CN105891472A - Cheap cholera diagnosis micro-fluidic device with specific fluid flow transmission mode - Google Patents
Cheap cholera diagnosis micro-fluidic device with specific fluid flow transmission mode Download PDFInfo
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Abstract
The invention relates to a cheap cholera diagnosis micro-fluidic device with a specific fluid flow transmission mode, and belongs to the field of analytical tests. A series of problems exist if polydimethylsiloxane (PDMS) which is cheap and extremely easy to process is used for manufacturing a substrate of a micro-fluidic chip for cholera diagnosis; the surface of PDMS is highly hydrophobic, and the effect of targeted surface modification is not lasting. The cheap cholera diagnosis micro-fluidic device with the specific fluid flow transmission mode aims at solving the series of related problems. The cheap cholera diagnosis micro-fluidic device with the specific fluid flow transmission mode is characterized in that PDMS with an original surface is selected as the substrate, a micro ultrasonic transducer is attached to the position close to the sample fluid flow terminal of the micro-fluidic chip, and interfacial tension is reduced with ultrasonic waves; meanwhile, the strong absorption capacity of PDMS to ultrasonic waves is utilized for rapidly and gradually reducing the intensity of ultrasonic waves in a short distance, an interfacial tension difference is formed at the two ends of the chip accordingly, a pressure difference is formed between the two ends due to the interfacial tension difference, and sample fluid is driven under the pressure difference to flow towards to the terminal along a capillary pipe.
Description
Technical field
The present invention relates to the cheap cholera diagnosis micro fluidic device that a kind of sap flow process mode is special, belong to analysis field tests.
Background technology
Associated multi-channel micro-fluidic cholera diagnostic techniques background, may refer to CN 200910150930.4 application for a patent for invention case such as grade.
Only for itself overall general picture of microflow control technique, may refer to the monograph " diagram Microfluid based Lab on a chip " that famous micro-fluidic expert Mr. Lin Ping Cheng goes out not long ago, this monograph is published by Science Press, this monograph to past of microflow control technique, now, and, vision of the future etc. aspect, suffers 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, see to be exactly some micro-channel on apparent, after waiting until to cover cover plate thereon, just real Guan Bi forms described small fluid course, and the conduit inner surface of this micro-channel constitutes described small fluid course together with the part cover plate that surround this micro-channel；So, obviously, assembling this small fluid course after completing, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, the state of this micro-channel inner surface or character substantially determine integrality or the character of this small fluid course；Therefore saying, inner surface state or the inner surface character of this structure micro-channel on substrate are key factors；In principle, any material that can keep or substantially keep 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 can be monocrystalline silicon piece, piezoid, sheet glass, high polymer such as polydimethylsiloxane, polymethyl methacrylate, Merlon etc.；Certainly, the selection of substrate can be identical with the selection of cover plate, it is also possible to differs；From the point of view of in terms of material consumption, manufacture difficulty and application popularization prospect etc., between these materials, there is the selection of the least difference, especially that substrate, affect bigger.
In various substrates make material, polydimethylsiloxane, i.e. PDMS, the easiest molding, makes micro-channel extremely simple on such substrate, and this lower cost for material, substrate is made 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, and is a kind of more satisfactory selection seemingly；Certainly, patch material can also select to use cheap polydimethyl siloxane material: so, and this substrate selection is the scheme of polydimethyl siloxane material, and material is extremely cheap, makes extremely simple, seems and should also be as being extremely easy to popularize, promote.
But, thing is really not so simply.
One, this polydimethyl siloxane material, the material that i.e. abbreviation letter PDMS is referred to, it itself it is the most hydrophobic a kind of material, this material builds micro-channel, if not carrying out the modified operation for this micro-channel surface, so, after entirety has been assembled, after i.e. covering cover plate, because its inner surface of described micro-channel in structure occupies the inner surface of most fluid course, so, this its strong hydrophobic property of PDMS micro-channel inner surface, it it is deciding factor, it can make to be similar to the fine liquid stream of polar liquid of aqueous solution by becoming the most difficult, its flow resistance is big, the most general Micropump is all difficult to promote, certainly, if cover plate also selects to use this PDMS material, so, 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, constitute serious technical puzzlement, it is another problem: the internal mutually PDMS polymer molecule of this its body of PDMS material substrate has and automatically diffuses to the surface, the characteristic migrated, this substrate body internal PDMS polymer molecule mutually diffuses to the surface automatically, the characteristic migrated, the sufficiently long time can not be maintained by making the state after the modification of that its inner surface of micro-channel of surface modification modification, holding time of its inner surface state of micro-channel after that is surface-modified has substantially been only sufficient to the time needs of laboratory internal test experiments；In other words, through this PDMS micro-channel inner surface that surface modification or surface are modified, after its modification or say the apparent condition formed after modification can not be lasting, but automatically tend to soon or say the apparent condition become again before surface modification, in relatively short period of time, returning to the most hydrophobic apparent condition of that script, so, justing think, such micro-fluidic chip can make in a large number, mass storage, be widely popularized, and answer is clearly, that is exactly, it is impossible to.Micro-channel on this PDMS material, does not do if surface modifies, and is similar to the fine liquid stream of polar solvent of aqueous solution and cannot pump and pass through, and chip the most just cannot use；And if done surface modification, the state after cannot persistently keeping again it to modify, or equally cannot popularization and application.
So, how to accomplish to utilize cheap PDMS material to make substrate, and can release described micro-channel inner surface decorating state cannot persistently, chip cannot make in a large number, lay in and then be widely popularized such a puzzlement making the numerous professional in this area be entangled with for a long time in a large number, 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.
They are two years old, the PDMS material of non-surface modification, above it is stated that, its surface is the most hydrophobic, the most hydrophobic this material surface and also another problem, that is exactly, biomacromolecule can be adsorbed in the most hydrophobic this PDMS surface, further, the depression that these adsorbed biomacromolecules also can be further on PDMS surface further, gradually falls into the deepest, until within the heavy body phase being trapped in PDMS substrate, in fact, this process, be partly also due to PDMS material body phase interior polymeric thing molecule have diffuse to the surface, travel motion is caused；This situation, can also explain from another angle, i.e., internal to its diffusion into the surface, those polymer molecules of migration mutually by PDMS body continuously, the result of its motion, within being the body phase that those have little by little been involved in PDMS substrate by the biomacromolecule of surface adsorption, briefly, these adsorbed biomacromolecules are swallowed up mutually by PDMS substrate body exactly；So, this PDMS substrate body swallows up the phenomenon of biomacromolecule mutually, and its impact caused necessarily causes 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, constantly it is adsorbed, is 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, another kind of explanation is to say, PDMS body mutually in there is substantial amounts of Minute pores, associated biomolecule macromole is by after surface adsorption, depression enters these Minute pores, and then is swallowed up；But, inventor thinks, those can allow that the air molecule of miniature scale 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 both difference on yardstick are huge, must not make sweeping generalizations.Bypassing explanation, in any case, the biomacromolecule analyzing object as dependence test is adsorbed by PDMS substrate micro-channel inner surface, and then is constantly swallowed up by PDMS substrate body phase, and this is the phenomenon of known objective reality.
In order to stop the effect of swallowing up relative to biomacromolecule of this PDMS substrate body, from containment PDMS surface, the absorption of biomacromolecule can be addressed, way is aiming at this PDMS material surface and is chemically modified modification, from the point of view of when with PDMS as substrate material, it is exactly that the surface to described micro-channel part is chemically modified modification, through the described micro-channel inner surface that chemical modification is modified, its absorption to biomacromolecule can be contained, and then avoid biomacromolecule to be swallowed up by PDMS substrate body phase；But, or that old problem, that is exactly, the apparent condition after chemical modification modification on PDMS material surface cannot persistently keep, its process automatically diffusing to the surface, migrating of polymer molecule that this PDMS substrate body is internal mutually, can be become that again originally the most hydrophobic and state of strong adsorption biomacromolecule soon through the micro-channel inner surface state that surface chemical modification is modified, in other words, no matter how professionals in the field turn from side to side, and its micro-channel inner surface of this PDMS 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, long-term this PDMS substrate micro-channel inner surface absorption process to biomacromolecule of containment can be reached again, and then stop the effect of swallowing up of PDMS substrate body Relative biological macromole, related chip manufactured goods are made to be able to maintain that a shelf-life the most long, rational, it is simply that a difficult problem the most thorny.This difficult problem, as another difficult problem addressed above, makes the numerous professional in this area be entangled with for a long time, perplex equally, and this difficult problem is the highly difficult problem that its obvious technology barrier can not be despised equally.Having there are a lot of days in this difficult problem, up to now, is the most not yet properly settled.
Summary of the invention
The technical problem to be solved is, one package solution is provided, solves two difficult problems addressed above totally, and, this solution is applied to cholera diagnosis multichannel micro-fluidic chip field, forms a kind of novel cholera diagnosis multichannel micro-fluidic device.
nullThe present invention solves described technical problem by following scheme，The device that the program provides is the cheap cholera diagnosis micro fluidic device that a kind of sap flow process mode is special，The structure of this micro fluidic 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 are plate object or tablet，The channel structure formed via mould pressing process or etching technics is contained in that face towards this cover plate of this substrate，This substrate possibly together be connected with this channel structure and pierce this substrate via mould pressing process、The window structure that etching technics or simple drilling technology are formed，This substrate being installed together bonded to each other and this cover plate have been built into jointly 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 the interface zone that this substrate is bonded to each other with this cover plate，Its side of this window is blocked by this cover plate and opposite side is open，The locations of structures of this window is exactly the locations of structures of described liquid pool，The quantity of described liquid pool is three，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，This terminal is located remotely from each other with this sample introduction end，One end of this pipeline via be similarly positioned in the manifold shape turnout of this interface zone bonded to each other respectively with this Liang Ge liquid pool UNICOM being positioned at sample introduction end，This remaining liquid pool UNICOM of the other end of this pipeline and the described terminal being positioned at this micro-fluidic chip，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 made up of conductive electrode and the gold size sensitive membrane having embedded cholera specific antigen that is attached on this conductive electrode，The structure of this pipeline is parallel construction，The described pipeline in parallel construction is made up of four lateral parallel connections，The quantity of described working electrode is four，The installation position of these four working electrodes lays respectively in described four laterals，And，Specific antigen in its top layer gold size sensitive membrane structure of these four working electrodes is four kinds of cholera antigenic substances that can be specific binding to cholera antibody respectively，These four kinds of antigenic substances are cholera TP0821 antigen and cholera TP0319 antigen and cholera TP0624 antigen and cholera O139 antigen respectively，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，Its material of this substrate is polydimethylsiloxane 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 the surface of primary form of this material of any surface chemical modification or any surface chemical modification，The structure of this micro fluidic device also includes miniature ultrasonic transducer units，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 miniature ultrasonic transducer units is installed in the cover plate of this micro-fluidic chip or the position of the neighbouring described terminal of substrate with attaching；Its major function of this miniature ultrasonic transducer units is when the actual sample introduction of micro-fluidic chip is tested, utilize its ultrasound wave launched to reduce the interfacial tension between the inwall of sample solution and described pipeline, can be compatible, and, utilize the distance difference between described sample introduction end and described terminal and this miniature ultrasonic transducer units installation position and the difference on its ultrasonic intensity experienced, difference between its interfacial tension of sample introduction end and its interfacial tension of described terminal described in induced synthesis, interfacial tension difference between these two ends of this micro-fluidic chip can form pressure gap between these two ends of this micro-fluidic chip, this pressure gap can drive sample solution to described end flow；Its function of this miniature ultrasonic transducer units also includes checking its absorption on described inner surface of pipeline of biomacromolecule contained in sample with its ultrasound wave launched, and then checks its body of the substrate effect of swallowing up relative to this biomacromolecule of this polydimethylsiloxane material；Its function of substrate of described polydimethylsiloxane material includes and cover plate and working electrode and electrode and reference electrode are together built this micro-fluidic chip, soft and this polydimethylsiloxane material of having elasticity its function of substrate also includes with the character of its absorption strong to ultrasound wave, ultrasound wave is absorbed strongly, and thereby realizes the rapid decrement of ultrasonic intensity within limited short distance between this terminal of this micro-fluidic chip to this sample introduction end.
Described gold size sensitive membrane is to be sufficiently mixed uniformly by chitosan gold size solution and cholera specific antigen solution, with point sample instrument point sample or coat specified structure position, and makes its drying and forming-film form.Cholera specific antigen in described gold size sensitive membrane is the cholera antigen of horseradish peroxidase or glucose oxidase labelling, described gold size sensitive membrane has been included as fixing above-mentioned each cholera specific antigen and has introduced complementary medium therein, and described complementary medium 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 size 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, the passage of capillary level the most all selected by described pipeline and described lateral and described manifold shape turnout, and the passage of described capillary level implies that the passage that its internal diameter is suitable with the internal diameter of the capillary tube on ordinary meaning.The shape of cross section of described its inner passage of capillary tube can be arbitrary shape, described shape of cross section is the most circular, oval, square, rectangle, bar shaped, can certainly be the linear of arbitrary existence 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 selected shape, described arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..Described is known to itself the art-recognized meanings of vocabulary of electrode and described reference electrode.
This case microfluidic chip structure relates to several liquid pools, described liquid pool is the pond shape for transitional liquid storage or scrotiform structure, 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 the hypomegetic liquid pool mated with capillary tube.
Only for itself the art-recognized meanings of the ultrasonic transducer one word professional for ultrasonic technology field, it is known.
Various sizes, variously-shaped ultrasonic transducer are commercially available；Its size of commercially available miniature ultrasonic transducer units may diminish to the magnitude only calculated with millimeter.
For itself, for the professional in ultrasonic technology field, it is only known general technology with regard to its technique for fixing on general industry application solid body surface of miniature ultrasonic transducer units.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；Similarly, 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 micro fluidic device can also include higher-order of oscillation electric signal generator；The described higher-order of oscillation its other end of electric signal transmission cable 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, is 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 is between 2 milliwatts and 2000 milliwatts；The preferred scope of the frequency of its ultrasound wave operationally launched of this miniature ultrasonic transducer units is between 100KHz and 12MHz.
This case device can further include some adnexaes certainly, and described adnexa such as multiple tracks electrochemical workstation etc., the art-recognized meanings of described 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 couple via the most special the corresponding interface got lines crossed with described multiple tracks electrochemical workstation respectively.The described special private cable being used to that each the corresponding interface of each described electrode Yu described multiple tracks electrochemical workstation is carried out to be coupled to each other of getting lines crossed.Described micro-fluidic chip in this case device, its structure can also include that micro-valve, the quantity of described micro-valve do not limit, according to actual needs, 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 itself manufacturing technology and use technology be 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 allow the length being easily installed use being arbitrarily set, it is however recommended to or to say preferred its scope of described length be between 1 micron to 15000 micron.
The described gold size sensitive membrane of described working electrode surface layer it is installed in by spraying or point sample instrument point sample or the coating of other appropriate process, its thicknesses of layers can allow the thickness that the sample measuring liquid the treated generation electrical signals being arbitrarily set responds, it is however recommended to thickness in other words conj.or perhaps preferably thickness be 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, polymethyl methacrylate, polydimethylsiloxane, etc., in order to make smaller size of micro-fluidic chip, such as make the micro-fluidic chip of the super-small of length only 2.0 centimetres to 3.0 centimetres, and in the distance that this is extremely short, realize the extremely fast decay to ultrasound wave, 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.
These two liquid pools itself and the air line distance between this remaining liquid pool of this this terminal of micro-fluidic chip at this sample introduction end of this micro-fluidic chip 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 to say preferred 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:
Proposing first based on this case and this first public novel liquid stream driving principle, among its application running of this case micro-fluidic chip, 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, drive liquid stream to flow in the capillary channel of this four-way micro-fluidic chip, utilize four-way electrochemical analytical instrument respectively four kinds of cholera antibody to be detected.
Detect corresponding four kinds of cholera antibody with four kinds of cholera antigens, detect corresponding four kinds of cholera antigens with four kinds of cholera antibody, similarly, can cholera diagnosis；The principle of its foundation is, necessarily antigen, antibody deposit in cholera patient, and mutually Reversible binding, form reversible conjugate, therefore, detect antibody thereby cholera diagnosis with antigen, go to detect antigen cholera diagnosis with antibody, diagnostic purpose can be reached.Certainly, its corresponding electrode sensitive decorative layer of different means technically and differs.
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 cholera antibody molecules are captured by the cholera specific antigen of the corresponding horseradish peroxidase-labeled of gold size sensitive membrane embedding on electrode surface in each passage.
2, the cholera specific antigen of horseradish peroxidase-labeled forms immune complex with the cholera antibody in blood serum sample.
3, use multi-channel electrochemical analyzer, add the electron mediators such as catechol, the curent change using the above-mentioned reaction of amperometric detection to cause, it is derived from kind and the content of various analyte.
4, result is comprehensively analyzed, cholera antibody is carried out comprehensive diagnos.
It is an advantage of the invention that, its close position of described terminal at described micro-fluidic chip installs miniature ultrasonic transducer units with attaching, utilize its low-power launched of this miniature ultrasonic transducer units, the ultrasound wave of high-frequency band, make this most hydrophobic its tube wall of micro-fluidic chip internal pipeline without surface chemical modification and test object water solution between the compatibility be significantly increased, this for sample liquid stream by providing a realistic possibility；Simultaneously, utilize its strong absorbability to ultrasound wave of polydimethylsiloxane substrate, in comparatively short distance, namely, in the shortest distance of the only several centimeters yardstick from described terminal to described sample introduction end, reach the rapid decrement of ultrasonic intensity, thereby the difference of described interfacial tension is caused at the described two ends at this micro-fluidic chip, and then, utilize the pressure gap between its these two ends formed of difference of the interfacial tension between these two ends, drive 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 surface chemical modification or chemical modification, altogether dispense with the laborious procedures of this surface chemical modification or chemical modification；And altogether dispense with the equipment of traditional Micropump etc；On the other hand, this low-power, the ultrasound wave of high-frequency band, the absorption on this literalness naked its inner surface of pipeline of polydimethylsiloxane substrate of the biomacromolecule in sample can also be contained, and then contain the effect of swallowing up of this polydimethylsiloxane substrate the most described biomacromolecule of its body；The Reversible binding thing of described antigen, antibody and antigen and antibody is the most all belonging to the type of described biomacromolecule；Owing to described adsorption and the described effect of swallowing up are contained effectively, therefore, dependence test result will be better able to reflect practical situation objectively；This low-power, the effect of high-frequency band ultrasound wave, the most also include facilitating what the Reversible binding between antigen, antibody reacted quickly to reach, and this makes the dependence 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 operation, therefore, this surface chemical modification layer or chemically modified 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 its damaging influence to described surface chemical modification layer or chemically modified layer caused and do not exist.
The technical scheme of this case has dissolved a series of technical barriers relevant to its application of polydimethylsiloxane substrate addressed above totally.Based on this case scheme, the polydimethyl siloxane material that this kind is the most cheap is the most likely prepared at this micro-fluidic chip, is produced, application etc. field plays bigger effect.
Accompanying drawing explanation
Fig. 1 is the schematic diagram of this micro fluidic device embodiment chip part of this case structure, shown be this example structure depression angle under chip internal pipeline and each electrode and the configuration of each relevant liquid pool, this figure is not depicted described miniature ultrasonic transducer units and other described adnexa.
Fig. 2 is its rough outside side view of this micro fluidic device of this case.
nullIn figure，1、2、10 is the liquid pool that three installation positions are different respectively，3 is manifold shape turnout，4、7、11、14 are installation position difference but four laterals forming UNICOM in parallel structure parallel with one another respectively，5 is the working electrode that specific antigenic substance is cholera TP0821 antigen in its top layer gold size sensitive membrane structure being installed in lateral 4，6 is the working electrode that specific antigenic substance is cholera TP0319 antigen in its top layer gold size sensitive membrane structure being installed in lateral 7，12 is the working electrode that specific antigenic substance is cholera TP0624 antigen in its top layer gold size sensitive membrane structure being installed in lateral 11，13 is the working electrode that specific antigenic substance is cholera O139 antigen in its top layer gold size sensitive membrane structure being installed in lateral 14，8 is to electrode，9 is reference electrode，15 is the substrate of polydimethylsiloxane material，16 is cover plate，17 is higher-order of oscillation electric signal transmission cable，18 is miniature ultrasonic transducer units，19 is the described sample introduction end of this micro-fluidic chip，20 is the described terminal of this micro-fluidic chip；Arrow in legend indicate this micro-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
nullIn this embodiment of this case that Fig. 1 and Fig. 2 is shown，The structure of this micro fluidic device includes multichannel micro-fluidic chip，The structure of this micro-fluidic chip includes bonded to each other being installed in substrate 15 together and cover plate 16，Described substrate 15 and cover plate 16 are plate object or tablet，The channel structure formed via mould pressing process or etching technics is contained in that face towards this cover plate 16 of this substrate 15，This substrate 15 possibly together be connected with this channel structure and pierce this substrate via mould pressing process、The window structure that etching technics or simple drilling technology are formed，This substrate 15 being installed together bonded to each other and this cover plate 16 have been built into jointly containing pipeline configuration and the micro-fluidic chip of liquid pool structure that is attached thereto，Described liquid pool is liquid pool 1、Liquid pool 2、Liquid pool 10，The locations of structures of this pipeline is positioned at the interface zone that this substrate 15 is bonded to each other with this cover plate 16，Its side of this window is blocked by this cover plate 16 and opposite side is open，The locations of structures of this window is exactly described liquid pool 1、Liquid pool 2、The locations of structures of liquid pool 10，The quantity of described liquid pool is three，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 end 19 of this micro-fluidic chip，The terminal 20 of its chip liquid flowing when a remaining liquid pool i.e. its locations of structures of liquid pool 10 is positioned at the test of this micro-fluidic chip actual sample introduction，This terminal 20 is located remotely from each other with this sample introduction end 19，One end of this pipeline via be similarly positioned in the manifold shape turnout 3 of this interface zone bonded to each other respectively with this liquid pool 1 and this liquid pool 2 UNICOM being positioned at sample introduction end 19，This remaining liquid pool i.e. liquid pool 10 UNICOM of the other end of this pipeline and the described terminal 20 being positioned at this micro-fluidic chip，And，The working electrode that is sequentially respectively installed in this pipeline on diverse location and to electrode 8 and reference electrode 9，Described working electrode is made up of conductive electrode and the gold size sensitive membrane having embedded cholera specific antigen that is attached on this conductive electrode，The structure of this pipeline is parallel construction，The described pipeline in parallel construction is made up of four lateral parallel connections，The quantity of described working electrode is four，The installation position of these four working electrodes lays respectively in described four laterals，These four working electrodes are working electrode 5 respectively、Working electrode 6、Working electrode 12、Working electrode 13，And，Specific antigen in its top layer gold size sensitive membrane structure of these four working electrodes is four kinds of cholera antigenic substances that can be specific binding to cholera antibody respectively，These four kinds of antigenic substances are cholera TP0821 antigen and cholera TP0319 antigen and cholera TP0624 antigen and cholera O139 antigen respectively，From the point of view of specifically launching，5 is the working electrode that specific antigenic substance is cholera TP0821 antigen in its top layer gold size sensitive membrane structure being installed in lateral 4，6 is the working electrode that specific antigenic substance is cholera TP0319 antigen in its top layer gold size sensitive membrane structure being installed in lateral 7，12 is the working electrode that specific antigenic substance is cholera TP0624 antigen in its top layer gold size sensitive membrane structure being installed in lateral 11，13 is the working electrode that specific antigenic substance is cholera O139 antigen in its top layer gold size sensitive membrane structure being installed in lateral 14，Described working electrode 5、Working electrode 6、Working electrode 12、Its material of working electrode 13 is gold material or thermal decomposition conducting polymer material，Described working electrode 5、Working electrode 6、Working electrode 12、Its pattern of working electrode 13 presents lamellar or thread，It is important that，This its material of substrate 15 is polydimethylsiloxane material，This its surface of substrate 15 is the surface of primary form，The surface of this primary form its be intended to refer to not through the surface of primary form of this material of any surface chemical modification or any surface chemical modification，The structure of this micro fluidic device also includes miniature ultrasonic transducer units 18，And，Higher-order of oscillation electric signal transmission cable 17，One end of this higher-order of oscillation electric signal transmission cable 17 links together with this miniature ultrasonic transducer units 18，This miniature ultrasonic transducer units 18 is installed in the cover plate 16 of this micro-fluidic chip or the position of the neighbouring described terminal 20 of substrate 15 with attaching；This its major function of miniature ultrasonic transducer units 18 is when the actual sample introduction of micro-fluidic chip is tested, utilize its ultrasound wave launched to reduce the interfacial tension between the inwall of sample solution and described pipeline, can be compatible, and, utilize the distance difference between described sample introduction end 19 and described terminal 20 and this miniature ultrasonic transducer units 18 installation position and the difference on its ultrasonic intensity experienced, difference between its interfacial tension of sample introduction end 19 and its interfacial tension of described terminal 20 described in induced synthesis, these two ends of this micro-fluidic chip i.e. interfacial tension difference between sample introduction end 19 and terminal 20 i.e. can form pressure gap at these two ends of this micro-fluidic chip between sample introduction end 19 and terminal 20, this pressure gap can drive sample solution to flow to described terminal 20 direction；This its function of miniature ultrasonic transducer units 18 also includes checking its absorption on described inner surface of pipeline of biomacromolecule contained in sample with its ultrasound wave launched, and then checks its body of substrate 15 effect of swallowing up relative to this biomacromolecule of this polydimethylsiloxane material；Its function of substrate 15 of described polydimethylsiloxane material includes and cover plate 16 and working electrode 5, working electrode 6, working electrode 12, working electrode 13 and electrode 8 and reference electrode 9 are together built this micro-fluidic chip, soft and this polydimethylsiloxane material of having elasticity its function of substrate also includes with the character of its absorption strong to ultrasound wave, ultrasound wave is absorbed strongly, and thereby realizes the rapid decrement of ultrasonic intensity within limited short distance between this terminal of this micro-fluidic chip to this sample introduction end.
Arrow in legend indicate this micro-fluidic chip its when actual motion, driven by pressure at two ends difference, the flow direction of its sample liquid stream.
Fig. 1 is depicted without miniature ultrasonic transducer units 18 and higher-order of oscillation electric signal transmission cable 17；Further, Fig. 1 and Fig. 2 is all depicted without the associate members such as described higher-order of oscillation electric signal generator and multiple tracks electrochemical workstation.
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 17 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 to electrode and reference electrode can respectively via the most special cable or say 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.
This case device is to detect multiple corresponding cholera antibody, thereby cholera diagnosis with multiple cholera antigen.
Claims (10)
- null1. the cheap cholera diagnosis micro fluidic device that sap flow process mode is special，The structure of this micro fluidic 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 are plate object or tablet，The channel structure formed via mould pressing process or etching technics is contained in that face towards this cover plate of this substrate，This substrate possibly together be connected with this channel structure and pierce this substrate via mould pressing process、The window structure that etching technics or simple drilling technology are formed，This substrate being installed together bonded to each other and this cover plate have been built into jointly 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 the interface zone that this substrate is bonded to each other with this cover plate，Its side of this window is blocked by this cover plate and opposite side is open，The locations of structures of this window is exactly the locations of structures of described liquid pool，The quantity of described liquid pool is three，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，This terminal is located remotely from each other with this sample introduction end，One end of this pipeline via be similarly positioned in the manifold shape turnout of this interface zone bonded to each other respectively with this Liang Ge liquid pool UNICOM being positioned at sample introduction end，This remaining liquid pool UNICOM of the other end of this pipeline and the described terminal being positioned at this micro-fluidic chip，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 made up of conductive electrode and the gold size sensitive membrane having embedded cholera specific antibody that is attached on this conductive electrode，The structure of this pipeline is parallel construction，The described pipeline in parallel construction is made up of four lateral parallel connections，The quantity of described working electrode is four，The installation position of these four working electrodes lays respectively in described four laterals，And，Specific antigen in its top layer gold size sensitive membrane structure of these four working electrodes is four kinds of cholera antigenic substances that can be specific binding to cholera antibody respectively，These four kinds of antigenic substances are cholera TP0821 antigen and cholera TP0319 antigen and cholera TP0624 antigen and cholera O139 antigen respectively，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 characterized in that，Its material of this substrate is polydimethylsiloxane 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 the surface of primary form of this material of any surface chemical modification or any surface chemical modification，The structure of this micro fluidic device also includes miniature ultrasonic transducer units，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 miniature ultrasonic transducer units is installed in the cover plate of this micro-fluidic chip or the position of the neighbouring described terminal of substrate with attaching；Its major function of this miniature ultrasonic transducer units is when the actual sample introduction of micro-fluidic chip is tested, utilize its ultrasound wave launched to reduce the interfacial tension between the inwall of sample solution and described pipeline, can be compatible, and, utilize the distance difference between described sample introduction end and described terminal and this miniature ultrasonic transducer units installation position and the difference on its ultrasonic intensity experienced, difference between its interfacial tension of sample introduction end and its interfacial tension of described terminal described in induced synthesis, interfacial tension difference between these two ends of this micro-fluidic chip can form pressure gap between these two ends of this micro-fluidic chip, this pressure gap can drive sample solution to described end flow；Its function of this miniature ultrasonic transducer units also includes checking its absorption on described inner surface of pipeline of biomacromolecule contained in sample with its ultrasound wave launched, and then checks its body of the substrate effect of swallowing up relative to this biomacromolecule of this polydimethylsiloxane material；Its function of substrate of described polydimethylsiloxane material includes and cover plate and working electrode and electrode and reference electrode are together built this micro-fluidic chip, soft and this polydimethylsiloxane material of having elasticity its function of substrate also includes with the character of its absorption strong to ultrasound wave, ultrasound wave is absorbed strongly, and thereby realizes the rapid decrement of ultrasonic intensity within limited short distance between this terminal of this micro-fluidic chip to this sample introduction end.
- The cheap cholera diagnosis micro fluidic device that sap flow process mode the most according to claim 1 is special, it is characterised in that described pipeline and described lateral and described manifold shape turnout are capillary channel.
- The cheap cholera diagnosis micro fluidic device that sap flow process mode the most according to claim 1 is special, it is characterised in that described thermal decomposition conducting polymer is the conductive material formed after anoxybiotic heat treatment by polyimides or polyacrylonitrile.
- The cheap cholera diagnosis micro fluidic device that sap flow process mode the most according to claim 1 is special, it is characterized in that, the width of described working electrode or diameter between 0.1 micron to 2000 micron, and, the length of described working electrode is between 1 micron to 15000 micron.
- The cheap cholera diagnosis micro fluidic device that sap flow process mode the most according to claim 1 is special, it is characterised in that the thickness of described gold size sensitive membrane is between 10 nanometers and 200 nanometers.
- The cheap cholera diagnosis micro fluidic device that sap flow process mode the most according to claim 1 is special, it is characterised in that its material of described cover plate in structure is polydimethylsiloxane material.
- The cheap cholera diagnosis micro fluidic device that sap flow process mode the most according to claim 1 is special, it is characterized in that, in these two liquid pools itself and the air line distance between this remaining liquid pool of this this terminal of micro-fluidic chip of this sample introduction end of this micro-fluidic chip between 3 centimetres and 7 centimetres.
- The cheap cholera diagnosis micro fluidic device that sap flow process mode the most according to claim 1 is special, it is characterised in that described cover plate in structure and its thickness of substrate are all between 1.0 millimeters and 5.0 millimeters.
- The cheap cholera diagnosis micro fluidic device that sap flow process mode the most according to claim 1 is special, it is characterized in that, the structure of this micro fluidic device also includes that higher-order of oscillation electric signal generator, the described higher-order of oscillation its other end of electric signal transmission cable are connected with this higher-order of oscillation electric signal generator.
- The cheap cholera diagnosis micro fluidic device that sap flow process mode the most according to claim 1 is special, it is characterized in that, its specified ultrasonic emitting power of this miniature ultrasonic transducer units is between 2 milliwatts and 2000 milliwatts, and the frequency of its ultrasound wave operationally launched of this miniature ultrasonic transducer units is between 100KHz and 12MHz.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN201348632Y (en) * | 2008-12-30 | 2009-11-18 | 宁波大学 | Special micro-fluidic chip for diagnosing cholera |
| CN101587123A (en) * | 2009-06-19 | 2009-11-25 | 宁波大学 | Special micro-fluidic chip for cholera diagnosis with one-dimensional self-assembly magnetic bead chain electrodes |
| CN102645429A (en) * | 2012-04-23 | 2012-08-22 | 宁波大学 | Self-cleaning and vibration wave energy digestion link containing electrogenerated chemiluminescence analyzing and detecting device |
-
2015
- 2015-01-18 CN CN201510036683.0A patent/CN105891472A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN201348632Y (en) * | 2008-12-30 | 2009-11-18 | 宁波大学 | Special micro-fluidic chip for diagnosing cholera |
| CN101587123A (en) * | 2009-06-19 | 2009-11-25 | 宁波大学 | Special micro-fluidic chip for cholera diagnosis with one-dimensional self-assembly magnetic bead chain electrodes |
| CN102645429A (en) * | 2012-04-23 | 2012-08-22 | 宁波大学 | Self-cleaning and vibration wave energy digestion link containing electrogenerated chemiluminescence analyzing and detecting device |
Non-Patent Citations (1)
| Title |
|---|
| JAMES FRIEND: "Microscale acoustofluidics: microfluidics driven via acoustics and ultrasonics", 《REVIEWS OF MODERN PHYSICS》 * |
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Application publication date: 20160824 |