CN106153890A - Comprise the easily-disassembled hypotype swine flue multi-channel testing device of electromagnetism auxiliary part - Google Patents

Comprise the easily-disassembled hypotype swine flue multi-channel testing device of electromagnetism auxiliary part Download PDF

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Publication number
CN106153890A
CN106153890A CN201510131872.6A CN201510131872A CN106153890A CN 106153890 A CN106153890 A CN 106153890A CN 201510131872 A CN201510131872 A CN 201510131872A CN 106153890 A CN106153890 A CN 106153890A
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China
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micro
substrate
fluidic chip
hypotype swine
swine flue
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CN201510131872.6A
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Inventor
王家雨
李榕生
朱云云
何家丽
吴大珍
雷克微
李天华
冯小彬
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Ningbo University
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Ningbo University
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Abstract

The present invention relates to a kind of easily-disassembled hypotype swine flue multi-channel testing device comprising electromagnetism auxiliary part, belong to analysis field tests.Use the polydimethylsiloxane inexpensively and easily processed i.e. PDMS to make a substrate physical presence series difficult problem for hypotype swine flue diagnosis micro-fluidic chip;Its surface of this PDMS material is the most hydrophobic, and surface modification or surface are modified targetedly, and its effect is difficult to persistently, and this case aims to solve the problem that this series relevant issues.This case is characterized by, the PDMS with ecosystem surface selected by substrate, and the chain ring type magnetic holding device socket being equiped with miniature ultrasonic transducer units is positioned at sample its neighbor positions of liquid stream terminal of this micro-fluidic chip, interfacial tension is reduced with ultrasound wave, utilize the PDMS strong absorbability to ultrasound wave simultaneously, reach ultrasonic intensity rapid decrement in short distance, thus form interfacial tension difference at the two ends of this chip, thereby facilitate sample liquid stream to flow to this terminal direction along capillary channel.

Description

Comprise the easily-disassembled hypotype swine flue multi-channel testing device of electromagnetism auxiliary part
Technical field
The present invention relates to a kind of easily-disassembled hypotype swine flue multi-channel testing device comprising electromagnetism auxiliary part, this device is base Diagnose the special purpose device of hypotype swine flue antigen in antigen/antibody specific reaction, belong to analysis field tests.
Background technology
Multichannel micro-fluidic hypotype swine flue diagnostic techniques background, may refer to the patent of invention Shens such as CN 201110311127.1 Please case.
Only for itself overall general picture of microflow control technique, 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 ", this monograph is published by Science Press, and this monograph is for microflow control technique Past, now, and, vision of the future etc. aspect, suffer from detailed, to be deep into detail long discussion.
So, the Important Problems that this case to be had a talk is paid close attention to.
The basic framework of micro-fluidic chip, including the substrate being etched with small fluid course and the cover plate fit together therewith, Small fluid course on described substrate, before fit on cover plate, apparent on see to be exactly some micro-channel, wait until thereon After covering cover plate, just real Guan Bi forms described small fluid course, and the conduit inner surface of this 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 completes 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 this micro-channel The state on surface or character substantially determine integrality or the character of this small fluid course;Therefore saying, this builds at base Inner surface state or the inner surface character of the micro-channel on sheet are key factors;In principle, any can keep or substantially protect Hold the material of its solid forms, can be used to make substrate and cover plate, such as, it is possible to the material as substrate and cover plate is permissible It is monocrystalline silicon piece, piezoid, sheet glass, high polymer such as polydimethylsiloxane, polymethyl methacrylate, Merlon etc. Deng;Certainly, the selection of substrate can be identical with the selection of cover plate, it is also possible to differs;From material consumption, manufacture difficulty and From the point of view of application popularization prospect etc. aspect, there is the selection of the least difference, especially that substrate between these materials, impact is relatively Greatly.
In various substrates make material, polydimethylsiloxane, i.e. PDMS, the easiest molding, so Substrate on to make micro-channel extremely simple, and this lower cost for material, make substrate with this polydimethyl siloxane material, Suppress or etch micro-channel thereon, and the cover plate made with glass or the cheap material such as polypropylene or other plastic sheet matches, 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, promote.
But, thing is really not so simply.
One, this polydimethyl siloxane material, the material that i.e. abbreviation letter PDMS is referred to, itself is a kind of strong Hydrophobic material, builds micro-channel on this material, if not carrying out the modified operation for this micro-channel surface, then, After entirety has been assembled, after i.e. covering cover plate, lead to because its inner surface of described micro-channel in structure occupies most liquid stream The inner surface in road, then, this its strong hydrophobic property of PDMS micro-channel inner surface, is deciding factor, and it can make class Be similar to aqueous solution the fine liquid stream of polar liquid by becoming the most difficult, its flow resistance is big, and the most general Micropump is all It is difficult to promote, certainly, if cover plate also selects to use this PDMS material, then, problem is substantially identical, similar; Therefore, among prior art, it is modified modifying particular for the micro-channel inner surface on this PDMS material, is necessary Operation;So, this operates pretty troublesome for the modification of PDMS micro-channel inner surface?That is not this problem, structure Become serious technical puzzlement, be another problem: the PDMS polymer molecule tool that this its body of PDMS material substrate is internal mutually Having the characteristic automatically diffusing to the surface, migrating, this substrate body internal PDMS polymer molecule mutually automatically diffuses to the surface, moves The characteristic moved, can not maintain foot by making the state after the modification of that its inner surface of micro-channel of surface modification modification The enough long time, holding time of its inner surface state of the micro-channel after that is surface-modified has substantially been only sufficient in laboratory The time of portion's test experiments needs;In other words, through this PDMS micro-channel inner surface that surface modification or surface are modified, its After modification or say the apparent condition formed after modification can not be lasting, but automatically tend to soon or say become surface again and change Apparent condition before property, returns to the most hydrophobic apparent condition of that script in relatively short period of time, then, just think, Such micro-fluidic chip can make in a large number, mass storage, be widely popularized, and answer is clearly, that is, it is impossible to. Micro-channel on this PDMS material, if not doing surface modification, the fine liquid stream of polar solvent being similar to aqueous solution cannot pump Sending and pass through, chip the most just cannot use;And if done surface modification, the state after cannot persistently keeping again it to modify, also It is equally cannot popularization and application.
So, how to accomplish to utilize cheap PDMS material to make substrate, and table in described micro-channel can be released Face decorating state cannot persistently, chip cannot make in a large number, lay in a large number and then be widely popularized and such a make this area numerous specially The puzzlement that industry personnel are entangled with for a long time, it is simply that the highly difficult problem that its obvious technology barrier can not be despised.
Having there are a lot of days in this highly difficult problem, up to now, is not yet properly settled.
Its two, the PDMS material of non-surface modification, above it is stated that, its surface is the most hydrophobic, this most hydrophobic Material surface and also another problem, that is, biomacromolecule can be adsorbed in the most hydrophobic this PDMS surface, and And, the depression that these adsorbed biomacromolecules also can be further on PDMS surface further, gradually falls into gradually deep, directly To the heavy body phase being trapped in PDMS substrate, in fact, this process, partly it is also due to PDMS material body internal mutually Polymer molecule have diffuse to the surface, travel motion is caused;This situation, it is also possible to explain from another angle, i.e. Internal to its diffusion into the surface, those polymer molecules of migration, the result of its motion mutually by PDMS body continuously, be by Within those gradually have been involved in the body phase of PDMS substrate by the biomacromolecule of surface adsorption, briefly, these are inhaled Attached biomacromolecule is swallowed up mutually by PDMS substrate body exactly;So, this PDMS substrate body swallows up biomacromolecule mutually Phenomenon, its impact caused, necessarily cause the severe deviations relating to all kinds of test data of experiment of biomacromolecule.
As it has been described above, the problem of PDMS substrate is, its not only surface adsorption biomacromolecule, and swallow up biomacromolecule, So, its disappearance of biomacromolecule as experiment test object will not stop because of the saturated absorption in surface, but, no Disconnected adsorbed, the most constantly swallowed up.
About PDMS substrate in related experiment test process its body the most constantly swallow up test associated biomolecule macromole phenomenon, separately A kind of explanation is to say, PDMS body mutually in there is substantial amounts of Minute pores, associated biomolecule macromole by after surface adsorption, depression Enter these Minute pores, and then swallowed up;But, inventor thinks, those can allow that the air of miniature scale divides Son clamp-ons described Minute pores therebetween, is not equal to them and also can directly allow that the biomacromolecule of relatively large yardstick enters, and two Person's difference on yardstick is huge, must not make sweeping generalizations.Bypass explanation, in any case, analyze the biology of object as dependence test Macromole is adsorbed by PDMS substrate micro-channel inner surface, and then is constantly swallowed up by PDMS substrate body phase, and this is known objective The phenomenon existed.
In order to stop the effect of swallowing up relative to biomacromolecule of this PDMS substrate body, can be from containment PDMS surface to life The absorption of thing macromole addresses, and way is aiming at this PDMS material surface and is chemically modified modification, for From the point of view of PDMS is the situation of substrate material, it is simply that the surface of described micro-channel part is chemically modified modification, Jing Guohua Learn the described micro-channel inner surface of modification, it is possible to contain its absorption to biomacromolecule, and then avoid biomacromolecule quilt PDMS substrate body is swallowed up mutually;But, or that old problem, that is, the chemical modification on PDMS material surface changes Apparent condition after property cannot persistently keep, the internal mutually polymer molecule of this PDMS substrate body its automatically diffuse to the surface, The process migrated, can become that again script strong through the micro-channel inner surface state that surface chemical modification is modified soon and dredge Water and the state of strong adsorption biomacromolecule, in other words, no matter how professionals in the field turn from side to side, this PDMS Its micro-channel inner surface of substrate is the most rapidly to strong hydrophobic surface state evolution.
So, how can either obtain that PDMS material price is the cheapest, substrate makes extremely easy benefit, can reach again Growth stage contains this PDMS substrate micro-channel inner surface absorption process to biomacromolecule, and then stops PDMS substrate body phase The effect of swallowing up to biomacromolecule so that related chip manufactured goods are able to maintain that a shelf-life the most long, rational, It it is exactly a difficult problem the most thorny.This difficult problem, as another difficult problem addressed above, makes the numerous specialty in this area equally Personnel are entangled with for a long time, perplex, and this difficult problem is the highly difficult problem that its obvious technology barrier can not be despised equally.This difficulty Having there are a lot of days in topic, up to now, is the most not yet properly settled.
Summary of the invention
The technical problem to be solved is to provide a package solution, solves to address above totally Two difficult problems, and, this solution is applied to hypotype swine flue diagnosis multichannel micro-fluidic chip field, forms one Novel hypotype swine flue diagnosis Multichannel device.
The present invention solves described technical problem by following scheme, and the device that the program provides is that one comprises electromagnetism auxiliary part Easily-disassembled hypotype swine flue multi-channel testing device, the structure of this device includes multichannel micro-fluidic chip, this micro-fluidic core The structure of sheet includes bonded to each other being installed in substrate together and cover plate, and described substrate and cover plate are plate object or tablet, should The channel structure formed via mould pressing process or etching technics is contained in that face towards this cover plate of substrate, this substrate possibly together with This channel structure is connected and pierces the window knot formed via mould pressing process, etching technics or simple drilling technology of this substrate Structure, this substrate being installed together bonded to each other and this cover plate have been built into jointly containing pipeline configuration and the liquid pool that is attached thereto The micro-fluidic chip of structure, the locations of structures of this pipeline is positioned at the interface zone that this substrate is bonded to each other with this cover plate, this window its Side is blocked by this cover plate and opposite side is open, and the locations of structures of this window is exactly the locations of structures of described liquid pool, described liquid pool Quantity is three, and two its locations of structures of liquid pool therein are positioned at the sample introduction end of this micro-fluidic chip, its knot of a remaining liquid pool The terminal of its chip liquid flowing when structure position is positioned at the test of this micro-fluidic chip actual sample introduction, this terminal is mutual with this sample introduction end Away from, one end of this pipeline via be similarly positioned in the manifold shape turnout of this interface zone bonded to each other respectively be positioned at sample introduction end This Liang Ge liquid pool UNICOM, this remaining liquid pool connection of the other end of this pipeline and the described terminal being positioned at this micro-fluidic chip Logical, and, the working electrode that is sequentially respectively installed in this pipeline on diverse location and to electrode and reference electrode, described Working electrode is by conductive electrode and the gold size having embedded hypotype swine flue specific antibody that is attached on this conductive electrode Sensitive membrane is constituted, and the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is made up of three lateral parallel connections, The quantity of described working electrode is three, and the installation position of these three working electrodes lays respectively in described three laterals, with And, the specific antibody in its top layer gold size sensitive membrane structure of these three working electrodes is can be special to hypotype swine flue antigen respectively Property combine three kinds of hypotype swine flue antibody materials, these three kinds of antibody materials are hypotype swine flue specific antibody H respectively1N1、H3N2 And H1N2, its material of described working electrode be gold material or thermal decomposition conducting polymer material, its pattern of described working electrode in Existing lamellar or thread, it is important that, its material of this substrate is polydimethylsiloxane material, and its surface of this substrate is primary form Surface, the surface of this primary form its be intended to refer to not through any surface chemical modification or any surface chemical modification should The surface of the primary form of material, the structure of this device also includes chain ring type magnetic holding device, in this its structure of chain ring type magnetic holding device Have six links, described link all in strip, shaft-like or bar-shaped, each adjacent link is hinged formation chain link, this chain link its The hexagonal circulus of appearance profile, its locations of structures of each drift angle of this hexagonal annular structure is articulated structure position, This hexagonal annular structure two its materials of link being in opposite side position therein are magnetic conductivity materials, this hexagonal annular structure Its material of remaining four processes be all non-magnetic material, described non magnetic material refers to the most strongly to respond externally-applied magnetic field Material, a link among two links of this magnetic conductivity material is wound with magnet exciting coil, and this is wound with the ring of magnet exciting coil Joint is respectively equiped with the pole shoe of a magnetic conductivity material in the both sides neighbor positions of its magnet exciting coil, has two described pole shoes, should Two pole shoes are directed to the link of another magnetic conductivity material, and its surface of the link of this another magnetic conductivity material attaches fixing dress Be provided with miniature ultrasonic transducer units, rely on this chain ring type magnetic holding device socket of electromagnetism adhesive strength be positioned at this micro-fluidic chip its The close position of described terminal, and, higher-order of oscillation electric signal transmission cable, one end of this higher-order of oscillation electric signal transmission cable Link together with this miniature ultrasonic transducer units;This chain ring type magnetic holding device provides a function facilitating this device to disassemble; Its major function of this miniature ultrasonic transducer units is when the actual sample introduction of micro-fluidic chip is tested, and utilizes its ultrasound wave launched Reduce the interfacial tension between sample solution and the inwall of described pipeline so that it is can be compatible, and, utilize described sample introduction end with And the distance difference between described terminal and this miniature ultrasonic transducer units installation position and its ultrasonic intensity experienced On difference, difference between its interfacial tension of sample introduction end and its interfacial tension of described terminal described in induced synthesis, this micro-fluidic core Interfacial tension difference between these two ends of sheet can form pressure gap, this pressure gap meeting between these two ends of this micro-fluidic chip Drive sample solution to described end flow;Its function of this miniature ultrasonic transducer units also includes checking with its ultrasound wave launched Its absorption on described inner surface of pipeline of biomacromolecule contained in sample, and then check this polydimethylsiloxane material Its body of substrate relative to the effect of swallowing up of this biomacromolecule;Its function of substrate of described polydimethylsiloxane material includes and lid Sheet and working electrode and electrode and reference electrode are together built this micro-fluidic chip, soft this polydimethylsiloxanes also having elasticity Its function of the substrate of alkane material also includes, with the character of its absorption strong to ultrasound wave, strongly absorbing ultrasound wave, and thereby The rapid decrement of ultrasonic intensity is realized within limited short distance between this terminal of this micro-fluidic chip to this sample introduction end.
Itself art-recognized meanings of described magnet exciting coil one word is known.
Itself art-recognized meanings of described magnetic conductivity material one word is known;Belong to magnetic conductivity material material such as pure iron, Silicon steel, soft magnetic ferrite etc..
Non magnetic material described in this case refers to the material the most strongly responded externally-applied magnetic field, belongs to described non magnetic material Material such as metallic copper, metallic zinc, ormolu, metallic aluminium, almag etc..
Itself art-recognized meanings field in Machine Design of a described hinged word is known.
Described gold size sensitive membrane is to be sufficiently mixed uniformly by chitosan gold size solution and hypotype swine flue specific antibody solution, uses Point sample instrument point sample or coat specified structure position, and make its drying and forming-film form.Hypotype swine flue in described gold size sensitive membrane Specific antibody is the hypotype swine flue antibody of horseradish peroxidase or glucose oxidase labelling, described gold size sensitive membrane Being included as fixing above-mentioned each hypotype swine flue specific antibody and introduced complementary medium therein, described complementary medium is such as Chitosan, cellulose acetate, gelatin be therein a kind of or their mixture.
Described pipeline in described microfluidic chip structure and described lateral and described manifold shape turnout, its internal diameter chi Very little may each be arbitrarily selected size, but, for less with the consideration of the aspects such as liquid sample to be measured and reduction reagent loss, Described pipeline and described lateral and described manifold shape turnout the most all select the passage of capillary level, described capillary level Passage imply that the passage that the internal diameter of capillary tube on its internal diameter and ordinary meaning is suitable.Described its inner passage of capillary tube transversal Face shape can be arbitrary shape, described shape of cross section is the most circular, oval, square, rectangle, bar shaped, the most also Can be arbitrary to there is the linear of bending, and, the interior shape of described capillary tube along with the extension of pipeline, different parts Shape of cross section can also allow to be different shapes.Only for capillary tube one word, its art-recognized meanings is known.
Relate in structure is minute sized electrode to electrode and reference electrode, and its electrode shape may each be arbitrarily choosing Fixed shape, described arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..Described to electricity Itself the art-recognized meanings of vocabulary of pole and described reference electrode is known.
Relating to several liquid pools in this case microfluidic chip structure, described liquid pool is the pond shape for transitional liquid storage or scrotiform structure Making, its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, described 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 described liquid pool can be arbitrarily selected Size, but, in order to as far as possible less by liquid sample to be measured and reduction reagent loss, described liquid pool is preferably capable of and capillary tube The hypomegetic liquid pool of coupling.
Only for itself the art-recognized meanings of the ultrasonic transducer one word professional for ultrasonic technology field, it is public Know.
Various sizes, variously-shaped ultrasonic transducer are commercially available;Its size of commercially available miniature ultrasonic transducer units is permissible Little to the magnitude only calculated with millimeter.
Only with regard to its technique for fixing on general industry application solid body surface of miniature ultrasonic transducer units itself and Speech, for the professional in ultrasonic technology field, is known general technology.This is not launched superfluous words by this case.
Only itself micro-channel of naked PDMS substrate is molded or for lithographic technique, be open-and-shut known technology;With Sample ground, the technology of hole-opening known simple technique especially on naked PDMS substrate.This is not launched superfluous words by this case.
The industrial products market of involved higher-order of oscillation electric signal its all size of transmission cable is the most on sale.
The structure of this device can also include higher-order of oscillation electric signal generator;It is another for described higher-order of oscillation electric signal transmission cable One end can be connected with this higher-order of oscillation electric signal generator.
Itself technology of involved higher-order of oscillation electric signal generator, for the professional in ultrasonic technology field, be Simple and known;Described higher-order of oscillation electric signal generator can customize to ultrasonic instrument specialized factory.
The preferred scope of its specified ultrasonic emitting power of this miniature ultrasonic transducer units be between 5 milliwatts and 9000 milliwatts it Between;The preferred scope of the frequency of its ultrasound wave operationally launched of this miniature ultrasonic transducer units be between 100KHz with Between 12MHz.
This case device can further include some adnexaes certainly, described adnexa such as multiple tracks electrochemical workstation etc., institute The art-recognized meanings stating multiple tracks electrochemical workstation is known.Each working electrode of relating in this case microfluidic chip structure and To electrode and reference electrode etc., can be respectively via the most special the corresponding interface got lines crossed with described multiple tracks electrochemical workstation Couple.Described special each the corresponding interface being used to each described electrode with described multiple tracks electrochemical workstation of getting lines crossed is carrying out phase The private cable being mutually coupled with.Described micro-fluidic chip in this case device, its structure can also include micro-valve, the number of described micro-valve Amount does not limits, according to actual needs, and any need position to be mounted that described micro-valve can be installed in this microfluidic chip structure; This micro-valve one word is for the professional of micro fluidic chip technical field, and the art-recognized meanings of itself is known;This micro-valve The manufacturing technology of itself and use technology are also known;This optional component of micro-valve.
The diameter of described working electrode can allow the suitable diameter being easily installed use being arbitrarily set, it is however recommended to Or say preferred its scope of described diameter between 0.1 micron to 2000 micron;The length of described working electrode can permit Permitted the length being easily installed use being arbitrarily set, it is however recommended to or to say preferred its scope of described length be at 1 micron Between 15000 microns.
The described gold size being installed in described working electrode surface layer by spraying or point sample instrument point sample or the coating of other appropriate process is quick Sense film, its thicknesses of layers can allow the thickness that the sample measuring liquid the treated generation electrical signals being arbitrarily set responds, but, push away The thickness recommended the most preferably thickness is between 10 nanometers and 200 nanometers.
Described cover plate in chip structure, its material can allow to be any electrical insulating property material, such as: polypropylene, glass Glass, polymethyl methacrylate, polydimethylsiloxane, etc., in order to make smaller size of micro-fluidic chip, such as do Become the micro-fluidic chip of the super-small of length only 2.0 centimetres to 3.0 centimetres, and realize ultrasound wave in the distance that this is extremely short Extremely fast decay, it may be preferred to polydimethylsiloxane is used as cover plate.Certainly, large-sized micro-fluidic chip selects Use polydimethylsiloxane to be used as described cover plate, be also that this case technical scheme is allowed.
Be positioned at this micro-fluidic chip this sample introduction end these two liquid pools its with to be positioned at this of this this terminal of micro-fluidic chip remaining Air line distance between one liquid pool can be arbitrarily selected suitable distance as required, but, the preferred value of this distance is Between 3 centimetres and 7 centimetres.
Described cover plate and its thickness of substrate can allow the thickness being easy to assembling being arbitrarily set, it is recommended that thickness or say preferably Thickness be between 1.0 millimeters and 5.0 millimeters.Less thickness is conducive to saving material.
The using method of this case micro-fluidic chip:
Propose first based on this case and this first public novel liquid stream driving principle, its application running of this case micro-fluidic chip In, this novel liquid stream driving method determines completely without involving any additional Micropump.
This interfacial tension difference formed between these two ends of this micro-fluidic chip that this case is caused with described ultrasound wave, drives liquid Stream flows in the capillary channel of this triple channel micro-fluidic chip, utilizes multi-channel electrochemical analyzer device respectively to three kinds of hypotypes Swine flue diagnostic antigen is detected.
The concrete detection of this case micro-fluidic chip uses step as follows:
1, adding blood serum sample liquid in micro-pipeline, under described ultrasound wave drives, various hypotype swine flue antigen molecules are by respectively The hypotype swine flue specific antibody of the corresponding horseradish peroxidase-labeled of gold size sensitive membrane embedding on electrode surface in passage Capture.
2, the hypotype swine flue specific antibody of horseradish peroxidase-labeled is formed with the hypotype swine flue antigen in blood serum sample Immune complex.
3, use multi-channel electrochemical analyzer, add the electron mediators such as catechol, use the above-mentioned reaction of amperometric detection The curent change caused, is derived from kind and the content of various analyte.
4, result is comprehensively analyzed, hypotype swine flue antigen is carried out comprehensive diagnos.
It is an advantage of the invention that its close position of described terminal at described micro-fluidic chip relies on the socket of electromagnetism adhesive strength fixed Chain ring type magnetic holding device described in Wei, with in this chain ring type magnetic holding device one magnetic conductivity link attaching install miniature ultrasonic Wave transducer, utilizes its low-power launched, the ultrasound wave of high-frequency band so that without surface chemical modification or come to the surface The compatibility learned between this most hydrophobic its tube wall of micro-fluidic chip internal pipeline modified and test object water solution significantly increases Add, this for sample liquid stream by providing a realistic possibility;Meanwhile, utilize polydimethylsiloxane substrate its to ultrasonic The strong absorbability of ripple, in comparatively short distance, it is, the only several centimeters from described terminal to described sample introduction end In the shortest distance of yardstick, reaching the rapid decrement of ultrasonic intensity, thereby institute is caused at the described two ends at this micro-fluidic chip State the difference of interfacial tension, and then, utilize the pressure between its these two ends formed of difference of the interfacial tension between these two ends Difference, drives sample liquid stream to flow to described terminal direction in the capillary channel that such a is the most hydrophobic.By this Case liquid stream drive scheme, entirely without the substrate of this polydimethylsiloxane material and internal pipeline thereof being carried out any coming to the surface Learn and modify or chemical modification, altogether dispensed with the laborious procedures of this surface chemical modification or chemical modification;And altogether dispense with biography The equipment of the Micropump in system meaning etc;On the other hand, the ultrasound wave of this low-power, high-frequency band, additionally it is possible in containment sample Biomacromolecule absorption on this literalness naked its inner surface of pipeline of polydimethylsiloxane substrate, and then contain that this gathers The effect of swallowing up of the most described biomacromolecule of its body of dimethyl siloxane sheet;Described antigen, antibody and antigen and antibody Reversible binding thing is the most all belonging to the type of described biomacromolecule;Due to described adsorption and the described work that swallows up With effectively being contained, therefore, dependence test result will be better able to reflect practical situation objectively;This low-power, height are again and again The effect of section ultrasound wave, the most also includes facilitating what the Reversible binding between antigen, antibody reacted quickly to reach, and this makes to be correlated with Test operation can be to complete than speed faster.
Owing to being made without the surface chemical modification for this polydimethylsiloxane its relevant surfaces of substrate or chemical modification behaviour Making, therefore, this surface chemical modification layer or chemically modified layer not need to exist, then, this polydimethylsiloxane Its body phase interior polymeric thing molecule of substrate diffuses to the surface the most automatically, migrate it caused to described surface chemical modification layer or The damaging influence of chemically modified layer does not exists.
The technical scheme of this case has dissolved relevant to its application of polydimethylsiloxane substrate addressed above totally Row technical barrier.Based on this case scheme, the most cheap polydimethyl siloxane material of this kind is the most likely at this micro-fluidic chip Prepare, produce, application etc. field plays bigger effect.
Attach in this chain ring type magnetic holding device one magnetic conductivity link in this case structure to fix and installed described miniature ultrasonic Transducer, this architecture provides a function facilitating this device to disassemble, and so, this chain ring type magnetic holding device is led together with one The miniature ultrasonic transducer units attached in magnetic link just can be mutually disengaged with this micro-fluidic chip easily, then, this portion Divide the component that can freely depart from just can reuse many times with circulating benignly;This architectural feature is conducive to saving making of this device Use cost.
Accompanying drawing explanation
Fig. 1 is the schematic diagram of this device embodiment chip part of this case structure, it is shown that the depression angle of this example structure Under chip internal pipeline and each electrode and the configuration of each relevant liquid pool, this figure is not depicted described chain ring type electromagnetic clamp The miniature ultrasonic transducer units having and set up on it and other described adnexa.
Fig. 2 is its outside side view rough with under this micro-fluidic chip socket state of this chain ring type magnetic holding device of this device of this case, This legend and indicate under this socket state the relative position relation between each component.
Fig. 3 is the outside side view under another viewing angle of this device of this case;The viewing angle of Fig. 3 and the sight of Fig. 2 Examine angle to be mutually perpendicular to.
In figure, 1,2,8 is the liquid pool that three installation positions are different respectively, and 3 is manifold shape turnout, and 4,9,12 are respectively Installation position is different but three laterals forming UNICOM in parallel structure parallel with one another, and 5 is its that be installed in lateral 4 Specific antibody material in the gold size sensitive membrane structure of top layer is hypotype swine flue specific antibody H1N1Working electrode, 10 are Specific antibody material in its top layer gold size sensitive membrane structure being installed in lateral 9 is that hypotype swine flue specificity resists Body H3N2Working electrode, 11 is the specific antibody thing in its top layer gold size sensitive membrane structure being installed in lateral 12 Matter is hypotype swine flue specific antibody H1N2Working electrode, 6 is to electrode, and 7 is reference electrode, and 13 is chain ring type electromagnetism Fixture, 14 is the described terminal of this micro-fluidic chip, and 15 is the described sample introduction end of this micro-fluidic chip, and 16 is poly dimethyl silicon The substrate of oxygen alkane material, 17 is cover plate, and 18 is miniature ultrasonic transducer units, and 19 is higher-order of oscillation electric signal transmission cable, 20, The link of 27 two the magnetic conductivity materials being in different structure position respectively, the link of these two magnetic conductivity materials is in this structure In end-to-end relation each other, 21,34 are in two pole shoes of different structure position respectively, 22,24,26,29,31,33 Being in six pin joints of six diverse locations respectively, 23,25,30,32 are in four of four diverse locations respectively The link of non magnetic material, 28 is magnet exciting coil;This chain ring type magnetic holding device structure in legend is only the legend structure of signal, This chain ring type magnetic holding device structure actual is not limited to this legend chain ring type magnetic holding device structure;It is micro-that arrow in legend indicates this Fluidic chip its when actual motion, driven by pressure at two ends difference, the flow direction of its sample liquid stream.
Detailed description of the invention
In this embodiment of this case that Fig. 1, Fig. 2 and Fig. 3 are shown, the structure of this device includes multichannel micro-fluidic chip, The structure of this micro-fluidic chip includes bonded to each other being installed in substrate 16 together and cover plate 17, described substrate 16 and cover plate 17 Being plate object or tablet, that face towards this cover plate 17 of this substrate 16 is contained via mould pressing process or etching technics shape Become channel structure, this substrate 16 possibly together be connected with this channel structure and pierce this substrate 16 via mould pressing process, quarter The window structure that etching technique or simple drilling technology are formed, this substrate 16 being installed together bonded to each other is common with this cover plate 17 Being built into containing pipeline configuration and the micro-fluidic chip of liquid pool structure that is attached thereto, the locations of structures of this pipeline is positioned at this base The interface zone that sheet 16 is bonded to each other with this cover plate 17, its side of this window is blocked by this cover plate 17 and opposite side is open, should The locations of structures of window is exactly the locations of structures of described liquid pool, and the quantity of described liquid pool is three, and these three liquid pools are liquid pool respectively 1, liquid pool 2, liquid pool 8, the i.e. liquid pool 1 of two liquid pools therein and its locations of structures of liquid pool 2 are positioned at the sample introduction of this micro-fluidic chip End 15, its chip liquid when a remaining liquid pool i.e. its locations of structures of liquid pool 8 is positioned at the test of this micro-fluidic chip actual sample introduction The terminal 14 of body flowing, this terminal 14 is located remotely from each other with this sample introduction end 15, and one end of this pipeline is mutual via being similarly positioned in this The manifold shape turnout 3 of the interface zone of laminating respectively be positioned at this two liquid pools i.e. liquid pool 1 and liquid pool 2 UNICOM of sample introduction end 15, This remaining liquid pool i.e. liquid pool 8 UNICOM of the other end of this pipeline and the described terminal 14 being positioned at this micro-fluidic chip, with And, the working electrode that is sequentially respectively installed in this pipeline on diverse location and to electrode and reference electrode, described work electricity Pole is by conductive electrode and the gold size sensitive membrane having embedded hypotype swine flue specific antibody that is attached on this conductive electrode Constituting, the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is made up of three lateral parallel connections, described work The quantity making electrode is three, and the installation position of these three working electrodes lays respectively in described three laterals, and, should Specific antibody in three its top layer gold size sensitive membrane structures of working electrode is to tie hypotype swine flue antigen energy specificity respectively The three kinds of hypotype swine flue antibody materials closed, these three kinds of antibody materials are hypotype swine flue specific antibody H respectively1N1、H3N2And H1N2, from the point of view of concrete expansion, 5 is the specific antibody thing in its top layer gold size sensitive membrane structure being installed in lateral 4 Matter is hypotype swine flue specific antibody H1N1Working electrode, 10 is that its top layer gold size being installed in lateral 9 is sensitive Specific antibody material in membrane structure is hypotype swine flue specific antibody H3N2Working electrode, 11 is to be installed in branched pipe The specific antibody material in its top layer gold size sensitive membrane structure in road 12 is hypotype swine flue specific antibody H1N2Work Electrode, its material of described working electrode is gold material or thermal decomposition conducting polymer material, and its pattern of described working electrode presents Lamellar or thread, it is important that, this its material of substrate 16 is polydimethylsiloxane material, and this its surface of substrate 16 is primary The surface of form, the surface of this primary form its be intended to refer to not change through any surface chemical modification or any surface chemistry The surface of the primary form of this material of property, the structure of this device also includes chain ring type magnetic holding device 13, this chain ring type electromagnetic clamp Having six links in tool 13 its structures, these six links are link 20,23,25,27,30,32 respectively, described ring Joint 20,23,25,27,30,32 all in strip, shaft-like or bar-shaped, each adjacent link is hinged formation chain link, this chain The hexagonal circulus of its appearance profile of ring, each drift angle 22,24,26,29,31,33 of this hexagonal annular structure Its locations of structures is articulated structure position, this hexagonal annular structure two links 20,27 being in opposite side position therein Its material is magnetic conductivity material, and its material of remaining four processes 23,25,30,32 of this hexagonal annular structure is all non-magnetic Property material, described non magnetic material refers to the material the most strongly responded externally-applied magnetic field, two links of this magnetic conductivity material 20, being wound with magnet exciting coil 28 in a link 27 among 27, this link 27 being wound with magnet exciting coil 28 is encouraged at it Respectively it is equiped with the pole shoe of a magnetic conductivity material in the both sides neighbor positions of magnetic coil 28, has two described pole shoes, described pole Boots are pole shoe 21 and pole shoe 34 respectively, and these two pole shoes 21,34 are directed to the link 20 of another magnetic conductivity material, and this is another The fixing miniature ultrasonic transducer units 18 that is equiped with, support electromagnetism the suction-combining force is attached on its surface of link 20 of one magnetic conductivity material This chain ring type magnetic holding device 13 socket of amount is positioned at the close position of its described terminal 14 of this micro-fluidic chip, and, high Frequency vibration swings electric signal transmission cable 19, one end of this higher-order of oscillation electric signal transmission cable 19 and this miniature ultrasonic transducer units 18 link together;This chain ring type magnetic holding device 13 provides a function facilitating this device to disassemble;This miniature ultrasonic changes Can its major function of device 18 be when the actual sample introduction of micro-fluidic chip is tested, utilize its ultrasound wave launched molten to reduce sample Interfacial tension between the inwall of liquid and described pipeline so that it is can be compatible, and, utilize described sample introduction end 15 and described Distance difference between terminal 14 and this miniature ultrasonic transducer units 18 installation position and its ultrasonic intensity experienced On difference, difference between its interfacial tension of sample introduction end 15 and its interfacial tension of described terminal 14 described in induced synthesis, should Interfacial tension difference between these two ends of micro-fluidic chip can form pressure gap, this pressure between these two ends of this micro-fluidic chip Power difference can drive sample solution to flow to described terminal 14;This its function of miniature ultrasonic transducer units 18 also includes with its institute The ultrasound wave launched checks its absorption on described inner surface of pipeline of biomacromolecule contained in sample, and then it is poly-to check this Its body of substrate 16 of dimethyl siloxane material is relative to the effect of swallowing up of this biomacromolecule;Described polydimethylsiloxane material Its function of substrate 16 include and cover plate 17 and working electrode 5,10,11 and electrode 6 and reference electrode 7 are together built This micro-fluidic chip, soft and this polydimethylsiloxane material of having elasticity its function of substrate 16 also includes with it ultrasonic The character that ripple absorbs strongly, absorbs strongly to ultrasound wave, and thereby arrives this sample introduction end in this terminal 14 of this micro-fluidic chip The rapid decrement of ultrasonic intensity is realized within limited short distance between 15.
Arrow in legend indicate this micro-fluidic chip its when actual motion, driven by pressure at two ends difference, its test liquid The flow direction of stream.
Fig. 1 is depicted without in this chain ring type magnetic holding device 13 and one magnetic conductivity material link 20 being attached installing This miniature ultrasonic transducer units 18 and higher-order of oscillation electric signal transmission cable 19, and, magnet exciting coil 28 component such as grade;And And, Fig. 1, Fig. 2 and Fig. 3 are all depicted without described higher-order of oscillation electric signal generator and multiple tracks electrochemical workstation etc. attached Part.
Involved miniature ultrasonic transducer units 18 is commercially available;Can also customize to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal transmission cable 19 is commercially available;Can also customize to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available;Can also customize to relevant manufacturers.
Each working electrode in this example structure and can be respectively via the most special cable or say to electrode and reference electrode Get lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as adnexa or say interface of getting lines crossed and couple.
The configuration of this chain ring type magnetic holding device 13 in legend is only an example, chain ring type magnetic holding device described in this case Configuration is not limited to the version in this legend.

Claims (10)

1. comprising the easily-disassembled hypotype swine flue multi-channel testing device of electromagnetism auxiliary part, the structure of this device includes multichannel Micro-fluidic chip, the structure of this micro-fluidic chip includes bonded to each other being installed in substrate together and cover plate, described substrate and cover plate Being plate object or tablet, the groove formed via mould pressing process or etching technics is contained in that face towards this cover plate of this substrate Road structure, this substrate possibly together be connected with this channel structure and pierce this substrate via mould pressing process, etching technics or simple The window structure that drilling technology is formed, this substrate being installed together bonded to each other and this cover plate have been built into jointly to be tied containing pipeline Structure and the micro-fluidic chip of liquid pool structure being attached thereto, it is bonded to each other with this cover plate that the locations of structures of this pipeline is positioned at this substrate Interface zone, its side of this window is blocked by this cover plate and opposite side is open, and the locations of structures of this window is exactly described liquid pool Locations of structures, the quantity of described liquid pool is three, and two its locations of structures of liquid pool therein are positioned at the sample introduction end of this micro-fluidic chip, The terminal of its chip liquid flowing when remaining its locations of structures of liquid pool is positioned at the test of this micro-fluidic chip actual sample introduction, should Terminal is located remotely from each other with this sample introduction end, and one end of this pipeline is via the manifold shape turnout being similarly positioned in this interface zone bonded to each other Respectively be positioned at this Liang Ge liquid pool UNICOM of sample introduction end, the other end of this pipeline be positioned at this micro-fluidic chip described terminal should A remaining liquid pool UNICOM, and, the working electrode that is sequentially respectively installed in this pipeline on diverse location and to electrode with And reference electrode, described working electrode by conductive electrode and be attached on this conductive electrode to have embedded hypotype swine flue special The gold size sensitive membrane of heterogenetic antibody is constituted, and the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is by three branches Pipeline parallel connection is constituted, and the quantity of described working electrode is three, and the installation position of these three working electrodes lays respectively at described three In lateral, and, the specific antibody in its top layer gold size sensitive membrane structure of these three working electrodes is to hypotype pig respectively Three kinds of hypotype swine flue antibody materials that influenza antigens energy is specific binding, these three kinds of antibody materials are that hypotype swine flue is special respectively Property antibody H1N1、H3N2And H1N2, its material of described working electrode is gold material or thermal decomposition conducting polymer material, described work Make its pattern of electrode and present lamellar or thread, it is characterised in that its material of this substrate is polydimethylsiloxane material, this substrate Its surface is the surface of primary form, the surface of this primary form its be intended to refer to not through any surface chemical modification or appoint The surface of the primary form of this material of what surface chemical modification, the structure of this device also includes chain ring type magnetic holding device, this chain link Its structure of formula magnetic holding device has six links, described link all in strip, shaft-like or bar-shaped, each adjacent link is hinged Form chain link, the hexagonal circulus of its appearance profile of this chain link, its locations of structures of each drift angle of this hexagonal annular structure Being articulated structure position, this hexagonal annular structure two its materials of link being in opposite side position therein are magnetic conductivity materials Matter, its material of remaining four processes of this hexagonal annular structure is all non-magnetic material, and described non magnetic material refers to externally Add the material that magnetic field responds the most strongly, a link among two links of this magnetic conductivity material be wound with magnet exciting coil, This is wound with the link of magnet exciting coil and is respectively equiped with the pole shoe of a magnetic conductivity material in the both sides neighbor positions of its magnet exciting coil, Having two described pole shoes, these two pole shoes are directed to the link of another magnetic conductivity material, the ring of this another magnetic conductivity material Save and on its surface, attach the fixing miniature ultrasonic transducer units that is equiped with, this chain ring type magnetic holding device socket of support electromagnetism adhesive strength It is positioned at the close position of its described terminal of this micro-fluidic chip, and, higher-order of oscillation electric signal transmission cable, this higher-order of oscillation One end of electric signal transmission cable links together with this miniature ultrasonic transducer units;This chain ring type magnetic holding device provides a side Just the function that this device is disassembled;Its major function of this miniature ultrasonic transducer units is when the actual sample introduction of micro-fluidic chip is tested, profit The interfacial tension between the inwall of sample solution and described pipeline is reduced so that it is can be compatible with its ultrasound wave launched, and And, utilize the distance difference between described sample introduction end and described terminal and this miniature ultrasonic transducer units installation position and its institute The difference on ultrasonic intensity experienced, described in induced synthesis between its interfacial tension of sample introduction end and its interfacial tension of described terminal Difference, the interfacial tension difference between these two ends of this micro-fluidic chip can form pressure between these two ends of this micro-fluidic chip Difference, this pressure gap can drive sample solution to described end flow;Its function of this miniature ultrasonic transducer units also includes with it The ultrasound wave launched checks its absorption on described inner surface of pipeline of biomacromolecule contained in sample, and then checks this Its body of the substrate of polydimethylsiloxane material is relative to the effect of swallowing up of this biomacromolecule;Described polydimethylsiloxane material Its function of substrate includes and cover plate and working electrode and electrode and reference electrode together build this micro-fluidic chip, and soft also have bullet Its function of substrate of this polydimethylsiloxane material of property also includes, with the character of its absorption strong to ultrasound wave, entering ultrasound wave Row is strong to be absorbed, and thereby realizes ultrasound wave within limited short distance between this terminal of this micro-fluidic chip to this sample introduction end The rapid decrement of intensity.
The easily-disassembled hypotype swine flue multi-channel testing device comprising electromagnetism auxiliary part the most according to claim 1, its Being characterised by, described pipeline and described lateral and described manifold shape turnout are capillary channel.
The easily-disassembled hypotype swine flue multi-channel testing device comprising electromagnetism auxiliary part the most according to claim 1, its Being characterised by, described thermal decomposition conducting polymer is the electric conductivity material formed after anoxybiotic heat treatment by polyimides or polyacrylonitrile Material.
The easily-disassembled hypotype swine flue multi-channel testing device comprising electromagnetism auxiliary part the most according to claim 1, its Be characterised by, the width of described working electrode or diameter between 0.1 micron to 2000 micron, and, described work electricity The length of pole is between 1 micron to 15000 micron.
The easily-disassembled hypotype swine flue multi-channel testing device comprising electromagnetism auxiliary part the most according to claim 1, its Being characterised by, the thickness of described gold size sensitive membrane is between 10 nanometers and 200 nanometers.
The easily-disassembled hypotype swine flue multi-channel testing device comprising electromagnetism auxiliary part the most according to claim 1, its Being characterised by, its material of described cover plate in structure is polydimethylsiloxane material.
The easily-disassembled hypotype swine flue multi-channel testing device comprising electromagnetism auxiliary part the most according to claim 1, its Be characterised by, be positioned at this micro-fluidic chip this sample introduction end these two liquid pools its with to be positioned at this of this this terminal of micro-fluidic chip remaining Under a liquid pool between air line distance between 3 centimetres and 7 centimetres.
The easily-disassembled hypotype swine flue multi-channel testing device comprising electromagnetism auxiliary part the most according to claim 1, its Being characterised by, described cover plate in structure and its thickness of substrate are all between 1.0 millimeters and 5.0 millimeters.
The easily-disassembled hypotype swine flue multi-channel testing device comprising electromagnetism auxiliary part the most according to claim 1, its Being characterised by, the structure of this device also includes higher-order of oscillation electric signal generator, and it is another for described higher-order of oscillation electric signal transmission cable One end is connected with this higher-order of oscillation electric signal generator.
The easily-disassembled hypotype swine flue multi-channel testing device comprising electromagnetism auxiliary part the most according to claim 1, its Being characterised by, its specified ultrasonic emitting power of this miniature ultrasonic transducer units is between 5 milliwatts and 9000 milliwatts, and this is micro- The frequency of its ultrasound wave operationally launched of type ultrasonic transducer is between 100KHz and 12MHz.
CN201510131872.6A 2015-03-18 2015-03-18 Comprise the easily-disassembled hypotype swine flue multi-channel testing device of electromagnetism auxiliary part Pending CN106153890A (en)

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