CN106290930A - The hypotype swine flue multi-channel testing device of the Dual Drive coupling containing hydrophobic substrate - Google Patents
The hypotype swine flue multi-channel testing device of the Dual Drive coupling containing hydrophobic substrate Download PDFInfo
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- CN106290930A CN106290930A CN201510300319.0A CN201510300319A CN106290930A CN 106290930 A CN106290930 A CN 106290930A CN 201510300319 A CN201510300319 A CN 201510300319A CN 106290930 A CN106290930 A CN 106290930A
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Abstract
The present invention relates to the hypotype swine flue multi-channel testing device of a kind of Dual Drive containing hydrophobic substrate coupling, 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;This case is for this series difficult problem.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 interfacial tension difference is formed at the two ends of this chip, this difference provides a kind of and drives the strength that sample liquid stream flows to this terminal direction along hydrophobic capillary channel, this strength and simultaneously with its mechanicalness of Micropump pumping strength Collaboration of comprising in structure.
Description
Technical field
The present invention relates to a kind of Dual Drive containing hydrophobic substrate coupling hypotype swine flue multi-channel testing device, this device be based on
Antigen/antibody specific reaction diagnoses the special purpose device of hypotype swine flue antigen, belongs 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.
Its three, as it has been described above, this PDMS micro-channel inner surface is the most hydrophobic, and surface chemical modification targetedly or come to the surface
Learning to modify is difficult to again persistently, therefore, actual can only still belong to the shortest in the apparent condition after its surface modification or surface are modified
It is used within phase;If have passed through that ofer short duration expiry date, and if using by force, due to surface shape
State, the most again near hydrophobic state, uses usual Micropump to drive sample liquid stream then to certainly exist bigger flow resistance,
So, just test liquid can only be forced to flow to target direction flowing by strengthening Micropump pump power and pumping pressure, as it has been described above,
This PDMS material is soft, pumps sample liquid stream with pumping pressure too high, machinery, and it enters will to cause this substrate
Sample end include sample introduction end near zone described micro-channel generation bubbling, expanded, distort, deform, and, this high-pressure situations
Under, it is in this sample introduction end and the micro-channel of near zone thereof and periphery is also susceptible to the stripping between substrate and cover plate, these feelings
Under shape, sample solution will enter the crack of the appearance between substrate and the cover plate formed after described stripping and flow over everywhere, and this is real
Border causes the damage of this micro-fluidic chip;Certainly, if this surface modification or surface are modified the most not in place, also result in
Within of short duration usual effect duration, said circumstances occurs;In the case of the additional Micropump of simple employing carries out liquid stream driving, above-mentioned
This problem exists all the time.If as it has been described above, entirely without doing the pre actions such as any described surface modification or surface modification,
So, this problem above-mentioned by even more serious, even without occur micro-channel bubbling described in sample introduction end and near zone thereof, expanded,
Distortion, the problem such as stripping between deformation and substrate and cover plate, merely because this flow resistance is excessive, use high pressure Micropump the most not
Sample liquid stream must be driven to march forward towards terminal side.
Summary of the invention
The technical problem to be solved is to provide a package solution, solves three addressed above simultaneously
The a series of difficult problem the most mutually involved together of aspect, and, this solution is applied to the diagnosis of hypotype swine flue
Use multichannel micro-fluidic chip field, form a kind of 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 a kind of to drive containing the double of hydrophobic substrate
The hypotype swine flue multi-channel testing device of dynamic coupling, the structure of this device includes multichannel micro-fluidic chip, this micro-fluidic chip
Structure include bonded to each other being installed in substrate together and cover plate, described substrate and cover plate are plate object or tablet, this base
The channel structure formed via mould pressing process or etching technics is contained in that face towards this cover plate of sheet, bonded to each other is arranged on one
This substrate risen and this cover plate have been built into the micro-fluidic chip containing pipeline configuration jointly, and the locations of structures of this pipeline is positioned at this base
The juncture area that sheet is bonded to each other with this cover plate, the two ends of this pipeline are respectively with the sample introduction end of this micro-fluidic chip and terminal even
Connecing, this sample introduction end is the injection end of this micro-fluidic chip sample solution, this terminal be this micro-fluidic chip actual sample introduction test time its
The terminal of sample solution flowing in chip, this terminal is located remotely from each other with this sample introduction end, and the distance between this terminal and this sample introduction end is situated between
Between 3 centimetres and 10 centimetres, in this pipeline, on diverse location, sequentially it is equiped with working electrode and to electrode and reference
Electrode, described working electrode is resisted by conductive electrode and the hypotype swine flue specificity that embedded that is attached on this conductive electrode
The gold size sensitive membrane of body is constituted, and the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is by three laterals also
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 branched pipes
In road, and, the specific antibody in its top layer gold size sensitive membrane structure of these three working electrodes is to resist hypotype swine flue respectively
Three kinds of hypotype swine flue antibody materials that proper energy is specific binding, these three kinds of antibody materials are hypotype swine flue specific antibody respectively
H1N1、H3N2And H1N2, its material of described working electrode is gold material or thermal decomposition conducting polymer material, described working electrode
Its pattern presents lamellar or thread, it is important that, its material of this substrate is polydimethylsiloxane material, and its surface of this substrate is former
The surface of raw form, the surface of this primary form its be intended to refer to not through any surface chemical modification or any surface chemistry
The surface of the primary form of this modified material, the structure of this device also includes chain ring type magnetic holding device, this chain ring type magnetic holding device
Its structure has six links, described link all in strip, shaft-like or bar-shaped, each adjacent link is hinged formation 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 is hinged knot
Structure position, this hexagonal annular structure two its materials of link being in opposite side position therein are magnetic conductivity materials, this hexagon
Its material of remaining four processes of circulus is all non-magnetic material, and described non magnetic material refers to externally-applied magnetic field the strongest
The material of strong response, a link among two links of this magnetic conductivity material is wound with magnet exciting coil, and this is wound with excitation
The link of coil is respectively equiped with the pole shoe of a magnetic conductivity material in the both sides neighbor positions of its magnet exciting coil, has described in two
Pole shoe, these 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 is pasted
The attached fixing miniature ultrasonic transducer units that is equiped with, this chain ring type magnetic holding device socket of support electromagnetism adhesive strength is positioned at this miniflow
The close position of control its described terminal of chip, and, higher-order of oscillation electric signal transmission cable, this higher-order of oscillation electric signal transmission electricity
One end of cable links together with this miniature ultrasonic transducer units;This chain ring type magnetic holding device provides one and facilitates this device to disassemble
Function;Its major function of this miniature ultrasonic transducer units is when the actual sample introduction of micro-fluidic chip is tested, and utilizes it to be launched
Ultrasound wave reduces the interfacial tension between the inwall of sample solution and this its inner passage of micro-fluidic chip so that it is can be compatible,
Further, utilize the distance difference between described sample introduction end and described terminal and this miniature ultrasonic transducer units installation position and its
The difference on ultrasonic intensity experienced, its interfacial tension of sample introduction end described in induced synthesis and its interfacial tension of described terminal it
Between 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
Power difference, this pressure gap can drive sample solution to described end flow;Its function of this miniature ultrasonic transducer units also include with
Its ultrasound wave launched check in sample contained biomacromolecule its on its inner passage inner surface of this micro-fluidic chip
Absorption, and then check its body of the substrate effect of swallowing up relative to this biomacromolecule of this polydimethylsiloxane material;Softness is also
Its function of substrate of this polydimethylsiloxane material that tool is elastic includes with the character of its absorption strong to ultrasound wave, to ultrasound wave
Strongly absorb, and thereby realize within limited short distance between this terminal of this micro-fluidic chip to this sample introduction end ultrasonic
The rapid decrement of intensity of wave;And, Micropump, this Micropump is connected with this sample introduction end;The function of this Micropump is, at this sample solution
And the interfacial tension between the inwall of this its inner passage of micro-fluidic chip is reduced by this ul-trasonic irradiation, the alternate compatibility increases
Precondition under, pump, with the mechanicalness of this Micropump, the interfacial tension that strength comes between the described two ends of this ultrasound wave induction poor
Its driving force brought different is supported mutually, adjusts mutually, is mutually coupled, and pools one and drive in the way of Collaboration
Test liquid flows to the strength of described terminal direction flowing.
Itself art-recognized meanings of described Micropump one word is known for the professional in micro-fluidic chip field.
The most miniature piezoelectric pump of described Micropump, miniature peristaltic pump, miniature air driven pump, etc..
Described Micropump both can be with the Micropump being external form;This Micropump can also be to do into or say inside this micro-fluidic chip of embedding
The Micropump of the built in version of its sample introduction end structure position or this sample introduction end Near-neighbor Structure position.
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 includes described lateral, and its internal diameter size may each be arbitrarily selected
Size, but, for as far as possible less with liquid sample to be measured and the consideration that reduces the aspects such as reagent loss, described in described pipeline includes
Lateral the most all selects the passage of capillary level, the passage of described capillary level to imply that its internal diameter and the capillary on ordinary meaning
The passage that the internal diameter of pipe is suitable.The shape of cross section of described its inner passage of capillary tube can be arbitrary shape, described cross section
Shape is the most circular, oval, square, rectangle, bar shaped, naturally it is also possible to be arbitrary to there is the linear of bending, and,
The interior shape of described capillary tube is along with the extension of pipeline, and the shape of cross section of different parts 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.
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.
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.
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:
This case drives liquid stream to flow in the capillary channel of this triple channel micro-fluidic chip with described Dual Drive coupling operating mode,
Multi-channel electrochemical analyzer device is utilized respectively three kinds of hypotype swine flue diagnostic antigens to be detected.
The concrete detection of this case micro-fluidic chip uses step as follows:
1, in micro-pipeline, blood serum sample liquid is added, under described Dual Drive coupling operating mode drives, various hypotype swine flue
Antigen molecule is flowed by the hypotype pig of the corresponding horseradish peroxidase-labeled of gold size sensitive membrane embedding on electrode surface in each passage
Sense specific antibody 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
Stating the difference of interfacial tension, the difference of the interfacial tension between these two ends can cause a kind of driving force, and this kind is poor because of interfacial tension
Its function of driving force that is different and that cause is to drive sample liquid stream in the most hydrophobic capillary channel to described terminal side
To flowing;And simultaneous described Micropump in structure, its function is, this sample solution and this micro-fluidic chip inside it logical
Under the precondition that interfacial tension between the inwall in road is reduced by this ul-trasonic irradiation, the alternate compatibility increases, with this Micropump
Mechanicalness pumping strength come and this ultrasound wave induction described two ends between its driving force brought of interfacial tension difference
Support mutually, adjust mutually, be mutually coupled, in the way of Collaboration, pool one drive test liquid to flow to described terminal side
Strength to flowing;The existence of this Micropump so that its ultrasonic emitting intensity of this miniature ultrasonic transducer units can be allowed to appropriateness
Reducing, this is particularly suitable for for the situation containing ultrasound wave sensitive composition in detection object;And due to this ultrasonic transducer and
The existence of radiated ultrasound wave, it is possible to increase the alternate compatibility, reduce interfacial tension, and provide this two ends interfacial tension difference its
The special driving force brought, then, in this case, its flow resistance in this micro-channel of sample liquid stream significantly drops
Low, correspondingly, its running resistance of this Micropump is greatly reduced, and so, this Micropump just can be to carry out than relatively low pumping pressure
For the pumping work of described sample solution, owing to mechanical pumping pressure is greatly reduced, therefore, in such a situation,
Just it is not susceptible to the described micro-channel drum of described sample introduction end and the near zone thereof caused because sample introduction terminal tool pumping pressure is excessive
Steep, expand, deform, distort and stripping etc. problem between this region substrate and cover plate;The coupling running of this Dual Drive of this case
Scheme and add for this sample fluid flow action handling, it is possible to allow to use ultrasonic intensity, ultrasonic frequency,
Micropump pump power, Micropump pumping pressure etc. multiple indexs include flowing forward for flow rate, the flowing action of this flowing
Dynamic or time-out flowing or acceleration flowing etc. flowing action carries out multiparameter and accurately manipulates;By the coupling running of this Dual Drive of this case
Scheme, entirely without its micro-channel of substrate of this polydimethylsiloxane material etc. relevant surfaces being carried out any surface chemistry
Modify or surface chemical modification, altogether dispensed with the laborious procedures of this surface chemical modification or surface chemical modification;On the other hand,
This low-power, the ultrasound wave of high-frequency band, additionally it is possible to the biomacromolecule in containment sample is at this literalness naked poly dimethyl
Absorption on its inner surface of pipeline of siloxanes substrate, and then contain that this polydimethylsiloxane substrate the most described biology of its body divides greatly
The effect of swallowing up of son;Described antigen, antibody and antigen and the Reversible binding thing of antibody are the most all belonging to described biological big point
The type of son;Owing to described adsorption and the described effect of swallowing up are contained effectively, therefore, dependence test result will
It is better able to reflect objectively practical situation;This low-power, the effect of high-frequency band ultrasound wave, the most also include facilitating antigen,
Quickly reaching of Reversible binding reaction between antibody, this makes dependence test operate can be to complete than speed faster.
As it has been described above, the existence of this Micropump so that its ultrasonic emitting intensity of this miniature ultrasonic transducer units can be allowed to fit
Degree reduces, then, this feature contributes to protecting its sensitive coating of described working electrode, is allowed to from ultrasound injury.
Based on this case scheme, completely without carrying out repairing for the surface chemistry of this polydimethylsiloxane its relevant surfaces of substrate
Decorations or surface chemical modification operation, therefore, this surface chemical modification layer or surface chemical modification layer not need to exist,
So, its body phase interior polymeric thing molecule of this polydimethylsiloxane substrate the most automatically diffuses to the surface, migrates what it was caused
The damaging influence of described surface chemical modification layer or surface chemical modification layer is not existed.
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, this kind the most inexpensively and easily polydimethyl siloxane material of processing and fabricating just has can
Can at this micro-fluidic chip, it be prepared, produces, 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
This miniature ultrasonic transducer units attached in magnetic link just can be mutually disengaged with this micro-fluidic chip easily, then, should
The component that part can freely depart from just can be reused many times with circulating benignly;This architectural feature is conducive to saving this device
Use cost.
Accompanying drawing explanation
Fig. 1 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. 2 is the outside side view under another viewing angle of this device of this case;The viewing angle of Fig. 2 and the sight of Fig. 1
Examine angle to be mutually perpendicular to;Fig. 2 is depicted without the component such as infusion tube and Micropump.
In figure, 1 is chain ring type magnetic holding device, and 2 is the described terminal of this micro-fluidic chip, and 3 is the described of this micro-fluidic chip
Sample introduction end, 4 is the substrate of polydimethylsiloxane material, and 5 is cover plate, and 6 is miniature ultrasonic transducer units, and 7 is high frequency vibrating
Swinging electric signal transmission cable, 8,15 are in the link of two magnetic conductivity materials of different structure position respectively, these two magnetic conductions
The link end-to-end relation the most each other of property material, 9,22 are in two pole shoes of different structure position respectively, 10,
12,14,17,19,21 six pin joints being in six diverse locations respectively, 11,13,18,20 is place respectively
In the link of four non magnetic materials of four diverse locations, 16 is magnet exciting coil, and 23 is infusion tube, and 24 is Micropump;Figure
This chain ring type magnetic holding device structure in example is only the legend structure of signal, and this chain ring type magnetic holding device structure actual is not limited to this figure
Example chain ring type magnetic holding device structure;Arrow in legend indicate this micro-fluidic chip its when actual motion, by pressure at two ends
Difference drives, the flow direction of its sample liquid stream.
Detailed description of the invention
In this embodiment of this case that Fig. 1 and Fig. 2 is shown, the structure of this device includes multichannel micro-fluidic chip, and this is micro-
The structure of fluidic chip includes bonded to each other being installed in substrate 4 together and cover plate 5, and described substrate 4 and cover plate 5 are tabular
Thing or tablet, the conduit knot formed via mould pressing process or etching technics is contained in that face towards this cover plate 5 of this substrate 4
Structure, this substrate 4 being installed together bonded to each other has been built into the micro-fluidic chip containing pipeline configuration jointly with this cover plate 5,
The locations of structures of this pipeline is positioned at the juncture area that this substrate 4 is bonded to each other with this cover plate 5, and the two ends of this pipeline are micro-with this respectively
Sample introduction end 3 and the terminal 2 of fluidic chip connect, and this sample introduction end 3 is the injection end of this micro-fluidic chip sample solution, and this is eventually
The terminal of sample solution flowing in its chip, this terminal 2 and this sample introduction end 3 when end 2 is the test of this micro-fluidic chip actual sample introduction
Being located remotely from each other, the distance between this terminal 2 and this sample introduction end 3 is between 3 centimetres and 10 centimetres, different in this pipeline
Sequentially being equiped with working electrode on position and to electrode and reference electrode, described working electrode is by conductive electrode and attaching
The gold size sensitive membrane having embedded hypotype swine flue specific antibody on this conductive electrode is constituted, and the structure of this pipeline is parallel connection
Structure, the described pipeline in parallel construction is made up of three lateral parallel connections, and the quantity of described working electrode is three, and these are three years old
The installation position of individual working electrode lays respectively in described three laterals, and, this its top layer gold size of three working electrodes is quick
Specific antibody in sense membrane structure is three kinds of hypotype swine flue antibody things that can be specific binding to hypotype swine flue antigen respectively
Matter, these three kinds of antibody materials are hypotype swine flue specific antibody H respectively1N1、H3N2And H1N2, its material of described working electrode is
Gold material or thermal decomposition conducting polymer material, its pattern of described working electrode presents lamellar or thread, it is important that, this substrate
4 its materials are polydimethylsiloxane materials, and this its surface of substrate 4 is the surface of primary form, the surface of this primary form its
It is intended to refer to not through the surface of primary form of this material of any surface chemical modification or any surface chemical modification, should
The structure of device also includes chain ring type magnetic holding device 1, this its structure of chain ring type magnetic holding device 1 has six links 8,11,
13,15,18,20, described link 8,11,13,15,18,20 all in strip, shaft-like or bar-shaped, each adjacent link
Be hinged formation chain link, the hexagonal circulus of its appearance profile of this chain link, each drift angle of this hexagonal annular structure
10,12,14,17,19,21 its locations of structures are articulated structure position, at two therein of this hexagonal annular structure
Its material of link 8,15 in opposite side position is magnetic conductivity material, the remaining four processes of this hexagonal annular structure 11,13,
18,20 its materials are all non-magnetic material, and described non magnetic material refers to the material the most strongly responded externally-applied magnetic field,
Being wound with magnet exciting coil 16 in a link 15 among two links of this magnetic conductivity material, this is wound with magnet exciting coil 16
Link 15 in the both sides neighbor positions of its magnet exciting coil 16, be respectively equiped with the pole shoe of a magnetic conductivity material, have two
Described pole shoe 9,22, these two pole shoes 9,22 are directed to the link 8 of another magnetic conductivity material, this another magnetic conductivity material
The fixing miniature ultrasonic transducer units 6 that is equiped with is attached, this chain ring type electricity of support electromagnetism adhesive strength on its surface of link 8 of matter
Magnetic holding device 1 socket is positioned at the close position of its described terminal 2 of this micro-fluidic chip, and, higher-order of oscillation electric signal transmission electricity
Cable 7, one end of this higher-order of oscillation electric signal transmission cable 7 links together with this miniature ultrasonic transducer units 6;This chain ring type
Magnetic holding device 1 provides a function facilitating this device to disassemble;This its major function of miniature ultrasonic transducer units 6 is at miniflow
During control chip actual sample introduction test, utilize its ultrasound wave launched to reduce sample solution and its inner passage of this micro-fluidic chip
Inwall between interfacial tension so that it is can be compatible, and, utilize described sample introduction end 3 and described terminal 2 miniature with this
Distance difference between ultrasonic transducer 6 installation position and the difference on its ultrasonic intensity experienced, induced synthesis
Difference between described its interfacial tension of sample introduction end 3 and its interfacial tension of described terminal 2, these two ends 2,3 of this micro-fluidic chip
Between interfacial tension difference can form pressure gap between these two ends 2,3 of this micro-fluidic chip, this pressure gap can drive
Dynamic sample solution flows to described terminal 2 direction;This its function of miniature ultrasonic transducer units 6 also include with its launched ultrasonic
Ripple checks its absorption on its inner passage inner surface of this micro-fluidic chip of biomacromolecule contained in sample, and then checks
Its body of substrate 4 of this polydimethylsiloxane material is relative to the effect of swallowing up of this biomacromolecule;Soft and have elasticity this poly-two
Its function of substrate 4 of methylsiloxane material includes, with the character of its absorption strong to ultrasound wave, strongly inhaling ultrasound wave
Receive, and thereby realize ultrasonic intensity within limited short distance between this terminal 2 of this micro-fluidic chip to this sample introduction end 3
Rapid decrement;And, Micropump 24, this Micropump 24 is connected with this sample introduction end 3;The function of this Micropump 24 is, in this examination
Interfacial tension between the inwall of sample solution and this its inner passage of micro-fluidic chip reduced by this ul-trasonic irradiation, alternate compatible
Property the precondition that increases under, pump strength with the mechanicalness of this Micropump 24 and come and the described two ends 2,3 of this ultrasound wave induction
Between its driving force brought of interfacial tension difference support mutually, adjust mutually, be mutually coupled, with the side of Collaboration
Formula pools one and drives test liquid to flow to the strength of described terminal 2 direction flowing.
Arrow in legend indicate this micro-fluidic chip its when actual motion, driven by two ends 2,3 pressure differential, its examination
The flow direction of sample liquid stream.
Fig. 1 and Fig. 2 is all depicted without the associate members such as described higher-order of oscillation electric signal generator.
Involved magnetic conductive material and involved nonmagnetic substance market are the most on sale.
Involved miniature ultrasonic transducer units 6 is commercially available;Can also customize to ultrasonic transducer producer.
Described Micropump 24 can customize to specialized factory.
Involved higher-order of oscillation electric signal transmission cable 7 is commercially available;Can also be to ultrasonic transducer producer or cable special manufacturer
Family's customization.
Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available;Can also customize to relevant manufacturers
Involved its inner passage of this micro-fluidic chip of this case is the pipeline of hydrophobic capillary tube form.
Itself art-recognized meanings of described Micropump one word is known for the professional in micro-fluidic chip field.
The most miniature piezoelectric pump of described Micropump, miniature peristaltic pump, miniature air driven pump, etc..
Described Micropump both can be with the Micropump being external form;This Micropump can also be to do into or say inside this micro-fluidic chip of embedding
The Micropump of the built in version of its sample introduction end structure position or this sample introduction end Near-neighbor Structure position.Micropump in legend is external form
Micropump;This Micropump can certainly do into or say the embedding internal sample introduction end of this microfluidic chip structure or its Near-neighbor Structure position
The Micropump of described built in version, its basic structure key element is identical with the Micropump of external form.
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 in legend is only an example, the knot of chain ring type magnetic holding device described in this case
Configuration state is not limited to the version in this legend.
Claims (10)
1. the hypotype swine flue multi-channel testing device of the Dual Drive coupling containing hydrophobic substrate, the structure of this device includes that multichannel is micro-
Fluidic chip, the structure of this micro-fluidic chip includes bonded to each other being installed in substrate together and cover plate, and described substrate and cover plate are equal
For plate object or tablet, the conduit formed via mould pressing process or etching technics is contained in that face towards this cover plate of this substrate
Structure, this substrate being installed together bonded to each other and this cover plate have jointly been built into the micro-fluidic chip containing pipeline configuration, have been somebody's turn to do
The locations of structures of pipeline is positioned at the juncture area that this substrate is bonded to each other with this cover plate, the two ends of this pipeline respectively with this micro-fluidic core
The sample introduction end of sheet and terminal connect, and this sample introduction end is the injection end of this micro-fluidic chip sample solution, and this terminal is that this is micro-fluidic
Chip actual sample introduction test time its chip in sample solution flowing terminal, this terminal is located remotely from each other with this sample introduction end, this terminal and
Distance between this sample introduction end, between 3 centimetres and 10 centimetres, is sequentially equiped with work electricity in this pipeline on diverse location
Pole and to electrode and reference electrode, described working electrode is by conductive electrode and is attached to the embedding on this conductive electrode
The gold size sensitive membrane of hypotype swine flue specific antibody is constituted, the structure of this pipeline is parallel construction, described in parallel construction
Pipeline is made up of three lateral parallel connections, and the quantity of described working electrode is three, and the installation position of these three working electrodes divides
It is not positioned at described three laterals, and, the specific antibody in its top layer gold size sensitive membrane structure of these three working electrodes
Being the three kind hypotype swine flue antibody materials specific binding to hypotype swine flue antigen energy respectively, these three kinds of antibody materials are respectively
Hypotype swine flue specific antibody H1N1、H3N2And H1N2, its material of described working electrode is gold material or thermal decomposition conductive polymer
Sub-material, its pattern of described working electrode presents lamellar or thread, it is characterised in that its material of this substrate is polydimethylsiloxanes
Alkane material, its surface of this substrate is the surface of primary form, the surface of this primary form its be intended to refer to not through any table
The surface of the primary form of this material of face chemical modification or any surface chemical modification, the structure of this device also includes chain ring type electricity
Magnetic holding device, has six links in this its structure of chain ring type magnetic holding device, described link all in strip, shaft-like or bar-shaped, each phase
Adjacent link is hinged formation chain link, the hexagonal circulus of its appearance profile of this chain link, this hexagonal annular structure each
Its locations of structures of drift angle is articulated structure position, this hexagonal annular structure two its materials of link being in opposite side position therein
Matter is magnetic conductivity material, and its material of remaining four processes of this hexagonal annular structure is all non-magnetic material, described non magnetic material
Matter refers to the material the most strongly responded externally-applied magnetic field, and a link among two links of this magnetic conductivity material is wound around
Having magnet exciting coil, this is wound with the link of magnet exciting coil and is respectively equiped with a magnetic conductivity in the both sides neighbor positions of its magnet exciting coil
The pole shoe of material, has two described pole shoes, and these two pole shoes are directed to the link of another magnetic conductivity material, this another lead
The fixing miniature ultrasonic transducer units that is equiped with, this chain ring type of support electromagnetism adhesive strength is attached on its surface of the link of magnetic material
Magnetic holding device socket is positioned at the close position of its described terminal of this micro-fluidic chip, and, higher-order of oscillation electric signal transmission cable,
One end of this higher-order of oscillation electric signal transmission cable links together with this miniature ultrasonic transducer units;This chain ring type magnetic holding device carries
Supply a function facilitating this device to disassemble;Its major function of this miniature ultrasonic transducer units is at the actual sample introduction of micro-fluidic chip
During test, utilize its ultrasound wave launched to reduce the boundary between the inwall of sample solution and this its inner passage of micro-fluidic chip
Surface tension so that it is can be compatible, and, utilize described sample introduction end and described terminal to install position with this miniature ultrasonic transducer units
Distance difference between putting and the difference on its ultrasonic intensity experienced, its interfacial tension of sample introduction end described in induced synthesis
And the difference between its interfacial tension of described terminal, the interfacial tension difference between these two ends of this micro-fluidic chip can be micro-fluidic at this
Forming pressure gap between these two ends of chip, this pressure gap can drive sample solution to described end flow;This miniature ultrasonic
Its function of wave transducer also includes checking biomacromolecule contained in sample with its ultrasound wave launched, and it is micro-fluidic at this
Absorption on its inner passage inner surface of chip, and then its body of substrate checking this polydimethylsiloxane material is big relative to this biology
The effect of swallowing up of molecule;Soft and this polydimethylsiloxane material of having elasticity its function of substrate includes with it strong to ultrasound wave
The character of strong absorption, absorbs strongly to ultrasound wave, and thereby having between this terminal of this micro-fluidic chip to this sample introduction end
The rapid decrement of ultrasonic intensity is realized within the short distance of limit;And, Micropump, this Micropump is connected with this sample introduction end;This Micropump
Function be that the interfacial tension between the inwall of this sample solution and this its inner passage of micro-fluidic chip is by this ul-trasonic irradiation
And reduce, under precondition that the alternate compatibility increases, pump strength with the mechanicalness of this Micropump and come and the institute of this ultrasound wave induction
State its driving force brought of the interfacial tension difference between two ends to support mutually, adjust mutually, be mutually coupled, with collaborative fortune
The mode made pools one and drives test liquid to flow to the strength of described terminal direction flowing.
The hypotype swine flue multi-channel testing device of the Dual Drive coupling containing hydrophobic substrate the most according to claim 1, it is special
Levying and be, described pipeline includes that described lateral is capillary channel.
The hypotype swine flue multi-channel testing device of the Dual Drive coupling containing hydrophobic substrate the most according to claim 1, it is special
Levying and be, described thermal decomposition conducting polymer is the electric conductivity material formed after anoxybiotic heat treatment by polyimides or polyacrylonitrile
Material.
The hypotype swine flue multi-channel testing device of the Dual Drive coupling containing hydrophobic substrate the most according to claim 1, it is special
Levy and be, the width of described working electrode or diameter between 0.1 micron to 2000 micron, and, described working electrode
Length between 1 micron to 15000 micron.
The hypotype swine flue multi-channel testing device of the Dual Drive coupling containing hydrophobic substrate the most according to claim 1, it is special
Levying and be, the thickness of described gold size sensitive membrane is between 10 nanometers and 200 nanometers.
The hypotype swine flue multi-channel testing device of the Dual Drive coupling containing hydrophobic substrate the most according to claim 1, it is special
Levying and be, its material of described cover plate in structure is polydimethylsiloxane material.
The hypotype swine flue multi-channel testing device of the Dual Drive coupling containing hydrophobic substrate the most according to claim 1, it is special
Levying and be, described Micropump is miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.
The hypotype swine flue multi-channel testing device of the Dual Drive coupling containing hydrophobic substrate the most according to claim 1, it is special
Levying and be, described cover plate in structure and its thickness of substrate are all between 1.0 millimeters and 5.0 millimeters.
The hypotype swine flue multi-channel testing device of the Dual Drive coupling containing hydrophobic substrate the most according to claim 1, it is special
Levying and be, the structure of this device also includes higher-order of oscillation electric signal generator, described higher-order of oscillation electric signal transmission cable its another
End is connected with this higher-order of oscillation electric signal generator.
The hypotype swine flue multi-channel testing device of the Dual Drive coupling containing hydrophobic substrate the most according to claim 1, it is special
Levying and be, its specified ultrasonic emitting power of this miniature ultrasonic transducer units is between 5 milliwatts and 9000 milliwatts, and this is miniature
The frequency of its ultrasound wave operationally launched of ultrasonic transducer is between 100KHz and 12MHz.
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