CN107649205A - The cholera diagnosis micro fluidic device that can be fast removed for the annex for driving liquid stream - Google Patents
The cholera diagnosis micro fluidic device that can be fast removed for the annex for driving liquid stream Download PDFInfo
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- CN107649205A CN107649205A CN201610627098.2A CN201610627098A CN107649205A CN 107649205 A CN107649205 A CN 107649205A CN 201610627098 A CN201610627098 A CN 201610627098A CN 107649205 A CN107649205 A CN 107649205A
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
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- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
- B01L2400/0439—Moving fluids with specific forces or mechanical means specific forces vibrational forces ultrasonic vibrations, vibrating piezo elements
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Abstract
The present invention relates to a kind of cholera diagnosis micro fluidic device for driving the annex of liquid stream fast to remove, belong to analysis testing field.Serial problem be present if for making the substrate of cholera diagnosis micro-fluidic chip in dimethyl silicone polymer i.e. PDMS that is cheap and easily processing；Its surface of the PDMS material is strongly hydrophobic, and targetedly surface is modified or surface modification, its effect are difficult to persistently, and this case aims to solve the problem that the serial relevant issues.This case main points are, the selected PDMS with ecosystem surface of substrate, and 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 cholera diagnosis micro fluidic device for driving the annex of liquid stream fast to remove, belong to
Analyze testing field.
Background technology
The micro-fluidic cholera diagnostic techniques background of associated multi-channel, may refer to the patents of invention such as CN 200910150930.4
Application case.
Only for the microflow control technique overall general picture of itself, famous micro-fluidic expert Mr. Lin Ping Cheng may refer to not
The monograph " diagram Microfluid based Lab on a chip " gone out before long, the monograph is published via Science Press, and the monograph is to micro-fluidic
Past of technology, now, and, vision of the future etc. etc., suffer from detail, be deep into long discussion of detail.
So, the Important Problems of this case that to have a talk below concern.
The basic framework of micro-fluidic chip, including be etched with the substrate of small fluid course and fit together therewith
Cover plate, the small fluid course on the substrate, before upper cover plate is assembled, it is apparent on see to be exactly some micro-channels, to wait until
After covering cover plate thereon, just really closure forms the small fluid course, the conduit inner surface of the micro-channel together with
The part cover plate that surround the micro-channel forms described small fluid course together；So, it is clear that after assembling completes
The small fluid course, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, should
The state or property of micro-channel inner surface substantially determine the integrality or property of the small fluid course；Therefore say, this
The inner surface state or inner surface property of micro-channel of the individual structure on substrate are key factors；In principle, it is any can
The material of its solid forms is kept or kept substantially, can be used to make substrate and cover plate, such as, it can act as substrate and lid
The material of piece can be monocrystalline silicon piece, quartz plate, sheet glass, high polymer for example dimethyl silicone polymer, polymethyl methacrylate,
Makrolon etc.；Certainly, the selection of substrate and the selection of cover plate be able to can also be differed with identical；From material consumption, make
From the point of view of difficulty and application popularization prospect etc. etc., not small difference, the especially choosing of that substrate between these materials be present
Material, have a great influence.
In various substrate making materials, dimethyl silicone polymer, i.e. PDMS, comparatively very easily shaping, at this
It is extremely simple that micro-channel is made on the substrate of sample, and the lower cost for material, base is made with the polydimethyl siloxane material
Piece, micro-channel, and the cover plate phase made with the cheap material such as glass or polypropylene or other plastic sheets are being suppressed or etched thereon
Coordinate, be a kind of more satisfactory selection seemingly；Certainly, patch material can also select to use cheap dimethyl silicone polymer
Material：So, this substrate selection is the scheme of polydimethyl siloxane material, and material is extremely cheap, and making is extremely simple, seems
It should be extremely easy to popularize, promote.
But thing is really not so simple.
First, this polydimethyl siloxane material, that is, the material that alphabetical PDMS is referred to of abridging, itself are a kind of strong
Strong hydrophobic material, micro-channel is built on this material, if without being operated for the modified of the micro-channel surface, that
, after overall assembling is completed, that is, after covering cover plate, because the micro-channel its inner surface in structure occupies most liquid
The inner surface of circulation road, then, its strong hydrophobic property of the PDMS micro-channels inner surface, is deciding factor, it can cause
Similar to the aqueous solution the fine liquid stream of polar liquid by becoming very difficult, its flow resistance is big, or even in general is micro-
Pump is all difficult to promote, certainly, if cover plate also selects to use the PDMS material, then, problem is substantially identical, similar；
Therefore, among prior art, modification is modified particular for the micro-channel inner surface on the PDMS material, is necessary behaviour
Make；So, this is pretty troublesome for the modified operation of PDMS micro-channel inner surfacesThat falls nor this problem, is formed tight
Weight technology puzzlement, be another problem：PDMS polymer molecules inside its body phase of this PDMS material substrate have automatic
The characteristic diffuse to the surface, migrated, the spy that this substrate body phase inside PDMS polymer molecules are diffused to the surface, migrated automatically
Property, the state after modification by its inner surface of that micro-channel of surface modifying and decorating will be caused can not to maintain long enough
Time, the holding time for micro-channel its inner surface state after that is surface-modified be substantially only sufficient to complete laboratory internal
The time of test experiments needs；In other words, by surface modification or the PDMS micro-channel inner surfaces of surface modification, it is modified
The surface state that is formed can not be lasting afterwards or after saying modification, but soon automatically tends to or say and become surface modification again
Surface state before, the strong hydrophobic surface state of that script is returned in the shorter time, then, just think, this
The micro-fluidic chip of sample can largely make, mass storage, be widely popularized, and answer is it is obvious that is, impossible.This
Micro-channel on PDMS material, if not doing surface modification, similar to the aqueous solution the fine liquid stream of polar solvent can not pump it is logical
Cross, chip also cannot just use；And if having done surface modification, its state after modifying can not be persistently kept again, or together
Sample can not popularization and application.
So, how to accomplish that substrate can either be made using cheap PDMS material, and the microflute can be released
Road inner surface decorating state can not persistently, chip can not largely make, largely lay in and then be widely popularized and such a make ability
The puzzlement that the numerous professionals in domain are entangled with for a long time, the highly difficult problem that exactly one its obvious technology barrier can not despise.
Be present many year in the highly difficult problem, so far, not yet properly settled.
Second, the PDMS material of non-surface modification, it is stated that, its surface is strongly hydrophobic above, this strong hydrophobic
Material surface and also have another problem, that is, this strong hydrophobic PDMS surfaces can adsorb large biological molecule, and
And these adsorbed large biological molecules can also further depression further on PDMS surfaces, gradually fall into it is gradually deep, until
It is heavy to be trapped within the body phase of PDMS substrates, in fact, this process, partly it is also due to PDMS material body phase interior polymer
Molecule, which has, to be diffused to the surface, caused by travel motion；Such case, it can also be explained from another angle, i.e. continue not
Disconnectedly from inside PDMS body phases to those polymer molecules of its diffusion into the surface, migration, its result moved, be little by little by that
It has been involved in a bit by the large biological molecule of adsorption within the body phase of PDMS substrates, briefly, these adsorbed biologies
Macromolecular is exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up the phenomenon of large biological molecule, its institute
Caused by influence, necessarily cause the severe deviations of all kinds of test data of experiment for being related to large biological molecule.
As described above, the problem of PDMS substrates, is, its not only adsorption large biological molecule, and swallow up biological big point
Son, so, as the large biological molecule of experiment test object, its disappearance will not stop because surface saturation is adsorbed, and
It is, it is constantly adsorbed, also constantly swallowed up.
On PDMS substrates, its body phase is constantly swallowed up and tests showing for associated biomolecule macromolecular in related experiment test process
As, it is to say that another kind, which is explained, substantial amounts of Minute pores in PDMS body phases be present, associated biomolecule macromolecular by after adsorption,
Depression enters these Minute pores, and then is swallowed up；However, inventor thinks, those can allow the sky of miniature scale
Qi leel squeezes into the Minute pores therebetween, not equal to saying that they also can directly allow the large biological molecule of relative large scale to enter
Enter, both difference on yardstick are huge, must not make sweeping generalizations.Explanation is bypassed, in any case, as dependence test analysis object
Large biological molecule is adsorbed by PDMS substrate micro-channels inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is person in charge of reception at ceremonies
Phenomenon existing for sight.
, can be from containment PDMS surfaces pair in order to prevent swallow up effect of this PDMS substrate bodies relative to large biological molecule
The absorption of large biological molecule addresses, and method is chemically modified modification aiming at the PDMS material surface, for
For PDMS is the situation of substrate material, modification exactly is chemically modified to the surface of described micro-channel part, by changing
The micro-channel inner surface of modification is learned, its absorption to large biological molecule can be contained, and then avoid large biological molecule
Swallowed up by PDMS substrate body phases；But or that old problem, that is, the chemical modification on PDMS material surface is modified
Surface state afterwards can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface, move automatically
The process of shifting, it soon can become that micro-channel inner surface state being modified by surface chemical modification again script strong and dredge
Water and the state of strong adsorption large biological molecule, in other words, no matter how professionals in the field turn from side to side, the PDMS bases
Its micro-channel inner surface of piece is always rapidly to strong hydrophobic surface state evolution.
So, how can either obtain that PDMS material price is extremely cheap, substrate makes extremely easy benefit, and can is enough
Reach and contain the absorption process of the PDMS substrate micro-channel inner surfaces to large biological molecule for a long time, and then prevent PDMS substrate body phases
The effect of swallowing up to large biological molecule so that related chip manufactured goods be able to maintain that one it is prolonged enough, reasonably guarantee the quality
Phase, it is exactly a very intractable problem.The problem equally makes this area numerous as another problem addressed above
Professional is entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise.
Also be present many year in the problem, so far, also not yet properly settled.
The content of the invention
The technical problem to be solved by the invention is to provide a package solution, solves totally above
Two problems addressed, also, the solution is applied to cholera diagnosis multichannel micro-fluidic chip field, formed a kind of
Multichannel micro-fluidic device is used in new cholera diagnosis.
The present invention solves the technical problem by following scheme, and the device that the program provides is a kind of for driving liquid stream
The cholera diagnosis micro fluidic device that can fast remove of annex, the structure of the micro fluidic device includes multichannel micro-fluidic core
Piece, the structure of the micro-fluidic chip include being bonded to each other the substrate and cover plate of installing together, and the substrate and cover plate are plate
The conduit knot via mould pressing process or etching technics formation is contained in shape thing or tablet, that face towards the cover plate of the substrate
Structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or simply beat
The window structure that hole technique is formed, it is bonded to each other the substrate being installed together and has been built into jointly with the cover plate and contain pipeline knot
The micro-fluidic chip of structure and the liquid pool structure being attached thereto, the locations of structures of the pipeline are located at the substrate and mutually pasted with the cover plate
The interface zone of conjunction, 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 liquid
The locations of structures in pond, the quantity of the liquid pool is three, and its locations of structures of two liquid pools therein is located at the micro-fluidic chip
Sample introduction end, its locations of structures of a remaining liquid pool are located at liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested
Terminal, the terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is via being similarly positioned in the interface zone being bonded to each other
Manifold shape turnout respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline and be located at the micro-fluidic chip
The terminal a remaining liquid pool UNICOM, and, be sequentially respectively installed in the work on diverse location in the pipeline
Electrode and to electrode and reference electrode, the working electrode is by conductive electrode and is attached on the conductive electrode
The gold size sensitive membrane for having embedded cholera specific antigen is formed, and the construction of the pipeline is in parallel construction, and described is in parallel construction
Pipeline is made up of four lateral parallel connections, and the quantity of the working electrode is four, the installation position of four working electrodes
Respectively in four laterals, and, the specificity in its top layer gold size sensitivity membrane structure of four working electrodes
Antigen is the four kinds of cholera antigenic substances that can be specifically bound to cholera antibody respectively, and four kinds of antigenic substances are cholera respectively
TP0821 antigens and cholera TP0319 antigens and cholera TP0624 antigens and cholera O139 antigens, the working electrode its
Material is that sheet or thread is presented in gold material or thermal decomposition conducting polymer material, the working electrode its pattern, and emphasis is,
Its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, the table of the primary form
Face its be intended to refer to the not no primary form of the material by any surface chemical modification or any surface chemical modification
Surface, the structure of the micro fluidic device also include elastic clip, and two opposite clamping limb snap-in locations of the elastic clip are micro- at this
The position of the neighbouring terminal of fluidic chip, attach on a clamping limb at least in it is fixed be equiped with it is miniature super
Acoustic wave transducer, and, higher-order of oscillation electric signal transmission cable, one end of the higher-order of oscillation electric signal transmission cable is miniature with this
Ultrasonic transducer links together；The elastic clip provides a function of facilitating the micro fluidic device to disassemble；This is miniature super
Its major function of acoustic wave transducer is that the ultrasonic wave launched using it is tried to reduce in the actual sample introduction test of micro-fluidic chip
Interfacial tension between the inwall of sample solution and the pipeline, can be compatible, also, utilizes the sample introduction end and described
In the distance between terminal and the miniature ultrasonic transducer units installation position difference and its ultrasonic intensity experienced
Difference between difference, its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension, the micro-fluidic chip
Interfacial tension difference between the both ends can form pressure gap between the both ends of the micro-fluidic chip, the pressure gap meeting
Sample solution is driven to the end flow；The ultrasonic wave that its function of the miniature ultrasonic transducer units also includes being launched with it is held back
Only contained its absorption on the inner surface of pipeline of large biological molecule in sample, and then check the dimethyl silicone polymer
Swallow up effect of its body phase of the substrate of material to the large biological molecule；Its function bag of the substrate of the dimethyl silicone polymer material
Include with cover plate and working electrode and the micro-fluidic chip together built to electrode and reference electrode, it is soft and have elasticity this poly- two
Its function of the substrate of methylsiloxane material also includes with its property to the strong absorption of ultrasonic wave, and ultrasonic wave is inhaled strongly
Receive, and thereby realize ultrasonic intensity within micro-fluidic chip terminal to the limited short distance between the sample introduction end
Rapid decrement, its locations of structures are located at the described of the terminal that liquid flows in its chip when the actual sample introduction of the micro-fluidic chip is tested
A remaining liquid pool is also referred to as terminal liquid pool, is filled with some high hydroscopic resin particles in the terminal liquid pool, the terminal liquid pool its
Opening end is covered by breathable microporous film.
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 antigen solution uniformly, is used a little
Sample instrument point sample is coated on specified structure position, and forms its drying and forming-film.Cholera specificity in the gold size sensitive membrane
Antigen is the cholera antigen of horseradish peroxidase or glucose oxidase mark, and the gold size sensitive membrane has been included as solid
Determine above-mentioned each cholera specific antigen and introduce complementary medium therein, the complementary medium such as chitosan, acetic acid are fine
Dimension is plain, gelatin is therein a kind of or their mixture.
The pipeline and the lateral and the manifold shape turnout in the microfluidic chip structure, in it
Footpath size may each be arbitrarily selected size, still, for as far as possible less with prepare liquid sample and reduction reagent loss etc.
Consideration, the pipeline and the lateral and the manifold shape turnout preferably select capillary level passage, institute
The passage for stating capillary level implies that its internal diameter passage suitable with the internal diameter of the capillary on ordinary meaning.The capillary is in it
The shape of cross section of portion's passage can be arbitrary shape, and the shape of cross section is for example circular, oval, square, rectangle, bar
Shape, naturally it is also possible to it is the linear of bending arbitrarily be present, also, the interior shape of the capillary is with the extension of pipeline,
The shape of cross section of different parts can also allow to be different shapes.Only for the word of capillary one, its art-recognized meanings is public
Know.
What is be related in structure is the electrode of microsize to electrode and reference electrode, and its electrode shape, which may each be, appoints
The selected shape of meaning, the arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..It is described
Art-recognized meanings to electrode and the reference electrode vocabulary of itself are known.
It is related to several liquid pools in this case microfluidic chip structure, the liquid pool is the pond shape or capsule for transitional liquid storage
Shape constructs, and its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, and the cavity shape is for example round
Cylindrical cavity shape, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..The size of the liquid pool can be any
Selected size, still, in order to as far as possible less with prepare liquid sample and reduce reagent loss, the liquid pool be preferably capable of with
The liquid pool of the microminiature of capillary matching.
Only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field,
It is known.
Various sizes, variously-shaped ultrasonic transducer are commercially available；Its size of commercially available miniature ultrasonic transducer units
It may diminish to the magnitude only calculated with millimeter.
Only with regard to miniature ultrasonic transducer units its technique for fixing on general industry application solid body surface its
It is known general technology for the professional in ultrasonic technology field for body.This case is not to this expansion superfluous words.
Only with regard to naked PDMS substrates itself micro-channel molding or lithographic technique for, be open-and-shut known skill
Art；Similarly, the technology of hole-opening is even more known simple technique on naked PDMS substrates.This case is not also superfluous to this expansion
Speech.
The industrial products market of involved its all size of higher-order of oscillation electric signal transmission cable is on sale.
The structure of the micro fluidic device can also include higher-order of oscillation electric signal generator；The higher-order of oscillation electric signal passes
Its other end of transmission cable can be connected with the higher-order of oscillation electric signal generator.
The involved higher-order of oscillation electric signal generator technology of itself, come for the professional in ultrasonic technology field
Say, be simple and known；The higher-order of oscillation electric signal generator can customize to ultrasonic instrument specialized factory.
The preferred scope of its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 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 antibody are detected.
Corresponding four kinds of cholera antibody is detected with four kinds of cholera antigens, with detecting corresponding four with four kinds of cholera antibody
Kind cholera antigen, similarly, can cholera diagnosis；The principle of its foundation is, necessarily antigen, antibody in cholera patient
And deposit, and mutual Reversible binding forms reversible conjugate, therefore, antibody and thereby cholera diagnosis is detected with antigen, with
Antibody goes to detect antigen and cholera diagnosis, can reach diagnostic purpose.Certainly, its corresponding electrode sensitive of different means is repaiied
Adorn layer technically and differ.
The specific detection of this case micro-fluidic chip is as follows using step：
1st, blood serum sample liquid is added in micro-pipe road, under ultrasonic wave driving, various cholera antibody molecules are by each logical
The cholera specific antigen for the corresponding horseradish peroxidase-labeled that gold size sensitive membrane embeds captures on electrode surface in road.
2nd, the cholera specific antigen of horseradish peroxidase-labeled is formed immune multiple with the cholera antibody in blood serum sample
Compound.
3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, it is above-mentioned using amperometric detection
Curent change caused by reaction, it is derived from the species and content of various analytes.
4th, result is subjected to comprehensive analysis, comprehensive diagnos is carried out to cholera antibody.
It is an advantage of the invention that 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 micro fluidic device embodiment chip part construction, it is shown that this structure
Depression angle under chip internal pipeline and the structural form of each electrode and each related liquid pool, do not depict in the figure described
Elastic clip and the miniature ultrasonic transducer units set up thereon and other annexes.
Fig. 2 is its rough outside side view of this case micro fluidic device.
In figure, 1,2,10 be the different liquid pool of three installation positions respectively, and 3 be manifold shape turnout, and 4,7,11,14 are respectively
Installation position is different but four laterals parallel with one another for forming UNICOM's structure in parallel, and 5 be its that be installed in lateral 4
Specific antigenic substance in the gold size sensitivity membrane structure of top layer is the working electrode of cholera TP0821 antigens, and 6 be to be installed in branch
The specific antigenic substance in its top layer gold size sensitivity membrane structure in pipeline 7 is the working electrode of cholera TP0319 antigens, 12
It is that specific antigenic substance in its top layer gold size sensitivity membrane structure being installed in lateral 11 is cholera TP0624 antigens
Working electrode, 13 be specific antigenic substance in its top layer gold size sensitivity membrane structure being installed in lateral 14 for suddenly
The working electrode of random O139 antigens, 8 be to electrode, and 9 be reference electrode, and 15 be elastic clip, and 16,21 be two of elastic clip respectively
Clamping limb, 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 dimethyl silicon
The substrate of oxygen alkane material, 20 be cover plate, and 22 be miniature ultrasonic transducer units, and 23 be higher-order of oscillation electric signal transmission cable, and 24 are
Tension spring；The spring clamp structure in legend is only the legend structure of signal, and actual spring clamp structure is not limited to the legend bullet
Power clamping structure；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.
Embodiment
In this case that Fig. 1 and Fig. 2 are shown embodiment, the structure of the micro fluidic device includes multichannel micro-fluidic core
Piece, the structure of the micro-fluidic chip include being bonded to each other the substrate 19 and cover plate 20 of installing together, the substrate 19 and cover plate
20 be plate object or tablet, and that face towards the cover plate 20 of the substrate 19 is contained via mould pressing process or etching technics
The channel structure of formation, the substrate 19 also containing be connected with the channel structure and pierce the substrate via mould pressing process, quarter
The window structure that etching technique or simple drilling technology are formed, is bonded to each other the substrate 19 being installed together and the cover plate 20 is common
Be built into the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the liquid pool be liquid pool 1, liquid pool 2,
Liquid pool 10, the locations of structures of the pipeline are located at the interface zone that the substrate 19 is bonded to each other with the cover plate 20, its side of the window
Blocked and opposite side opening by the cover plate 20, the locations of structures of the window is exactly the liquid pool 1, liquid pool 2, the structure bit of liquid pool 10
Put, the quantity of the liquid pool is three, and two liquid pools therein are that liquid pool 1 and liquid pool 2 its locations of structures are located at the micro-fluidic core
The sample introduction end 18 of piece, a remaining liquid pool be when liquid pool 10 its locations of structures is located at the micro-fluidic chip actual sample introduction test its
The terminal 17 that liquid flows in chip, the terminal 17 is located remotely from each other with the sample introduction end 20, and one end of the pipeline is via being similarly positioned in
The manifold shape turnout 3 of the interface zone being bonded to each other, should respectively with the liquid pool 1 positioned at sample introduction end 18 and the UNICOM of liquid pool 2
The other end of pipeline and a remaining liquid pool for the terminal 17 positioned at the micro-fluidic chip are the UNICOM of liquid pool 10, with
And sequentially it is respectively installed in working electrode in the pipeline on diverse location and to electrode 8 and reference electrode 9, the work
Make electrode by conductive electrode and the gold size sensitive membrane for having embedded cholera specific antigen being attached on the conductive electrode
Form, the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of four lateral parallel connections, the work
The quantity for making electrode is four, and the installation position of four working electrodes is located in four laterals respectively, this four
Working electrode is working electrode 5, working electrode 6, working electrode 12, working electrode 13 respectively, and, four working electrodes its
Specific antigen in the gold size sensitivity membrane structure of top layer is the four kinds of cholera antigen things that can be specifically bound to cholera antibody respectively
Matter, four kinds of antigenic substances be respectively cholera TP0821 antigens and cholera TP0319 antigens and cholera TP0624 antigens and
Cholera O139 antigens, for specifically deploying, 5 be the spy in its top layer gold size sensitivity membrane structure being installed in lateral 4
Specific Antigen material is the working electrode of cholera TP0821 antigens, and 6 be its top layer gold size sensitive membrane being installed in lateral 7
Specific antigenic substance in structure is the working electrode of cholera TP0319 antigens, and 12 be its table being installed in lateral 11
Specific antigenic substance in layer gold size sensitivity membrane structure is the working electrode of cholera TP0624 antigens, and 13 be to be installed in branched pipe
The specific antigenic substance in its top layer gold size sensitivity membrane structure in road 14 is the working electrode of cholera O139 antigens, the work
It is gold material or thermal decomposition conducting polymer material to make electrode 5, working electrode 6, working electrode 12, working electrode 13 its material
Sheet or thread is presented in matter, the working electrode 5, working electrode 6, working electrode 12, working electrode 13 its pattern, and emphasis is,
Its material of the substrate 19 is dimethyl silicone polymer material, and its surface of substrate 19 is the surface of primary form, the primary form
Surface its be intended to refer to the primary shape of the not material by any surface chemical modification or any surface chemical modification
The surface of state, the structure of the device also include elastic clip 15, two opposite clamping limbs 16,21 snap-in locations of the elastic clip 15
Fixed installing is attached in the position of the neighbouring terminal 17 of the micro-fluidic chip, on a clamping limb at least in
There are a miniature ultrasonic transducer units 22, in legend, the miniature ultrasonic transducer units 22 are to attach to be installed on one of folder
In gripping arm 21, and, higher-order of oscillation electric signal transmission cable 23, one end of the higher-order of oscillation electric signal transmission cable 23 is micro- with this
Type ultrasonic transducer 22 links together；The elastic clip 15 provides a function of facilitating the device to disassemble；This is miniature super
Its major function of acoustic wave transducer 22 is in the test of micro-fluidic chip actual sample introduction, and the ultrasonic wave launched using it is reduced
Interfacial tension between the inwall of sample solution and the pipeline, can be compatible, also, using the sample introduction end 18 and
The distance between the terminal 17 and the installation position of miniature ultrasonic transducer units 22 difference and its ultrasonic wave experienced
Difference between difference in intensity, its interfacial tension of sample introduction end 18 described in induced synthesis and the terminal 17 its interfacial tension,
The micro-fluidic chip both ends be interfacial tension difference between sample introduction end 18 and terminal 17 can the micro-fluidic chip this two
End is to form pressure gap between sample introduction end 18 and terminal 17, and the pressure gap can drive sample solution to the direction of terminal 17
Flowing；Its function of miniature ultrasonic transducer units 22 also ultrasonic wave including being launched with it checks biology contained in sample
Its absorption on the inner surface of pipeline of macromolecular, and then check the substrate 19 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 1g of the dimethyl silicone polymer material includes and cover plate 20 and work
Electrode 5, working electrode 6, working electrode 12, working electrode 13 and the micro-fluidic core is together built to electrode 8 and reference electrode 9
Piece, it is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and also include with it to the strong absorption of ultrasonic wave
Property, ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic chip terminal to limited short between the sample introduction end
The rapid decrement of ultrasonic intensity is realized within distance, its locations of structures is located at its core when the actual sample introduction of the micro-fluidic chip is tested
A remaining liquid pool for the terminal that liquid flows is also referred to as terminal liquid pool in piece, is inhaled in the terminal liquid pool filled with some height
Water-resin particle, its opening end of the terminal liquid pool are covered by breathable microporous film.
Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, its try
The flow direction of sample liquid stream.
Miniature ultrasonic transducer units 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.
This case device is that a variety of corresponding cholera antibody are detected with a variety of cholera antigens, thereby cholera diagnosis.
Claims (10)
1. for driving the cholera diagnosis micro fluidic device that the annex of liquid stream can be removed fast, the structure bag of the micro fluidic device
Multichannel micro-fluidic chip is included, the structure of the micro-fluidic chip includes being bonded to each other the substrate and cover plate of installing together, described
Substrate and cover plate are plate object or tablet, and that face towards the cover plate of the substrate is contained via mould pressing process or etching
Technique formed channel structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process,
The window structure that etching technics or simple drilling technology are formed, it is bonded to each other the substrate and the common structure of the cover plate being installed together
The micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto is built up, the locations of structures of the pipeline is located at the base
The interface zone that piece is bonded to each other with the cover plate, its side of the window is blocked by the cover plate and opposite side opens, the knot of the window
Structure position is exactly the locations of structures of the liquid pool, and the quantity of the liquid pool is three, its structure bit set of two liquid pools therein
In the sample introduction end of the micro-fluidic chip, when its locations of structures of a remaining liquid pool is located at the test of the micro-fluidic chip actual sample introduction
The terminal that liquid flows in its chip, the terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is via being similarly positioned in the phase
The manifold shape turnout for the interface zone being mutually bonded respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline with
Positioned at a remaining liquid pool UNICOM for the terminal of the micro-fluidic chip, and, sequentially it is respectively installed in the pipeline
Working electrode on diverse location and to electrode and reference electrode, the working electrode is by conductive electrode and is attached to
The gold size sensitive membrane for having embedded cholera specific antibody on the conductive electrode is formed, and the construction of the pipeline is in parallel construction,
The pipeline in parallel construction is made up of four lateral parallel connections, and the quantity of the working electrode is four, four works
The installation position for making electrode is located in four laterals respectively, and, its top layer gold size of four working electrodes is sensitive
Specific antigen in membrane structure is the four kinds of cholera antigenic substances that can be specifically bound to cholera antibody respectively, four kinds of antigens
Material is cholera TP0821 antigens and cholera TP0319 antigens and cholera TP0624 antigens and cholera O139 antigens respectively,
Its material of the working electrode is gold material or thermal decomposition conducting polymer material, and sheet is presented in its pattern of the working electrode
It is or thread, it is characterised in that its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate 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 micro fluidic device also include elastic clip, two opposite clampings of the elastic clip
Arm snap-in location attaches on the position of the neighbouring terminal of the micro-fluidic chip a, clamping limb at least in
Fixation is equiped with miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, higher-order of oscillation electric signal transmission electricity
One end of cable links together with the miniature ultrasonic transducer units；The elastic clip provides one and facilitates the micro fluidic device to disassemble
Function；Its major function of the miniature ultrasonic transducer units 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 the distance between sample introduction end and the terminal and miniature ultrasonic transducer units installation position difference and it is experienced
Ultrasonic intensity on difference, the difference between its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension
Different, the interfacial tension difference between the micro-fluidic chip both ends can form pressure differential between the both ends of the micro-fluidic chip
Different, the pressure gap can drive sample solution to the end flow；Its function of the miniature ultrasonic transducer units also includes with it
The ultrasonic wave launched checks in sample contained its absorption on the inner surface of pipeline of large biological molecule, and then checks
Swallow up effect of its body phase of the substrate of the dimethyl silicone polymer material to the large biological molecule；The dimethyl silicone polymer material
Its function of the substrate of matter includes with cover plate and working electrode and together builds the micro-fluidic chip to electrode and reference electrode, soft
It is right and the substrate of the dimethyl silicone polymer material its function of having elasticity also includes with its property to the strong absorption of ultrasonic wave
Ultrasonic wave is absorbed strongly, and thereby within micro-fluidic chip terminal to the limited short distance between the sample introduction end
The rapid decrement of ultrasonic intensity is realized, liquid in its chip when its locations of structures is located at the test of the micro-fluidic chip actual sample introduction
A remaining liquid pool for the terminal of flowing is also referred to as terminal liquid pool, and some high hydroscopic resins are filled with the terminal liquid pool
Grain, its opening end of the terminal liquid pool are covered by breathable microporous film.
2. according to claim 1 be used to drive the cholera diagnosis micro fluidic device that the annex of liquid stream can be removed fast,
Characterized in that, the pipeline and the lateral and the manifold shape turnout are capillary channel.
3. according to claim 1 be used to drive the cholera diagnosis micro fluidic device that the annex of liquid stream can be removed fast,
Characterized in that, the thermal decomposition conducting polymer is the conduction formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated
Property material.
4. according to claim 1 be used to drive the cholera diagnosis micro fluidic device that the annex of liquid stream can be removed fast,
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. according to claim 1 be used to drive the cholera diagnosis micro fluidic device that the annex of liquid stream can be removed fast,
Characterized in that, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. according to claim 1 be used to drive the cholera diagnosis micro fluidic device that the annex of liquid stream can be removed fast,
Characterized in that, the cover plate its material in structure is dimethyl silicone polymer material.
7. according to claim 1 be used to drive the cholera diagnosis micro fluidic device that the annex of liquid stream can be removed fast,
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. according to claim 1 be used to drive the cholera diagnosis micro fluidic device that the annex of liquid stream can be removed fast,
Characterized in that, described its thickness of cover plate and substrate in structure is between 1.0 millimeters and 5.0 millimeters.
9. according to claim 1 be used to drive the cholera diagnosis micro fluidic device that the annex of liquid stream can be removed fast,
Characterized in that, the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal passes
Its other end of transmission cable is connected with the higher-order of oscillation electric signal generator.
10. according to claim 1 be used to drive the cholera diagnosis micro fluidic device that the annex of liquid stream can be removed fast,
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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| CN201610627098.2A CN107649205A (en) | 2016-07-26 | 2016-07-26 | The cholera diagnosis micro fluidic device that can be fast removed for the annex for driving liquid stream |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610627098.2A CN107649205A (en) | 2016-07-26 | 2016-07-26 | The cholera diagnosis micro fluidic device that can be fast removed for the annex for driving liquid stream |
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| CN107649205A true CN107649205A (en) | 2018-02-02 |
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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 |
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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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