CN107649202A - The easily-disassembled cholera diagnosis device of liquid stream driving is carried out by means of interfacial characteristics - Google Patents
The easily-disassembled cholera diagnosis device of liquid stream driving is carried out by means of interfacial characteristics Download PDFInfo
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Abstract
The present invention relates to a kind of easily-disassembled cholera diagnosis device that liquid stream driving is carried out by means of interfacial characteristics, belong to analysis testing field.Serial problem be present with dimethyl silicone polymer i.e. PDMS that is cheap and easily processing come the substrate for making cholera diagnosis micro-fluidic chip；Its surface of the PDMS material is strongly hydrophobic, and targetedly surface is modified or surface modification, its effect are difficult to persistently, and this case aims to solve the problem that the serial relevant issues.This case main points are, the selected PDMS with ecosystem surface of substrate, and by the elastic clip that miniature ultrasonic transducer units are attached on its clamping limb with elastic force snap-in location in its neighbor positions of the sample liquid stream terminal of the micro-fluidic chip, interfacial tension is reduced with ultrasonic wave, strong absorbability using PDMS to ultrasonic wave simultaneously, reach ultrasonic intensity rapid decrement in short distance, so as to form interfacial tension difference at the both ends of the chip, sample liquid stream is thereby facilitated to be flowed along capillary channel to the terminal direction.
Description
Technical field
The present invention relates to a kind of easily-disassembled cholera diagnosis device that liquid stream driving is carried out by means of interfacial characteristics, the dress
Put is to belong to analysis testing field based on antigen/antibody specific reaction come the special purpose device of cholera diagnosis antigen.
Background technology
The micro-fluidic cholera diagnostic techniques background of associated multi-channel, may refer to the patents of invention such as CN 200910150930.4
Application case.
Only for the microflow control technique overall general picture of itself, famous micro-fluidic expert Mr. Lin Ping Cheng may refer to not
The monograph " diagram Microfluid based Lab on a chip " gone out before long, the monograph is published via Science Press, and the monograph is to micro-fluidic
Past of technology, now, and, vision of the future etc. etc., suffer from detail, be deep into long discussion of detail.
So, the Important Problems of this case that to have a talk below concern.
The basic framework of micro-fluidic chip, including be etched with the substrate of small fluid course and fit together therewith
Cover plate, the small fluid course on the substrate, before upper cover plate is assembled, it is apparent on see to be exactly some micro-channels, to wait until
After covering cover plate thereon, just really closure forms the small fluid course, the conduit inner surface of the micro-channel together with
The part cover plate that surround the micro-channel forms described small fluid course together；So, it is clear that after assembling completes
The small fluid course, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, should
The state or property of micro-channel inner surface substantially determine the integrality or property of the small fluid course；Therefore say, this
The inner surface state or inner surface property of micro-channel of the individual structure on substrate are key factors；In principle, it is any can
The material of its solid forms is kept or kept substantially, can be used to make substrate and cover plate, such as, it can act as substrate and lid
The material of piece can be monocrystalline silicon piece, quartz plate, sheet glass, high polymer for example dimethyl silicone polymer, polymethyl methacrylate,
Makrolon etc.；Certainly, the selection of substrate and the selection of cover plate be able to can also be differed with identical；From material consumption, make
From the point of view of difficulty and application popularization prospect etc. etc., not small difference, the especially choosing of that substrate between these materials be present
Material, have a great influence.
In various substrate making materials, dimethyl silicone polymer, i.e. PDMS, comparatively very easily shaping, at this
It is extremely simple that micro-channel is made on the substrate of sample, and the lower cost for material, base is made with the polydimethyl siloxane material
Piece, micro-channel, and the cover plate phase made with the cheap material such as glass or polypropylene or other plastic sheets are being suppressed or etched thereon
Coordinate, be a kind of more satisfactory selection seemingly；Certainly, patch material can also select to use cheap dimethyl silicone polymer
Material：So, this substrate selection is the scheme of polydimethyl siloxane material, and material is extremely cheap, and making is extremely simple, seems
It should be extremely easy to popularize, promote.
But thing is really not so simple.
First, this polydimethyl siloxane material, that is, the material that alphabetical PDMS is referred to of abridging, itself are a kind of strong
Strong hydrophobic material, micro-channel is built on this material, if without being operated for the modified of the micro-channel surface, that
, after overall assembling is completed, that is, after covering cover plate, because the micro-channel its inner surface in structure occupies most liquid
The inner surface of circulation road, then, its strong hydrophobic property of the PDMS micro-channels inner surface, is deciding factor, it can cause
Similar to the aqueous solution the fine liquid stream of polar liquid by becoming very difficult, its flow resistance is big, or even in general is micro-
Pump is all difficult to promote, certainly, if cover plate also selects to use the PDMS material, then, problem is substantially identical, similar；
Therefore, among prior art, modification is modified particular for the micro-channel inner surface on the PDMS material, is necessary behaviour
Make；So, this is pretty troublesome for the modified operation of PDMS micro-channel inner surfacesThat falls nor this problem, is formed tight
Weight technology puzzlement, be another problem：PDMS polymer molecules inside its body phase of this PDMS material substrate have automatic
The characteristic diffuse to the surface, migrated, the spy that this substrate body phase inside PDMS polymer molecules are diffused to the surface, migrated automatically
Property, the state after modification by its inner surface of that micro-channel of surface modifying and decorating will be caused can not to maintain long enough
Time, the holding time for micro-channel its inner surface state after that is surface-modified be substantially only sufficient to complete laboratory internal
The time of test experiments needs；In other words, by surface modification or the PDMS micro-channel inner surfaces of surface modification, it is modified
The surface state that is formed can not be lasting afterwards or after saying modification, but soon automatically tends to or say and become surface modification again
Surface state before, the strong hydrophobic surface state of that script is returned in the shorter time, then, just think, this
The micro-fluidic chip of sample can largely make, mass storage, be widely popularized, and answer is it is obvious that is, impossible.This
Micro-channel on PDMS material, if not doing surface modification, similar to the aqueous solution the fine liquid stream of polar solvent can not pump it is logical
Cross, chip also cannot just use；And if having done surface modification, its state after modifying can not be persistently kept again, or together
Sample can not popularization and application.
So, how to accomplish that substrate can either be made using cheap PDMS material, and the microflute can be released
Road inner surface decorating state can not persistently, chip can not largely make, largely lay in and then be widely popularized and such a make ability
The puzzlement that the numerous professionals in domain are entangled with for a long time, the highly difficult problem that exactly one its obvious technology barrier can not despise.
Be present many year in the highly difficult problem, so far, not yet properly settled.
Second, the PDMS material of non-surface modification, it is stated that, its surface is strongly hydrophobic above, this strong hydrophobic
Material surface and also have another problem, that is, this strong hydrophobic PDMS surfaces can adsorb large biological molecule, and
And these adsorbed large biological molecules can also further depression further on PDMS surfaces, gradually fall into it is gradually deep, until
It is heavy to be trapped within the body phase of PDMS substrates, in fact, this process, partly it is also due to PDMS material body phase interior polymer
Molecule, which has, to be diffused to the surface, caused by travel motion；Such case, it can also be explained from another angle, i.e. continue not
Disconnectedly from inside PDMS body phases to those polymer molecules of its diffusion into the surface, migration, its result moved, be little by little by that
It has been involved in a bit by the large biological molecule of adsorption within the body phase of PDMS substrates, briefly, these adsorbed biologies
Macromolecular is exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up the phenomenon of large biological molecule, its institute
Caused by influence, necessarily cause the severe deviations of all kinds of test data of experiment for being related to large biological molecule.
As described above, the problem of PDMS substrates, is, its not only adsorption large biological molecule, and swallow up biological big point
Son, so, as the large biological molecule of experiment test object, its disappearance will not stop because surface saturation is adsorbed, and
It is, it is constantly adsorbed, also constantly swallowed up.
On PDMS substrates, its body phase is constantly swallowed up and tests showing for associated biomolecule macromolecular in related experiment test process
As, it is to say that another kind, which is explained, substantial amounts of Minute pores in PDMS body phases be present, associated biomolecule macromolecular by after adsorption,
Depression enters these Minute pores, and then is swallowed up；However, inventor thinks, those can allow the sky of miniature scale
Qi leel squeezes into the Minute pores therebetween, not equal to saying that they also can directly allow the large biological molecule of relative large scale to enter
Enter, both difference on yardstick are huge, must not make sweeping generalizations.Explanation is bypassed, in any case, as dependence test analysis object
Large biological molecule is adsorbed by PDMS substrate micro-channels inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is person in charge of reception at ceremonies
Phenomenon existing for sight.
, can be from containment PDMS surfaces pair in order to prevent swallow up effect of this PDMS substrate bodies relative to large biological molecule
The absorption of large biological molecule addresses, and method is chemically modified modification aiming at the PDMS material surface, for
For PDMS is the situation of substrate material, modification exactly is chemically modified to the surface of described micro-channel part, by changing
The micro-channel inner surface of modification is learned, its absorption to large biological molecule can be contained, and then avoid large biological molecule
Swallowed up by PDMS substrate body phases；But or that old problem, that is, the chemical modification on PDMS material surface is modified
Surface state afterwards can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface, move automatically
The process of shifting, it soon can become that micro-channel inner surface state being modified by surface chemical modification again script strong and dredge
Water and the state of strong adsorption large biological molecule, in other words, no matter how professionals in the field turn from side to side, the PDMS bases
Its micro-channel inner surface of piece is always rapidly to strong hydrophobic surface state evolution.
So, how can either obtain that PDMS material price is extremely cheap, substrate makes extremely easy benefit, and can is enough
Reach and contain the absorption process of the PDMS substrate micro-channel inner surfaces to large biological molecule for a long time, and then prevent PDMS substrate body phases
The effect of swallowing up to large biological molecule so that related chip manufactured goods be able to maintain that one it is prolonged enough, reasonably guarantee the quality
Phase, it is exactly a very intractable problem.The problem equally makes this area numerous as another problem addressed above
Professional is entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise.
Also be present many year in the problem, so far, also not yet properly settled.
The content of the invention
The technical problem to be solved by the invention is to provide a package solution, solves totally above
Two problems addressed, also, the solution is applied to cholera diagnosis multichannel micro-fluidic chip field, formed a kind of
New cholera diagnosis Multichannel device.
The present invention solves the technical problem by following scheme, and the device that the program provides is a kind of special by means of interface
Property carry out the easily-disassembled cholera diagnosis device of liquid stream driving, the structure of the device includes multichannel micro-fluidic chip, and this is micro-
The structure of fluidic chip includes being bonded to each other the substrate and cover plate of installing together, and the substrate and cover plate are plate object or piece
The channel structure via mould pressing process or etching technics formation, the base are contained in shape thing, that face towards the cover plate of the substrate
Piece also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or simple drilling technology shape
Into window structure, be bonded to each other the substrate that is installed together and the cover plate be built into jointly containing pipeline configuration and with
Connected liquid pool structure micro-fluidic chip, the locations of structures of the pipeline be located at the interface that the substrate and the cover plate are bonded to each other
Region, its side of the window is blocked by the cover plate and opposite side opens, and the locations of structures of the window is exactly the structure of the liquid pool
Position, the quantity of the liquid pool is three, and its locations of structures of two liquid pools therein is located at the sample introduction end of the micro-fluidic chip, remaining
Under the liquid flowing in its chip when being located at the actual sample introduction test of the micro-fluidic chip of liquid pool its locations of structures terminal, should
Terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is branched off via the manifold shape for being similarly positioned in the interface zone being bonded to each other
Road respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline with positioned at the micro-fluidic chip the terminal
A remaining liquid pool UNICOM, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and right
Electrode and reference electrode, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded cholera
The gold size sensitive membrane of specific antibody is formed, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by four
Lateral is in parallel to be formed, and the quantity of the working electrode is four, and the installation position of four working electrodes is located at institute respectively
State in four laterals, and, the specific antibody in its top layer gold size sensitivity membrane structure of four working electrodes is respectively
The four kinds of cholera antibody materials that can be specifically bound to cholera antigen, four kinds of antibody materials be cholera TP0821 antibody respectively with
And cholera TP0319 antibody and cholera TP0624 antibody and cholera O139 mycoprotein antibody, its material of the working electrode
It is gold material or thermal decomposition conducting polymer material, sheet or thread is presented in its pattern of the working electrode, and emphasis is the base
Its material of piece is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, the surface of the primary form its
The surface of the primary form for the material for not passing through any surface chemical modification or any surface chemical modification is intended to refer to,
The structure of the device also includes elastic clip, the neighbour of two opposite clamping limb snap-in locations of the elastic clip in the micro-fluidic chip
The position of the nearly terminal, fixation is attached on a clamping limb at least in and is equiped with miniature ultrasonic transducer units,
And higher-order of oscillation electric signal transmission cable, one end of the higher-order of oscillation electric signal transmission cable and the miniature ultrasonic transducing
Device links together；The elastic clip provides a function of facilitating the device to disassemble；Its is main for the miniature ultrasonic transducer units
Function is in the test of micro-fluidic chip actual sample introduction, and the ultrasonic wave launched using it reduces sample solution and the pipeline
Inwall between interfacial tension, can be compatible, also, utilize the sample introduction end and the terminal and the miniature ultrasonic
Difference in the distance between wave transducer installation position difference and its ultrasonic intensity experienced, described in induced synthesis
Difference between its interfacial tension of sample introduction end and the terminal its interfacial tension, the interface between the micro-fluidic chip both ends
Power difference can form pressure gap between the both ends of the micro-fluidic chip, and the pressure gap can drive sample solution to described
End flow；The ultrasonic wave that its function of the miniature ultrasonic transducer units also includes being launched with it checks life contained in sample
Its absorption on the inner surface of pipeline of thing macromolecular, and then check the substrate of the dimethyl silicone polymer material its body phase pair
The effect of swallowing up of the large biological molecule；Its function of the substrate of the dimethyl silicone polymer material includes and cover plate and working electrode
And the micro-fluidic chip is together built to electrode and reference electrode, the base of the dimethyl silicone polymer material that is soft and having elasticity
Its function of piece is also included with its property to the strong absorption of ultrasonic wave, and ultrasonic wave is absorbed strongly, and thereby in the miniflow
Control chip terminal is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end, its structure bit
During setting in the test of the micro-fluidic chip actual sample introduction in its chip the terminal of liquid flowing a remaining liquid pool
Claim terminal liquid pool, is filled with some high hydroscopic resin particles in the terminal liquid pool, its opening end of the terminal liquid pool is by breathable microporous
Film is covered.
Described miniature ultrasonic transducer units can certainly be all installed on two clamping limbs；But only install one
Miniature ultrasonic transducer units are dealt with and used enough.
The word of elastic clip one art-recognized meanings of itself are known.
The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and cholera specific antibody solution uniformly, is used a little
Sample instrument point sample is coated on specified structure position, and forms its drying and forming-film.Cholera specificity in the gold size sensitive membrane
Antibody is the cholera antibody of horseradish peroxidase or glucose oxidase mark, and the gold size sensitive membrane has been included as solid
Determine above-mentioned each cholera specific antibody and introduce complementary medium therein, the complementary medium such as chitosan, acetic acid are fine
Dimension is plain, gelatin is therein a kind of or their mixture.
The pipeline and the lateral and the manifold shape turnout in the microfluidic chip structure, in it
Footpath size may each be arbitrarily selected size, still, for as far as possible less with prepare liquid sample and reduction reagent loss etc.
Consideration, the pipeline and the lateral and the manifold shape turnout preferably select capillary level passage, institute
The passage for stating capillary level implies that its internal diameter passage suitable with the internal diameter of the capillary on ordinary meaning.The capillary is in it
The shape of cross section of portion's passage can be arbitrary shape, and the shape of cross section is for example circular, oval, square, rectangle, bar
Shape, naturally it is also possible to it is the linear of bending arbitrarily be present, also, the interior shape of the capillary is with the extension of pipeline,
The shape of cross section of different parts can also allow to be different shapes.Only for the word of capillary one, its art-recognized meanings is public
Know.
What is be related in structure is the electrode of microsize to electrode and reference electrode, and its electrode shape, which may each be, appoints
The selected shape of meaning, the arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..It is described
Art-recognized meanings to electrode and the reference electrode vocabulary of itself are known.
It is related to several liquid pools in this case microfluidic chip structure, the liquid pool is the pond shape or capsule for transitional liquid storage
Shape constructs, and its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, and the cavity shape is for example round
Cylindrical cavity shape, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..The size of the liquid pool can be any
Selected size, still, in order to as far as possible less with prepare liquid sample and reduce reagent loss, the liquid pool be preferably capable of with
The liquid pool of the microminiature of capillary matching.
Only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field,
It is known.
Various sizes, variously-shaped ultrasonic transducer are commercially available；Its size of commercially available miniature ultrasonic transducer units
It may diminish to the magnitude only calculated with millimeter.
Only with regard to miniature ultrasonic transducer units its technique for fixing on general industry application solid body surface its
It is known general technology for the professional in ultrasonic technology field for body.This case is not to this expansion superfluous words.
Only with regard to naked PDMS substrates itself micro-channel molding or lithographic technique for, be open-and-shut known skill
Art；Similarly, the technology of hole-opening is even more known simple technique on naked PDMS substrates.This case is not also superfluous to this expansion
Speech.
The industrial products market of involved its all size of higher-order of oscillation electric signal transmission cable is on sale.
The structure of the device can also include higher-order of oscillation electric signal generator；The higher-order of oscillation electric signal transmission cable
Its other end can be connected with the higher-order of oscillation electric signal generator.
The involved higher-order of oscillation electric signal generator technology of itself, come for the professional in ultrasonic technology field
Say, be simple and known；The higher-order of oscillation electric signal generator can customize to ultrasonic instrument specialized factory.
The preferred scope of its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 5 milliwatts and 5000 milliwatts
Between；The preferred scope of the frequency of its ultrasonic wave operationally launched of the miniature ultrasonic transducer units be between 100KHz with
Between 12MHz.
Only for the word of high hydroscopic resin one art-recognized meanings of itself, come for the professional of chemical field
Say, be known.
The high hydroscopic resin is commercially available.
Only for the word of breathable microporous film one art-recognized meanings of itself, for the professional of technical field of membrane,
It is known.
The breathable microporous film is commercially available.
This case device can further include some annexes certainly, and the annex is such as multiple tracks electrochemical workstation
Deng the art-recognized meanings of the multiple tracks electrochemical workstation are known.The each work being related in this case microfluidic chip structure
Electrode and to electrode and reference electrode etc., special it can get lines crossed and the multiple tracks electrochemical workstation via corresponding respectively
The corresponding interface coupled.It is described that special to get lines crossed be for by each phase of each electrode and the multiple tracks electrochemical workstation
Answer the private cable that interface is coupled to each other.The micro-fluidic chip in this case device, its structure can also include micro-valve,
The quantity of the micro-valve is unlimited, and according to being actually needed, the micro-valve can be installed in any need in the microfluidic chip structure
Position to be mounted；The word of micro-valve one is for the professional of micro fluidic chip technical field, the art-recognized meanings of itself
It is known；The micro-valve itself manufacturing technology and the use of technology is also known；The component that the micro-valve is not required.
The diameter of the working electrode can allow to be that any setting is easily installed the suitable diameter used, still,
It is recommending or say preferable its scope of the diameter between 0.1 micron to 2000 microns；The length of the working electrode can
To allow to be that any setting is easily installed the length used, it is however recommended to or to say the preferable length its scope be 1
Micron is between 15000 microns.
It is installed in by spraying or point sample instrument point sample or the coating of other appropriate process described in the working electrode surface layer
Gold size sensitive membrane, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness,
It is however recommended to thickness preferable thickness is between 10 nanometers and 200 nanometers in other words.
The cover plate in chip structure, its material can allow to be any electrical insulating property material, such as：Polypropylene,
Glass, polymethyl methacrylate, dimethyl silicone polymer, etc., in order to make smaller size of micro-fluidic chip, for example do
Into the micro-fluidic chip of only 2.0 centimetres to 3.0 centimetres of super-small of length, and realized in the extremely short distance to ultrasonic wave
Extremely fast decay, can preferably dimethyl silicone polymer be used as cover plate.Certainly, selected on large-sized micro-fluidic chip
Using dimethyl silicone polymer it is used as the cover plate, and this case technical scheme is allowed.
Positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal should
Air line distance between a remaining liquid pool can be arbitrarily selected suitable distance, still, the distance as needed
Preferred value is between 3 centimetres and 7 centimetres.
Described its thickness of cover plate and substrate can allow be any setting the thickness for being easy to assembling, the thickness of recommendation or say
Preferable thickness is between 1.0 millimeters and 5.0 millimeters.Less thickness is advantageous to save material.
The application method of this case micro-fluidic chip：
Itd is proposed first based on this case and the first public new liquid stream driving principle, its application of this case micro-fluidic chip are transported
Among work, the new liquid stream driving method is determined completely without involving any additional Micropump.
The interfacial tension difference that this case is formed between micro-fluidic chip both ends caused by the ultrasonic wave,
Driving liquid stream flows in the capillary channel of the four-way micro-fluidic chip, right respectively using four-way electrochemical analytical instrument
Four kinds of cholera diagnostic antigens are detected.
The specific detection of this case micro-fluidic chip is as follows using step：
1st, blood serum sample liquid is added in micro-pipe road, under ultrasonic wave driving, various cholera antigen molecules are by each logical
The cholera specific antibody for the corresponding horseradish peroxidase-labeled that gold size sensitive membrane embeds captures on electrode surface in road.
2nd, the cholera specific antibody of horseradish peroxidase-labeled is formed immune multiple with the cholera antigen in blood serum sample
Compound.
3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, it is above-mentioned using amperometric detection
Curent change caused by reaction, it is derived from the species and content of various analytes.
4th, result is subjected to comprehensive analysis, comprehensive diagnos is carried out to cholera antigen.
It is an advantage of the invention that in elastic force described in the terminal of the micro-fluidic chip its close position snap-in location
Folder, with the clamping limb of the elastic clip institute attaching install miniature ultrasonic transducer units, the low-power launched using it, high frequency
The ultrasonic wave of frequency range so that without inside strong hydrophobic micro-fluidic chip of surface chemical modification or surface chemical modification
Compatibility between its tube wall of pipeline and the test object aqueous solution is significantly increased, and this is existing by providing one for sample liquid stream
Real possibility；Meanwhile using its strong absorbability to ultrasonic wave of dimethyl silicone polymer substrate, in shorter distance
It is interior, it is, in from the terminal to the very short distance of only several centimeters yardsticks the sample introduction end, it is strong to reach ultrasonic wave
The rapid decrement of degree, the difference of the interfacial tension is thereby caused at the both ends of the micro-fluidic chip, and then, using this two
Pressure gap between its both ends for being formed of the difference of interfacial tension between end, driving sample liquid stream is in such a original
Flowed in this strong hydrophobic capillary channel to the terminal direction.By this case liquid stream drive scheme, entirely without must be to this
The substrate and its internal pipeline of dimethyl silicone polymer material carry out any surface chemical modification or chemical modification, altogether dispense with
The laborious procedures of the surface chemical modification or chemical modification；And setting for traditional Micropump etc is altogether dispensed with
It is standby；On the other hand, the ultrasonic wave of the low-power, high-frequency band, additionally it is possible to contain the large biological molecule in sample at this without modification
Naked its inner surface of pipeline of dimethyl silicone polymer substrate on absorption, and then contain its body of the dimethyl silicone polymer substrate
The effect of swallowing up of relatively described large biological molecule；The Reversible binding thing of the antigen, antibody and antigen and antibody is all certainly
Belong to the type of described large biological molecule；Because described suction-operated and the described effect of swallowing up effectively are contained,
Therefore, dependence test result will be better able to objectively reflect actual conditions；The effect of the low-power, high-frequency band ultrasonic wave,
Certainly also include facilitating the Reversible binding between antigen, antibody react it is quick reach, this causes dependence test operates can be with
Completed than faster speed.
Due to surface chemical modification or chemistry for its relevant surfaces of the dimethyl silicone polymer substrate need not be carried out
Modified operation, therefore, this surface chemical modification layer or chemically modified layer not need to exist, then, the poly dimethyl
Its body phase interior polymer molecule of siloxanes substrate constantly diffuses to the surface automatically, migrate caused by it to the surface chemistry
The damaging influence of decorative layer or chemically modified layer is also just not present.
It is related that the technical scheme of this case has dissolved its application to dimethyl silicone polymer substrate addressed above totally
A series of technical barriers.Based on this case scheme, the very cheap polydimethyl siloxane material of this kind is just possible to micro- at this
It is prepared by fluidic chip, production, using etc. field play bigger effect.
The miniature ultrasonic transducer units have been installed in fixation on the elastic clip its clamping limb in this case structure, and the structure carries
A function of facilitating the device to disassemble is supplied, in this way, the elastic clip just can together with miniature ultrasonic transducer units appended thereon
It is enough to be easily mutually disengaged with the micro-fluidic chip, then, the component that the part can freely depart from just can circulate benignly it is heavy
It is multiple to use many times；The architectural feature is advantageous to save the use cost of the device.
Brief description of the drawings
Fig. 1 is the schematic diagram of this case device embodiment chip part construction, it is shown that the vertical view of this structure
The structural form of chip internal pipeline and each electrode and each related liquid pool under angle, the elastic clip is not depicted in the figure
And the miniature ultrasonic transducer units and other annexes.
Fig. 2 is its rough outside side view of this case device.
In figure, 1,2,10 be the different liquid pool of three installation positions respectively, and 3 be manifold shape turnout, and 4,7,11,14 are respectively
Installation position is different but four laterals parallel with one another for forming UNICOM's structure in parallel, and 5 be its that be installed in lateral 4
Specific antibody material in the gold size sensitivity membrane structure of top layer is the working electrode of cholera TP0821 antibody, and 6 be to be installed in branch
The specific antibody material in its top layer gold size sensitivity membrane structure in pipeline 7 is the working electrode of cholera TP0319 antibody, 12
It is that specific antibody material in its top layer gold size sensitivity membrane structure being installed in lateral 11 is cholera TP0624 antibody
Working electrode, 13 be specific antibody material in its top layer gold size sensitivity membrane structure being installed in lateral 14 for suddenly
The working electrode of random O139 mycoproteins antibody, 8 be to electrode, and 9 be reference electrode, and 15 be elastic clip, and 16,21 be elastic force respectively
Two clamping limbs of folder, 17 be the terminal of the micro-fluidic chip, and 18 be the sample introduction end of the micro-fluidic chip, and 19 be poly-
The substrate of dimethyl siloxane material, 20 be cover plate, and 22 be miniature ultrasonic transducer units, and 23 be higher-order of oscillation electric signal transmission electricity
Cable, 24 be tension spring；The spring clamp structure in legend is only the legend structure of signal, and actual spring clamp structure is not limited to this
Legend spring clamp structure；Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive
It is dynamic, the flow direction of its sample liquid stream.
Embodiment
In this case that Fig. 1 and Fig. 2 are shown embodiment, the structure of the device includes multichannel micro-fluidic chip, should
The structure of micro-fluidic chip includes being bonded to each other the substrate 19 and cover plate 20 of installing together, and the substrate 19 and cover plate 20 are
What is formed via mould pressing process or etching technics contained in plate object or tablet, that face towards the cover plate 20 of the substrate 19
Channel structure, the substrate 19 also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics
Or the window structure that simple drilling technology is formed, it is bonded to each other the substrate 19 being installed together and is built into jointly with the cover plate 20
Micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the liquid pool are liquid pool 1, liquid pool 2, liquid pool
10, the locations of structures of the pipeline is located at the interface zone that the substrate 19 is bonded to each other with the cover plate 20, and its side of the window is by this
Cover plate 20 blocks and opposite side opens, and the locations of structures of the window is exactly the liquid pool 1, liquid pool 2, the locations of structures of liquid pool 10,
The quantity of the liquid pool is three, and two liquid pools therein are that liquid pool 1 and liquid pool 2 its locations of structures are located at the micro-fluidic chip
Sample introduction end 18, a remaining liquid pool are its chip when liquid pool 10 its locations of structures is located at the micro-fluidic chip actual sample introduction test
The terminal 17 of interior liquid flowing, the terminal 17 are located remotely from each other with the sample introduction end 18, and one end of the pipeline is via being similarly positioned in the phase
The manifold shape turnout 3 for the interface zone being mutually bonded respectively with the liquid pool 1 positioned at sample introduction end 18 and the UNICOM of liquid pool 2, the pipeline
The other end and the remaining liquid pool of the terminal 17 positioned at the micro-fluidic chip be the UNICOM of liquid pool 10, and, according to
Sequence is respectively installed in working electrode in the pipeline on diverse location and to electrode 8 and reference electrode 9, the working electrode
It is made up of conductive electrode and the gold size sensitive membrane for having embedded cholera specific antibody being attached on the conductive electrode, should
The construction of pipeline is in parallel construction, and the pipeline in parallel construction is made up of four lateral parallel connections, the working electrode
Quantity be four, the installation positions of four working electrodes is respectively in four laterals, this four work electricity
Pole is working electrode 5, working electrode 6, working electrode 12, working electrode 13 respectively, and, four its top layer of working electrode gold
Specific antibody in glue sensitivity membrane structure is the four kinds of cholera antibody materials that can be specifically bound to cholera antigen respectively, and this four
Kind antibody materials are cholera TP0821 antibody and cholera TP0319 antibody and cholera TP0624 antibody and cholera respectively
O139 mycoprotein antibody, for specifically deploying, 5 be in its top layer gold size sensitivity membrane structure being installed in lateral 4
Specific antibody material be cholera TP0821 antibody working electrode, 6 be that its top layer gold size being installed in lateral 7 is quick
Feel the working electrode that the specific antibody material in membrane structure is cholera TP0319 antibody, 12 are installed in lateral 11
Specific antibody material in its top layer gold size sensitivity membrane structure is the working electrode of cholera TP0624 antibody, and 13 be to be installed in point
The specific antibody material in its top layer gold size sensitivity membrane structure in branch pipe(tube) 14 is the work of cholera O139 mycoprotein antibody
Make electrode, the working electrode 5, working electrode 6, working electrode 12, working electrode 13 its material are gold material or thermal decomposition
Conducting polymer material, the working electrode 5, working electrode 6, working electrode 12, working electrode 13 its pattern present sheet or
Thread, emphasis is, its material of the substrate 19 is dimethyl silicone polymer material, and its surface of substrate 19 is the table of primary form
Face, the surface of the primary form its be intended to refer to not by any surface chemical modification or any surface chemical modification should
The surface of the primary form of material, the structure of the device also include elastic clip 15, two opposite clamping limbs of the elastic clip 15
16th, 21 snap-in locations are in the position of the neighbouring terminal 17 of the micro-fluidic chip, a clamping limb at least in
Upper attaching, which is fixed, is equiped with miniature ultrasonic transducer units 22, and in legend, the miniature ultrasonic transducer units 22 are to attach fixed installing
On one of which clamping limb 21, and, higher-order of oscillation electric signal transmission cable 23, the higher-order of oscillation electric signal transmission cable
23 one end links together with the miniature ultrasonic transducer units 22；The elastic clip 15 provides one and facilitates what the device was disassembled
Function；Its major function of the miniature ultrasonic transducer units 22 is in the actual sample introduction test of micro-fluidic chip, is launched using it
Ultrasonic wave reduce the interfacial tension between sample solution and the inwall of the pipeline, can be compatible, also, utilize institute
State sample introduction end 18 and the distance between the terminal 17 and the installation position of miniature ultrasonic transducer units 22 difference and its institute
The difference on ultrasonic intensity experienced, its interfacial tension of sample introduction end 18 described in induced synthesis and described its interface of terminal 17
Difference between power, the micro-fluidic chip both ends are that the interfacial tension difference between sample introduction end 18 and terminal 17 can be in the miniflow
The both ends for controlling chip are to form pressure gap between sample introduction end 18 and terminal 17, and the pressure gap can drive sample solution to institute
State the flowing of the direction of terminal 17；Its function of miniature ultrasonic transducer units 22 also ultrasonic wave including being launched with it is checked in sample
Its absorption on the inner surface of pipeline of contained large biological molecule, and then check the base of the dimethyl silicone polymer material
Swallow up effect of its body phase of piece 19 to the large biological molecule；The substrate 19 of the dimethyl silicone polymer material its function include with
Cover plate 20 and working electrode 5, working electrode 6, working electrode 12, working electrode 13 and electrode 8 and reference electrode 9 are together built
The micro-fluidic chip, it is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and also include with it to ultrasonic wave
The property absorbed strongly, ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic chip terminal between the sample introduction end
Limited short distance within realize the rapid decrement of ultrasonic intensity, its locations of structures is located at the actual sample introduction of the micro-fluidic chip
A remaining liquid pool for the terminal that liquid flows is also referred to as terminal liquid pool in its chip during test, is filled in the terminal liquid pool
There are some high hydroscopic resin particles, its opening end of the terminal liquid pool is covered by breathable microporous film.
Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, its try
The flow direction of sample liquid stream.
Miniature ultrasonic transducer units 22 and high frequency vibrating that the elastic clip 15 is depicted without in Fig. 1 and is set up thereon
Swing electric signal transmission cable 23；Also, the higher-order of oscillation electric signal generator and multiple tracks electricity are depicted without in Fig. 1 and Fig. 2
The associate members such as chem workstation.
Involved elastic clip 15 is commercially available.It is available for the commercially available alternative spring clamp structure and make that this case structure uses
Type and size etc., quality is various, and specific elastic clip pattern can be selected as needed.
Involved miniature ultrasonic transducer units 22 are commercially available；It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal transmission cable 23 is commercially available；Can also be special to ultrasonic transducer producer or cable
Industry producer customizes.
Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；It can also determine to relevant manufacturers
System.
Each working electrode in this example structure and can be respectively via each special electricity to electrode and reference electrode
Cable or say is being got lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as annex or saying interface connection of getting lines crossed.
Claims (10)
1. being carried out the easily-disassembled cholera diagnosis device of liquid stream driving by means of interfacial characteristics, the structure of the device includes leading to more
Road micro-fluidic chip, the structure of the micro-fluidic chip include being bonded to each other the substrate and cover plate of installing together, the substrate and
Cover plate is plate object or tablet, and that face towards the cover plate of the substrate is contained via mould pressing process or etching technics shape
Into channel structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etch work
The window structure that skill or simple drilling technology are formed, it is bonded to each other the substrate being installed together and is built into jointly with the cover plate
Micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the locations of structures of the pipeline are located at the substrate with being somebody's turn to do
The interface zone that cover plate is bonded to each other, its side of the window is blocked by the cover plate and opposite side opens, the locations of structures of the window
It is exactly the locations of structures of the liquid pool, the quantity of the liquid pool is three, and it is micro- that its locations of structures of two liquid pools therein is located at this
The sample introduction end of fluidic chip, its locations of structures of a remaining liquid pool are located at its chip when the actual sample introduction of the micro-fluidic chip is tested
The terminal of interior liquid flowing, the terminal are located remotely from each other with the sample introduction end, and one end of the pipeline is bonded to each other via this is similarly positioned in
Interface zone manifold shape turnout respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline with positioned at should
A remaining liquid pool UNICOM for the terminal of micro-fluidic chip, and, sequentially it is respectively installed in different positions in the pipeline
The working electrode put and to electrode and reference electrode, the working electrode is by conductive electrode and is attached to the conduction
Property electrode on embedded cholera specific antibody gold size sensitive membrane form, the construction of the pipeline is in parallel construction, described to be in
The pipeline of parallel construction is made up of four lateral parallel connections, and the quantity of the working electrode is four, four working electrodes
Installation position respectively in four laterals, and, its top layer gold size sensitivity membrane structure of four working electrodes
In specific antibody be the four kinds of cholera antibody materials that can be specifically bound to cholera antigen respectively, four kinds of antibody materials point
It is not that cholera TP0821 antibody and cholera TP0319 antibody and cholera TP0624 antibody and cholera O139 mycoproteins resist
Body, its material of the working electrode are gold material or thermal decomposition conducting polymer material, and its pattern of the working electrode is presented
Sheet is thread, it is characterised in that its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is primary form
Surface, the surface of the primary form its be intended to refer to and do not pass through any surface chemical modification or any surface chemical modification
The material primary form surface, the structure of the device also includes elastic clip, two opposite clamping limbs of the elastic clip
Snap-in location attaches solid on the position of the neighbouring terminal of the micro-fluidic chip a, clamping limb at least in
Surely miniature ultrasonic transducer units are equiped with, and, higher-order of oscillation electric signal transmission cable, the higher-order of oscillation electric signal transmission cable
One end linked together with the miniature ultrasonic transducer units；The elastic clip provides a function of facilitating the device to disassemble；
Its major function of the miniature ultrasonic transducer units is the ultrasonic wave launched using it in the test of micro-fluidic chip actual sample introduction
, can be compatible to reduce the interfacial tension between sample solution and the inwall of the pipeline, also, utilize the sample introduction end
And the distance between the terminal and the miniature ultrasonic transducer units installation position difference and its ultrasonic wave experienced
Difference between difference in intensity, its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension, this is micro-
Interfacial tension difference between the fluidic chip both ends can form pressure gap between the both ends of the micro-fluidic chip, the pressure
Power difference can drive sample solution to the end flow；Its function of the miniature ultrasonic transducer units also includes what is launched with it
Ultrasonic wave checks in sample contained its absorption on the inner surface of pipeline of large biological molecule, and then checks the poly- diformazan
Swallow up effect of its body phase of the substrate of radical siloxane material to the large biological molecule；The substrate of the dimethyl silicone polymer material
Its function includes with cover plate and working electrode and electrode and reference electrode is together built the micro-fluidic chip, and softness simultaneously has elasticity
The substrate of the dimethyl silicone polymer material its function also include with its property to the strong absorption of ultrasonic wave, ultrasonic wave is entered
Row is strong to be absorbed, and ultrasound is thereby realized within micro-fluidic chip terminal to the limited short distance between the sample introduction end
The rapid decrement of intensity of wave, its locations of structures are located at the end of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested
A remaining liquid pool at end is also referred to as terminal liquid pool, and some high hydroscopic resin particles, the end are filled with the terminal liquid pool
Liquid pool its opening end in end is covered by breathable microporous film.
2. the easily-disassembled cholera diagnosis device according to claim 1 that liquid stream driving is carried out by means of interfacial characteristics,
Characterized in that, the pipeline and the lateral and the manifold shape turnout are capillary channel.
3. the easily-disassembled cholera diagnosis device according to claim 1 that liquid stream driving is carried out by means of interfacial characteristics,
Characterized in that, the thermal decomposition conducting polymer is the conduction formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated
Property material.
4. the easily-disassembled cholera diagnosis device according to claim 1 that liquid stream driving is carried out by means of interfacial characteristics,
Characterized in that, the width or diameter of the working electrode be between 0.1 micron to 2000 microns, and, the work electricity
The length of pole is between 1 micron to 15000 microns.
5. the easily-disassembled cholera diagnosis device according to claim 1 that liquid stream driving is carried out by means of interfacial characteristics,
Characterized in that, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. the easily-disassembled cholera diagnosis device according to claim 1 that liquid stream driving is carried out by means of interfacial characteristics,
Characterized in that, the cover plate its material in structure is dimethyl silicone polymer material.
7. the easily-disassembled cholera diagnosis device according to claim 1 that liquid stream driving is carried out by means of interfacial characteristics,
Characterized in that, positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal
Air line distance between a remaining liquid pool is between 3 centimetres and 7 centimetres.
8. the easily-disassembled cholera diagnosis device according to claim 1 that liquid stream driving is carried out by means of interfacial characteristics,
Characterized in that, described its thickness of cover plate and substrate in structure is between 1.0 millimeters and 5.0 millimeters.
9. the easily-disassembled cholera diagnosis device according to claim 1 that liquid stream driving is carried out by means of interfacial characteristics,
Characterized in that, the structure of the device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission cable
Its other end is connected with the higher-order of oscillation electric signal generator.
10. the easily-disassembled cholera diagnosis device according to claim 1 that liquid stream driving is carried out by means of interfacial characteristics,
Characterized in that, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units, between 5 milliwatts and 5000 milliwatts, this is micro-
The frequency of its ultrasonic wave operationally launched of type ultrasonic transducer is between 100KHz and 12MHz.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610626997.0A CN107649202A (en) | 2016-07-26 | 2016-07-26 | The easily-disassembled cholera diagnosis device of liquid stream driving is carried out by means of interfacial characteristics |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610626997.0A CN107649202A (en) | 2016-07-26 | 2016-07-26 | The easily-disassembled cholera diagnosis device of liquid stream driving is carried out by means of interfacial characteristics |
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| CN107649202A true CN107649202A (en) | 2018-02-02 |
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Citations (3)
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| CN101620227A (en) * | 2009-07-12 | 2010-01-06 | 宁波大学 | Multi-channel chip for cholera diagnosis based on structural conductive macromolecular material technology |
| CN101817495A (en) * | 2010-03-25 | 2010-09-01 | 湖南大学 | Micro fluid control chip and preparation method and application thereof |
| 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 |
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2016
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|---|---|---|---|---|
| CN101620227A (en) * | 2009-07-12 | 2010-01-06 | 宁波大学 | Multi-channel chip for cholera diagnosis based on structural conductive macromolecular material technology |
| CN101817495A (en) * | 2010-03-25 | 2010-09-01 | 湖南大学 | Micro fluid control chip and preparation method and application thereof |
| 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 |
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Application publication date: 20180202 |