
As described above, the problem of PDMS substrates, is, its not only adsorption large biological molecule, and swallow up biological big point Son, so, as the large biological molecule of experiment test object, its disappearance will not stop because surface saturation is adsorbed, and It is, it is constantly adsorbed, also constantly swallowed up.
On PDMS substrates, its body phase is constantly swallowed up and tests showing for associated biomolecule macromolecular in related experiment test process As, it is to say that another kind, which is explained, substantial amounts of Minute pores in PDMS body phases be present, associated biomolecule macromolecular by after adsorption, Depression enters these Minute pores, and then is swallowed up；However, inventor thinks, those can allow the sky of miniature scale Qi leel squeezes into the Minute pores therebetween, not equal to saying that they also can directly allow the large biological molecule of relative large scale to enter Enter, both difference on yardstick are huge, must not make sweeping generalizations.Explanation is bypassed, in any case, as dependence test analysis object Large biological molecule is adsorbed by PDMS substrate micro-channels inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is person in charge of reception at ceremonies Phenomenon existing for sight.
, can be from containment PDMS surfaces pair in order to prevent swallow up effect of this PDMS substrate bodies relative to large biological molecule The absorption of large biological molecule addresses, and method is chemically modified modification aiming at the PDMS material surface, for For PDMS is the situation of substrate material, modification exactly is chemically modified to the surface of described micro-channel part, by changing The micro-channel inner surface of modification is learned, its absorption to large biological molecule can be contained, and then avoid large biological molecule Swallowed up by PDMS substrate body phases；But or that old problem, that is, the chemical modification on PDMS material surface is modified Surface state afterwards can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface, move automatically The process of shifting, it soon can become that micro-channel inner surface state being modified by surface chemical modification again script strong and dredge Water and the state of strong adsorption large biological molecule, in other words, no matter how professionals in the field turn from side to side, the PDMS bases Its micro-channel inner surface of piece is always rapidly to strong hydrophobic surface state evolution.
So, how can either obtain that PDMS material price is extremely cheap, substrate makes extremely easy benefit, and can is enough Reach and contain the absorption process of the PDMS substrate micro-channel inner surfaces to large biological molecule for a long time, and then prevent PDMS substrate body phases The effect of swallowing up to large biological molecule so that related chip manufactured goods be able to maintain that one it is prolonged enough, reasonably guarantee the quality Phase, it is exactly a very intractable problem.The problem equally makes this area numerous as another problem addressed above Professional is entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise. Also be present many year in the problem, so far, also not yet properly settled.
The content of the invention
The technical problem to be solved by the invention is to provide a package solution, solves totally above Two problems addressed, also, the solution is applied to cholera diagnosis multichannel micro-fluidic chip field, formed a kind of Multichannel micro-fluidic device is used in new cholera diagnosis.
The present invention solves the technical problem by following scheme, and the device that the program provides is a kind of sap flow process mode Special cheap cholera diagnosis micro fluidic device, the structure of the micro fluidic device include multichannel micro-fluidic chip, and this is micro- The structure of fluidic chip includes being bonded to each other the substrate and cover plate of installing together, and the substrate and cover plate are plate object or piece The channel structure via mould pressing process or etching technics formation, the base are contained in shape thing, that face towards the cover plate of the substrate Piece also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or simple drilling technology shape Into window structure, be bonded to each other the substrate that is installed together and the cover plate be built into jointly containing pipeline configuration and with Connected liquid pool structure micro-fluidic chip, the locations of structures of the pipeline be located at the interface that the substrate and the cover plate are bonded to each other Region, its side of the window is blocked by the cover plate and opposite side opens, and the locations of structures of the window is exactly the structure of the liquid pool 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, remaining Under the liquid flowing in its chip when being located at the actual sample introduction test of the micro-fluidic chip of liquid pool its locations of structures terminal, should Terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is branched off via the manifold shape for being similarly positioned in the interface zone being bonded to each other Road respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline with positioned at the micro-fluidic chip the terminal A remaining liquid pool UNICOM, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and right Electrode and reference electrode, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded cholera The gold size sensitive membrane of specific antigen is formed, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by four Lateral is in parallel to be formed, and the quantity of the working electrode is four, and the installation position of four working electrodes is located at institute respectively State in four laterals, and, the specific antigen in its top layer gold size sensitivity membrane structure of four working electrodes is respectively The four kinds of cholera antigenic substances that can be specifically bound to cholera antibody, four kinds of antigenic substances be cholera TP0821 antigens respectively with And cholera TP0319 antigens and cholera TP0624 antigens and cholera O139 antigens, its material of the working electrode are gold materials Sheet or thread is presented in matter or thermal decomposition conducting polymer material, its pattern of the working electrode, and emphasis is its material of the substrate Dimethyl silicone polymer material, its surface of the substrate is the surface of primary form, the surface of the primary form its be meant to It is that this is micro-fluidic not by any surface chemical modification or the surface of the primary form of the material of any surface chemical modification The structure of device also includes miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, the higher-order of oscillation electric signal One end of transmission cable links together with the miniature ultrasonic transducer units, and the miniature ultrasonic transducer units are installed in this with attaching The position of the cover plate of micro-fluidic chip or the neighbouring terminal of substrate；Its major function of the miniature ultrasonic transducer units is micro- During the test of fluidic chip actual sample introduction, the ultrasonic wave launched using it is reduced between sample solution and the inwall of the pipeline Interfacial tension, can be compatible, also, filled using the sample introduction end and the terminal and the miniature ultrasonic transducer units If the difference on the distance between position difference and its ultrasonic intensity experienced, its boundary of sample introduction end described in induced synthesis Difference between face tension force and the terminal its interfacial tension, interfacial tension difference between the micro-fluidic chip both ends can be Pressure gap is formed between the both ends of the micro-fluidic chip, the pressure gap can drive sample solution to the end flow； The ultrasonic wave that its function of the miniature ultrasonic transducer units also includes being launched with it checks large biological molecule contained in sample Its absorption on the inner surface of pipeline, and then it is big to the biology to check its body phase of the substrate of the dimethyl silicone polymer material The effect of swallowing up of molecule；Its function of the substrate of the dimethyl silicone polymer material is included with cover plate and working electrode and to electrode It is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and reference electrode together builds the micro-fluidic chip Also include with its property to the strong absorption of ultrasonic wave, ultrasonic wave is absorbed strongly, and thereby should in the micro-fluidic chip Terminal is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end, and its locations of structures was positioned at should A remaining liquid pool for the terminal of liquid flowing is also referred to as terminal liquid in its chip when the actual sample introduction of micro-fluidic chip is tested Pond, some high hydroscopic resin particles are filled with the terminal liquid pool, its opening end of the terminal liquid pool is covered by breathable microporous film.
The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and cholera specific antigen solution uniformly, is used a little Sample instrument point sample is coated on specified structure position, and forms its drying and forming-film.Cholera specificity in the gold size sensitive membrane Antigen is the cholera antigen of horseradish peroxidase or glucose oxidase mark, and the gold size sensitive membrane has been included as solid Determine above-mentioned each cholera specific antigen and introduce complementary medium therein, the complementary medium such as chitosan, acetic acid are fine Dimension is plain, gelatin is therein a kind of or their mixture.
The pipeline and the lateral and the manifold shape turnout in the microfluidic chip structure, in it Footpath size may each be arbitrarily selected size, still, for as far as possible less with prepare liquid sample and reduction reagent loss etc. Consideration, the pipeline and the lateral and the manifold shape turnout preferably select capillary level passage, institute The passage for stating capillary level implies that its internal diameter passage suitable with the internal diameter of the capillary on ordinary meaning.The capillary is in it The shape of cross section of portion's passage can be arbitrary shape, and the shape of cross section is for example circular, oval, square, rectangle, bar Shape, naturally it is also possible to it is the linear of bending arbitrarily be present, also, the interior shape of the capillary is with the extension of pipeline, The shape of cross section of different parts can also allow to be different shapes.Only for the word of capillary one, its art-recognized meanings is public Know.
What is be related in structure is the electrode of microsize to electrode and reference electrode, and its electrode shape, which may each be, appoints The selected shape of meaning, the arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..It is described Art-recognized meanings to electrode and the reference electrode vocabulary of itself are known.
It is related to several liquid pools in this case microfluidic chip structure, the liquid pool is the pond shape or capsule for transitional liquid storage Shape constructs, and its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, and the cavity shape is for example round Cylindrical cavity shape, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..The size of the liquid pool can be any Selected size, still, in order to as far as possible less with prepare liquid sample and reduce reagent loss, the liquid pool be preferably capable of with The liquid pool of the microminiature of capillary matching.
Only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field, It is known.
Various sizes, variously-shaped ultrasonic transducer are commercially available；Its size of commercially available miniature ultrasonic transducer units It may diminish to the magnitude only calculated with millimeter.
Only with regard to miniature ultrasonic transducer units its technique for fixing on general industry application solid body surface its It is known general technology for the professional in ultrasonic technology field for body.This case is not to this expansion superfluous words.
Only with regard to naked PDMS substrates itself micro-channel molding or lithographic technique for, be open-and-shut known skill Art；Similarly, the technology of hole-opening is even more known simple technique on naked PDMS substrates.This case is not also superfluous to this expansion Speech.
The industrial products market of involved its all size of higher-order of oscillation electric signal transmission cable is on sale.
The structure of the micro fluidic device can also include higher-order of oscillation electric signal generator；The higher-order of oscillation electric signal passes Its other end of transmission cable can be connected with the higher-order of oscillation electric signal generator.
The involved higher-order of oscillation electric signal generator technology of itself, come for the professional in ultrasonic technology field Say, be simple and known；The higher-order of oscillation electric signal generator can customize to ultrasonic instrument specialized factory.
The preferred scope of its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 2 milliwatts and 2000 milliwatts Between；The preferred scope of the frequency of its ultrasonic wave operationally launched of the miniature ultrasonic transducer units be between 100KHz with Between 12MHz.
Only for the word of high hydroscopic resin one art-recognized meanings of itself, come for the professional of chemical field Say, be known.
The high hydroscopic resin is commercially available.
Only for the word of breathable microporous film one art-recognized meanings of itself, for the professional of technical field of membrane, It is known.
The breathable microporous film is commercially available.
This case device can further include some annexes certainly, and the annex is such as multiple tracks electrochemical workstation Deng the art-recognized meanings of the multiple tracks electrochemical workstation are known.The each work being related in this case microfluidic chip structure Electrode and to electrode and reference electrode etc., special it can get lines crossed and the multiple tracks electrochemical workstation via corresponding respectively The corresponding interface coupled.It is described that special to get lines crossed be for by each phase of each electrode and the multiple tracks electrochemical workstation Answer the private cable that interface is coupled to each other.The micro-fluidic chip in this case device, its structure can also include micro-valve, The quantity of the micro-valve is unlimited, and according to being actually needed, the micro-valve can be installed in any need in the microfluidic chip structure Position to be mounted；The word of micro-valve one is for the professional of micro fluidic chip technical field, the art-recognized meanings of itself It is known；The micro-valve itself manufacturing technology and the use of technology is also known；The component that the micro-valve is not required.
The diameter of the working electrode can allow to be that any setting is easily installed the suitable diameter used, still, It is recommending or say preferable its scope of the diameter between 0.1 micron to 2000 microns；The length of the working electrode can To allow to be that any setting is easily installed the length used, it is however recommended to or to say the preferable length its scope be 1 Micron is between 15000 microns.
It is installed in by spraying or point sample instrument point sample or the coating of other appropriate process described in the working electrode surface layer Gold size sensitive membrane, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness, It is however recommended to thickness preferable thickness is between 10 nanometers and 200 nanometers in other words.
The cover plate in chip structure, its material can allow to be any electrical insulating property material, such as：Polypropylene, Glass, polymethyl methacrylate, dimethyl silicone polymer, etc., in order to make smaller size of micro-fluidic chip, for example do Into the micro-fluidic chip of only 2.0 centimetres to 3.0 centimetres of super-small of length, and realized in the extremely short distance to ultrasonic wave Extremely fast decay, can preferably dimethyl silicone polymer be used as cover plate.Certainly, selected on large-sized micro-fluidic chip Using dimethyl silicone polymer it is used as the cover plate, and this case technical scheme is allowed.
Positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal should Air line distance between a remaining liquid pool can be arbitrarily selected suitable distance, still, the distance as needed Preferred value is between 3 centimetres and 7 centimetres.
Described its thickness of cover plate and substrate can allow be any setting the thickness for being easy to assembling, the thickness of recommendation or say Preferable thickness is between 1.0 millimeters and 5.0 millimeters.Less thickness is advantageous to save material.
The application method of this case micro-fluidic chip：
Itd is proposed first based on this case and the first public new liquid stream driving principle, its application of this case micro-fluidic chip are transported Among work, the new liquid stream driving method is determined completely without involving any additional Micropump.
The interfacial tension difference that this case is formed between micro-fluidic chip both ends caused by the ultrasonic wave, Driving liquid stream flows in the capillary channel of the four-way micro-fluidic chip, right respectively using four-way electrochemical analytical instrument Four kinds of cholera antibody are detected.
Corresponding four kinds of cholera antibody is detected with four kinds of cholera antigens, with detecting corresponding four with four kinds of cholera antibody Kind cholera antigen, similarly, can cholera diagnosis；The principle of its foundation is, necessarily antigen, antibody in cholera patient And deposit, and mutual Reversible binding forms reversible conjugate, therefore, antibody and thereby cholera diagnosis is detected with antigen, with Antibody goes to detect antigen and cholera diagnosis, can reach diagnostic purpose.Certainly, its corresponding electrode sensitive of different means is repaiied Adorn layer technically and differ.
The specific detection of this case micro-fluidic chip is as follows using step：
1st, blood serum sample liquid is added in micro-pipe road, under ultrasonic wave driving, various cholera antibody molecules are by each logical The cholera specific antigen for the corresponding horseradish peroxidase-labeled that gold size sensitive membrane embeds captures on electrode surface in road.
2nd, the cholera specific antigen of horseradish peroxidase-labeled is formed immune multiple with the cholera antibody in blood serum sample Compound.
3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, it is above-mentioned using amperometric detection Curent change caused by reaction, it is derived from the species and content of various analytes.
4th, result is subjected to comprehensive analysis, comprehensive diagnos is carried out to cholera antibody.
It is an advantage of the invention that its close position installs miniature ultrasonic with attaching in the terminal of the micro-fluidic chip Wave transducer, it is launched using the miniature ultrasonic transducer units low-power, the ultrasonic wave of high-frequency band so that without table Compatibility between strong hydrophobic its tube wall of micro-fluidic chip internal pipeline and the test object aqueous solution of face chemical modification It is significantly increased, this is sample liquid stream by providing a realistic possibility；Meanwhile using dimethyl silicone polymer substrate its To the strong absorbability of ultrasonic wave, in shorter distance, it is, from the terminal to the sample introduction end only In the very short distance of several centimeters of yardsticks, reach the rapid decrement of ultrasonic intensity, thereby described the two of the micro-fluidic chip The difference of the interfacial tension is caused at end, and then, utilize its both ends for being formed of the difference of the interfacial tension between the both ends Between pressure gap, driving sample liquid stream is in the strong hydrophobic capillary channel of such a script to the terminal direction Flowing.By this case liquid stream drive scheme, entirely without must enter to the substrate and its internal pipeline of the dimethyl silicone polymer material Any surface chemical modification of row or chemical modification, have altogether dispensed with the laborious procedures of the surface chemical modification or chemical modification； And the equipment of traditional Micropump etc is altogether dispensed with；On the other hand, the ultrasonic wave of the low-power, high-frequency band, It can also contain large biological molecule in sample on literalness naked its inner surface of pipeline of dimethyl silicone polymer substrate Absorption, and then contain the swallow up effect of its body phase of dimethyl silicone polymer substrate to the large biological molecule；The antigen, The Reversible binding thing of antibody and antigen and antibody is all the type for belonging to described large biological molecule certainly；Due to described suction Attached effect and the described effect of swallowing up effectively are contained that therefore, dependence test result will be better able to objectively reflect reality Border situation；The effect of the low-power, high-frequency band ultrasonic wave, also include facilitating the Reversible binding between antigen, antibody anti-certainly That answers quickly reaches, and this causes dependence test operation can be with than the completion of faster speed.
Due to surface chemical modification or chemistry for its relevant surfaces of the dimethyl silicone polymer substrate need not be carried out Modified operation, therefore, this surface chemical modification layer or chemically modified layer not need to exist, then, the poly dimethyl Its body phase interior polymer molecule of siloxanes substrate constantly diffuses to the surface automatically, migrate caused by it to the surface chemistry The damaging influence of decorative layer or chemically modified layer is also just not present.
It is related that the technical scheme of this case has dissolved its application to dimethyl silicone polymer substrate addressed above totally A series of technical barriers.Based on this case scheme, the very cheap polydimethyl siloxane material of this kind is just possible to micro- at this It is prepared by fluidic chip, production, using etc. field play bigger effect.
Brief description of the drawings
Fig. 1 is the schematic diagram of this case micro fluidic device embodiment chip part construction, it is shown that this structure Depression angle under chip internal pipeline and the structural form of each electrode and each related liquid pool, do not depict in the figure described 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, and 3 be manifold shape turnout, and 4,7,11,14 are respectively Installation position is different but four laterals parallel with one another for forming UNICOM's structure in parallel, and 5 be its that be installed in lateral 4 Specific antigenic substance in the gold size sensitivity membrane structure of top layer is the working electrode of cholera TP0821 antigens, and 6 be to be installed in branch The specific antigenic substance in its top layer gold size sensitivity membrane structure in pipeline 7 is the working electrode of cholera TP0319 antigens, 12 It is that specific antigenic substance in its top layer gold size sensitivity membrane structure being installed in lateral 11 is cholera TP0624 antigens Working electrode, 13 be specific antigenic substance in its top layer gold size sensitivity membrane structure being installed in lateral 14 for suddenly The working electrode of random O139 antigens, 8 be to electrode, and 9 be reference electrode, and 15 be the substrate of dimethyl silicone polymer material, and 16 are Cover plate, 17 be higher-order of oscillation electric signal transmission cable, and 18 be miniature ultrasonic transducer units, 19 be the micro-fluidic chip it is described enter Sample end, 20 be the terminal of the micro-fluidic chip；Arrow in legend indicate the micro-fluidic chip its in actual motion When, driven by pressure at two ends difference, the flow direction of its sample 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 core Piece, the structure of the micro-fluidic chip include being bonded to each other the substrate 15 and cover plate 16 of installing together, the substrate 15 and cover plate 16 be plate object or tablet, and that face towards the cover plate 16 of the substrate 15 is contained via mould pressing process or etching technics The channel structure of formation, the substrate 15 also containing be connected with the channel structure and pierce the substrate via mould pressing process, quarter The window structure that etching technique or simple drilling technology are formed, is bonded to each other the substrate 15 being installed together and the cover plate 16 is common Be built into the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the liquid pool be liquid pool 1, liquid pool 2, Liquid pool 10, the locations of structures of the pipeline are located at the interface zone that the substrate 15 is bonded to each other with the cover plate 16, its side of the window Blocked and opposite side opening by the cover plate 16, the locations of structures of the window is exactly the liquid pool 1, liquid pool 2, the structure bit of liquid pool 10 Put, the quantity of the liquid pool is three, and two liquid pools therein are that liquid pool 1 and liquid pool 2 its locations of structures are located at the micro-fluidic core The sample introduction end 19 of piece, a remaining liquid pool be when liquid pool 10 its locations of structures is located at the micro-fluidic chip actual sample introduction test its The terminal 20 that liquid flows in chip, the terminal 20 is located remotely from each other with the sample introduction end 19, and one end of the pipeline is via being similarly positioned in The manifold shape turnout 3 of the interface zone being bonded to each other, should respectively with the liquid pool 1 positioned at sample introduction end 19 and the UNICOM of liquid pool 2 The other end of pipeline and a remaining liquid pool for the terminal 20 positioned at the micro-fluidic chip are the UNICOM of liquid pool 10, with And sequentially it is respectively installed in working electrode in the pipeline on diverse location and to electrode 8 and reference electrode 9, the work Make electrode by conductive electrode and the gold size sensitive membrane for having embedded cholera specific antigen being attached on the conductive electrode Form, the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of four lateral parallel connections, the work The quantity for making electrode is four, and the installation position of four working electrodes is located in four laterals respectively, this four Working electrode is working electrode 5, working electrode 6, working electrode 12, working electrode 13 respectively, and, four working electrodes its Specific antigen in the gold size sensitivity membrane structure of top layer is the four kinds of cholera antigen things that can be specifically bound to cholera antibody respectively Matter, four kinds of antigenic substances be respectively cholera TP0821 antigens and cholera TP0319 antigens and cholera TP0624 antigens and Cholera O139 antigens, for specifically deploying, 5 be the spy in its top layer gold size sensitivity membrane structure being installed in lateral 4 Specific Antigen material is the working electrode of cholera TP0821 antigens, and 6 be its top layer gold size sensitive membrane being installed in lateral 7 Specific antigenic substance in structure is the working electrode of cholera TP0319 antigens, and 12 be its table being installed in lateral 11 Specific antigenic substance in layer gold size sensitivity membrane structure is the working electrode of cholera TP0624 antigens, and 13 be to be installed in branched pipe The specific antigenic substance in its top layer gold size sensitivity membrane structure in road 14 is the working electrode of cholera O139 antigens, the work It is gold material or thermal decomposition conducting polymer material to make electrode 5, working electrode 6, working electrode 12, working electrode 13 its material Sheet or thread is presented in matter, the working electrode 5, working electrode 6, working electrode 12, working electrode 13 its pattern, and emphasis is, Its material of the substrate 15 is dimethyl silicone polymer material, and its surface of substrate 15 is the surface of primary form, the primary form Surface its be intended to refer to the primary shape of the not material by any surface chemical modification or any surface chemical modification The surface of state, the structure of the micro fluidic device also include miniature ultrasonic transducer units 18, and, higher-order of oscillation electric signal transmission electricity Cable 17, one end of the higher-order of oscillation electric signal transmission cable 17 link together with the miniature ultrasonic transducer units 18, and this is miniature Ultrasonic transducer 18 is 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 the ultrasound launched using it in the actual sample introduction test of micro-fluidic chip Ripple reduces the interfacial tension between sample solution and the inwall of the pipeline, can be compatible, also, utilizes the sample introduction The distance between end 19 and the terminal 20 and the installation position of miniature ultrasonic transducer units 18 difference and its experienced Ultrasonic intensity on difference, between its interfacial tension of sample introduction end 19 described in induced synthesis and the terminal 20 its interfacial tension Difference, the micro-fluidic chip both ends are that the interfacial tension difference between sample introduction end 19 and terminal 20 can be in the micro-fluidic chip The both ends be to form pressure gap between sample introduction end 19 and terminal 20, the pressure gap can drive sample solution to the terminal Flow in 20 directions；The ultrasonic wave that its function of the miniature ultrasonic transducer units 18 also includes being launched with it is checked contained in sample Large biological molecule its absorption on the inner surface of pipeline, and then check the dimethyl silicone polymer material substrate 15 its Swallow up effect of the body phase to the large biological molecule；Its function of the substrate 15 of the dimethyl silicone polymer material includes and cover plate 16 And working electrode 5, working electrode 6, working electrode 12, working electrode 13 and the miniflow is together built to electrode 8 and reference electrode 9 Control chip, it is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and also include with it to the strong suction of ultrasonic wave The property of receipts, ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic chip terminal to limited between the sample introduction end Short distance within realize the rapid decrement of ultrasonic intensity, when its locations of structures is located at the micro-fluidic chip actual sample introduction test A remaining liquid pool for the terminal that liquid flows is also referred to as terminal liquid pool in its chip, is filled with the terminal liquid pool High hydroscopic resin particle, its opening end of the terminal liquid pool are covered by breathable microporous film.
Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, its try The flow direction of sample liquid stream.
Miniature ultrasonic transducer units 18 and higher-order of oscillation electric signal transmission cable 17 are depicted without in Fig. 1；Also, Fig. 1 And the associate members such as the higher-order of oscillation electric signal generator and multiple tracks electrochemical workstation are depicted without in Fig. 2.
Involved miniature ultrasonic transducer units 18 are commercially available；It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal transmission cable 17 is commercially available；It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；It can also determine to relevant manufacturers System.
Each working electrode in this example structure and can be respectively via each special electricity to electrode and reference electrode Cable or say is being got lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as annex or saying interface connection of getting lines crossed.
This case device is that a variety of corresponding cholera antibody are detected with a variety of cholera antigens, thereby cholera diagnosis.

Claims (10)

1. the special cheap cholera diagnosis micro fluidic device of sap flow process mode, the structure of the micro fluidic device includes leading to more Road micro-fluidic chip, the structure of the micro-fluidic chip include being bonded to each other the substrate and cover plate of installing together, the substrate and Cover plate is plate object or tablet, and that face towards the cover plate of the substrate is contained via mould pressing process or etching technics shape Into channel structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etch work The window structure that skill or simple drilling technology are formed, it is bonded to each other the substrate being installed together and is built into jointly with the cover plate Micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the locations of structures of the pipeline are located at the substrate with being somebody's turn to do The interface zone that cover plate is bonded to each other, its side of the window is blocked by the cover plate and opposite side opens, the locations of structures of the window It is exactly the locations of structures of the liquid pool, the quantity of the liquid pool is three, and it is micro- that its locations of structures of two liquid pools therein is located at this The sample introduction end of fluidic chip, its locations of structures of a remaining liquid pool are located at its chip when the actual sample introduction of the micro-fluidic chip is tested The terminal of interior liquid flowing, the terminal are located remotely from each other with the sample introduction end, and one end of the pipeline is bonded to each other via this is similarly positioned in Interface zone manifold shape turnout respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline with positioned at should A remaining liquid pool UNICOM for the terminal of micro-fluidic chip, and, sequentially it is respectively installed in different positions in the pipeline The working electrode put and to electrode and reference electrode, the working electrode is by conductive electrode and is attached to the conduction Property electrode on embedded cholera specific antibody gold size sensitive membrane form, the construction of the pipeline is in parallel construction, described to be in The pipeline of parallel construction is made up of four lateral parallel connections, and the quantity of the working electrode is four, four working electrodes Installation position respectively in four laterals, and, its top layer gold size sensitivity membrane structure of four working electrodes In specific antigen be the four kinds of cholera antigenic substances that can be specifically bound to cholera antibody respectively, four kinds of antigenic substances point It is not cholera TP0821 antigens and cholera TP0319 antigens and cholera TP0624 antigens and cholera O139 antigens, the work Making electrode, its material is gold material or thermally decomposes conducting polymer material, and sheet or silk is presented in its pattern of the working electrode Shape, it is characterised in that its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, The surface of the primary form its be intended to refer to not by the material of any surface chemical modification or any surface chemical modification The surface of the primary form of matter, the structure of the micro fluidic device also include miniature ultrasonic transducer units, and, higher-order of oscillation telecommunication Number transmission cable, one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable link together, and this is micro- Type ultrasonic transducer is installed in the position of the cover plate of the micro-fluidic chip or the neighbouring terminal of substrate with attaching；This is miniature Its major function of ultrasonic transducer is in the test of micro-fluidic chip actual sample introduction, and the ultrasonic wave launched using it is reduced Interfacial tension between the inwall of sample solution and the pipeline, can be compatible, also, utilizes the sample introduction end and institute State on the distance between terminal and the miniature ultrasonic transducer units installation position difference and its ultrasonic intensity experienced Difference, the difference between its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension, the micro-fluidic core Interfacial tension difference between the piece both ends can form pressure gap between the both ends of the micro-fluidic chip, the pressure gap Sample solution can be driven to the end flow；Its function of the miniature ultrasonic transducer units also includes the ultrasonic wave launched with it Check in sample contained its absorption on the inner surface of pipeline of large biological molecule, and then check the polydimethylsiloxanes Swallow up effect of its body phase of the substrate of alkane material to the large biological molecule；Its function of the substrate of the dimethyl silicone polymer material Including together building the micro-fluidic chip with cover plate and working electrode and to electrode and reference electrode, it is soft and have elasticity this is poly- Its function of the substrate of dimethyl siloxane material is also included with its property to the strong absorption of ultrasonic wave, ultrasonic wave is carried out strong Absorb, and thereby realize ultrasonic intensity within micro-fluidic chip terminal to the limited short distance between the sample introduction end Rapid decrement, when its locations of structures is located at the test of the micro-fluidic chip actual sample introduction in its chip the terminal of liquid flowing institute State a remaining liquid pool and be also referred to as terminal liquid pool, some high hydroscopic resin particles, the terminal liquid pool are filled with the terminal liquid pool Its opening end is covered by breathable microporous film.
2. the special cheap cholera diagnosis micro fluidic device of sap flow process mode according to claim 1, its feature It is, 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, its feature It is, the thermal decomposition conducting polymer is the electric conductivity material formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated Material.
4. the special cheap cholera diagnosis micro fluidic device of sap flow process mode according to claim 1, its feature Be, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the length of the working electrode Degree is between 1 micron to 15000 microns.
5. the special cheap cholera diagnosis micro fluidic device of sap flow process mode according to claim 1, its feature It is, 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, its feature It is, the cover plate its material 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, its feature 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.
8. the special cheap cholera diagnosis micro fluidic device of sap flow process mode according to claim 1, its feature It is, described its thickness of cover plate and substrate in structure is between 1.0 millimeters and 5.0 millimeters.
9. the special cheap cholera diagnosis micro fluidic device of sap flow process mode according to claim 1, its feature It is, the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission cable Its other end 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, its feature It is, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 2 milliwatts and 2000 milliwatts, the miniature ultrasonic The frequency of its ultrasonic wave operationally launched of wave transducer is between 100KHz and 12MHz.
CN201610626770.6A 2016-07-26 2016-07-26 The special cheap cholera diagnosis micro fluidic device of sap flow process mode Pending CN107649191A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022187641A1 (en) * 2021-03-05 2022-09-09 The Charles Stark Draper Laboratory Inc. Actuation of microchannels for optimized acoustophoresis

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022187641A1 (en) * 2021-03-05 2022-09-09 The Charles Stark Draper Laboratory Inc. Actuation of microchannels for optimized acoustophoresis

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