CN107656051A - Its substrate of chip uses the cholera diagnosis micro fluidic device of strong hydrophobic material - Google Patents
Its substrate of chip uses the cholera diagnosis micro fluidic device of strong hydrophobic material Download PDFInfo
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- CN107656051A CN107656051A CN201610626688.3A CN201610626688A CN107656051A CN 107656051 A CN107656051 A CN 107656051A CN 201610626688 A CN201610626688 A CN 201610626688A CN 107656051 A CN107656051 A CN 107656051A
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- 206010008631 Cholera Diseases 0.000 title claims abstract description 67
- 239000000463 material Substances 0.000 title claims abstract description 67
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- 238000003745 diagnosis Methods 0.000 title claims abstract description 22
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- 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
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56911—Bacteria
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- Pathology (AREA)
- Hematology (AREA)
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- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Food Science & Technology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
Cholera diagnosis micro fluidic device the present invention relates to a kind of its substrate of chip using strong hydrophobic material, belongs 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 fastening is positioned at the sample liquid stream terminal of the micro-fluidic chip its neighbor positions manually by the hinge-type fixture for being attached to miniature ultrasonic transducer units, 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 originally hydrophobic capillary channel to the terminal direction.
Description
Technical field
Cholera diagnosis micro fluidic device the present invention relates to a kind of its substrate of chip using strong hydrophobic material, belongs to analysis
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 that a kind of chip its substrate is adopted
With the cholera diagnosis micro fluidic device of strong hydrophobic material, the structure of the micro fluidic device includes multichannel micro-fluidic chip, should
The structure of micro-fluidic chip includes being bonded to each other installing substrate and cover plate together, the substrate and cover plate be plate object or
The channel structure via mould pressing process or etching technics formation is contained in tablet, that face towards the cover plate of the substrate, should
Substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or simple drilling technology
The window structure of formation, be bonded to each other the substrate that is installed together and the cover plate be built into jointly containing pipeline configuration and
The micro-fluidic chip for the liquid pool structure being attached thereto, the locations of structures of the pipeline are located at the boundary that the substrate is bonded to each other with the cover plate
Face 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 knot of the liquid pool
Structure 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,
Its locations of structures of a remaining liquid pool is located at the terminal of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested,
The terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is via the manifold shape for being similarly positioned in the interface zone being bonded to each other
Turnout 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 end
A remaining liquid pool UNICOM at end, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and
To electrode and reference electrode, the working electrode by conductive electrode and the embedding being attached on the conductive electrode suddenly
The gold size sensitive membrane of random specific antigen is formed, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by four
Bar 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 respectively
In four laterals, and, the specific antigen difference in its top layer gold size sensitivity membrane structure of four working electrodes
It is the four kinds of cholera antigenic substances that can be specifically bound to cholera antibody, four kinds of antigenic substances are cholera TP0821 antigens respectively
And cholera TP0319 antigens and cholera TP0624 antigens and cholera O139 antigens, its material of the working electrode is gold
Sheet or thread is presented in material or thermal decomposition conducting polymer material, its pattern of the working electrode, and emphasis is its material of the substrate
Matter is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, the surface of the primary form its be meant to
Be the not primary form of the material by any surface chemical modification or any surface chemical modification surface, the device
Structure also include hinge-type fixture, the hinge-type fixture its appearance profile likeness in form hinge, the hinge-type fixture is by being hinged
Two hinges together and matched through a fastening screw of two hinges and one with the fastening screw and with
What the fastening screw connected together is used for the nut of fastening and hand break loose composition manually, two hinges of the hinge-type fixture
Respectively mutually drawn close with its tip and clamp the micro-fluidic chip, the tip is positioned at the neighbouring terminal of the micro-fluidic chip
Locations of structures on, fixation is attached in a hinge at least in and is equiped with miniature ultrasonic transducer units, and, it is high
Frequency vibration swings electric signal transmission cable, and one end and the miniature ultrasonic transducer units of the higher-order of oscillation electric signal transmission cable are connected to
Together；The hinge-type fixture provides a function of facilitating the device to disassemble；Its major function of the miniature ultrasonic transducer units
Be in the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it reduce sample solution with the pipeline
Interfacial tension between wall, can be compatible, also, is changed using the sample introduction end and the terminal with the miniature ultrasonic
Difference in the distance between energy device installation position difference and its ultrasonic intensity experienced, sample introduction described in induced synthesis
Hold the difference between its interfacial tension and the terminal its interfacial tension, the interfacial tension between the micro-fluidic chip both ends is poor
Different to form pressure gap between the both ends of the micro-fluidic chip, the pressure gap can drive sample solution to the terminal
Flowing；It is big that the ultrasonic wave that its function of the miniature ultrasonic transducer units also includes being launched with it checks biology contained in sample
Its absorption on the inner surface of pipeline of molecule, and then check the substrate of the dimethyl silicone polymer material its body phase to the life
The effect of swallowing up of thing macromolecular；The substrate of the dimethyl silicone polymer material its function includes and cover plate and working electrode and right
Electrode and reference electrode together build the micro-fluidic chip, the substrate of the dimethyl silicone polymer material that is soft and having elasticity its
Function is also included with its property to the strong absorption of ultrasonic wave, and ultrasonic wave is absorbed strongly, and thereby in the micro-fluidic core
The piece terminal is to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end, its structure bit set
A remaining liquid pool for the terminal of liquid flowing is also referred to as eventually in its chip when the micro-fluidic chip actual sample introduction test
Liquid pool is held, is filled with some high hydroscopic resin particles in the terminal liquid pool, its opening end of terminal liquid pool is by breathable microporous film institute
Cover.
Described miniature ultrasonic transducer units can certainly be all installed in two hinges；But only install one
Individual miniature ultrasonic transducer units are dealt with enough to be used.
The word of hinge 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 9000 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 its close position positions the hinge-type folder in the terminal of the micro-fluidic chip
Tool, the miniature ultrasonic transducer units installed with institute's attaching in the hinge-type fixture its hinge, the low-power launched using it, height
The ultrasonic wave of frequent section so that without in strong hydrophobic micro-fluidic chip of surface chemical modification or surface chemical modification
Compatibility between its tube wall of portion's pipeline and the test object aqueous solution is significantly increased, and this is sample liquid stream by providing one
Realistic 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 in the hinge-type fixture its hinge in this case structure, the structure
A function of facilitating the device to disassemble is provided, in this way, the hinge-type fixture is together with miniature ultrasonic appended in its hinge
Transducer just easily can be mutually disengaged with the micro-fluidic chip, then, the component that the part can freely depart from just can be good
Property is re-used cyclically 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 hinge-type is not depicted in the figure
The miniature ultrasonic transducer units set up on fixture and its hinge 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 hinge-type fixture, and 16 indicate linkworks place
Position, 17 be fastening screw, and 18 be higher-order of oscillation electric signal transmission cable, and 19 be miniature ultrasonic transducer units, and 20,25 are respectively
Two different hinges of locations of structures, 21 be cover plate, and 22 be substrate, and 23 be sample introduction end, and 24 be terminal, and 26 be nut；In legend
The hinge-type clamp structure be only signal legend structure, actual its structure of the hinge-type fixture is not limited to the legend hinge-type
Clamp 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 device includes multichannel micro-fluidic chip, should
The structure of micro-fluidic chip includes being bonded to each other the substrate 22 and cover plate 21 of installing together, and the substrate 22 and cover plate 21 are
What is formed via mould pressing process or etching technics contained in plate object or tablet, that face towards the cover plate 21 of the substrate 22
Channel structure, the substrate 22 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 22 being installed together and is built into jointly with the cover plate 21
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 22 is bonded to each other with the cover plate 21, and its side of the window is by this
Cover plate 21 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 23, 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 24 of interior liquid flowing, the terminal 24 are located remotely from each other with the sample introduction end 23, 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 23 and the UNICOM of liquid pool 2, the pipeline
The other end and the remaining liquid pool of the terminal 24 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 antigen 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 antigen in glue sensitivity membrane structure is the four kinds of cholera antigenic substances that can be specifically bound to cholera antibody respectively, and this four
Kind antigenic substance is cholera TP0821 antigens and cholera TP0319 antigens and cholera TP0624 antigens and cholera respectively
O139 antigens, for specifically deploying, 5 be the specificity in its top layer gold size sensitivity membrane structure being installed in lateral 4
Antigenic substance is the working electrode of cholera TP0821 antigens, and 6 be its top layer gold size sensitivity membrane structure being installed in lateral 7
In specific antigenic substance be cholera TP0319 antigens working electrode, 12 be installed in lateral 11 its top layer gold
Specific antigenic substance in glue sensitivity membrane structure is the working electrode of cholera TP0624 antigens, and 13 be to be installed in lateral 14
Specific antigenic substance in its interior top layer gold size sensitivity membrane structure is the working electrode of cholera O139 antigens, the work electricity
Pole 5, working electrode 6, working electrode 12, working electrode 13 its material are gold material or thermal decomposition conducting polymer material, institute
Working electrode 5, working electrode 6, working electrode 12, its pattern presentation sheet or thread of working electrode 13 are stated, emphasis is the substrate
22 its material are dimethyl silicone polymer materials, and its surface of substrate 22 is the surface of primary form, the surface of the primary form
It is intended to refer to not by any surface chemical modification or the table of the primary form of the material of any surface chemical modification
Face, the structure of the device also include hinge-type fixture 15, its appearance profile likeness in form hinge of hinge-type fixture 15, hinge-type folder
Tool 15 by two hinges 20,25 for being mutually hinged and through two hinges 20,25 a fastening screw 17 with
And one matched with the fastening screw 17 and with the fastening screw 17 connect together be used to fasten manually and hand break loose
Nut 26 is formed, and two hinges 20,25 of the hinge-type fixture 15 are respectively mutually drawn close with its tip and clamp the micro-fluidic chip,
The tip is positioned in the locations of structures of the neighbouring terminal 24 of the micro-fluidic chip, a page at least in
Attach to fix on piece and be equiped with miniature ultrasonic transducer units, be to attach to install the miniature ultrasonic in hinge 20 in this legend
Transducer 19, it is of course also possible to allow all to install miniature ultrasonic transducer units in two hinges 20,25, but, generally
Come, one miniature ultrasonic transducer units of installing are attached only in a hinge and are just enough to deal with to be actually needed, and, high frequency
Electric signal transmission cable 18 is vibrated, one end of the higher-order of oscillation electric signal transmission cable 18 connects with the miniature ultrasonic transducer units 19
It is connected together；The hinge-type fixture 15 provides a function of facilitating the device to disassemble；The miniature ultrasonic transducer units 19 its
Major function be in the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it reduce sample solution with it is described
Interfacial tension between the inwall of pipeline, can be compatible, also, using the sample introduction end 23 and the terminal 24 with being somebody's turn to do
Difference in the distance between the installation position of miniature ultrasonic transducer units 19 difference and its ultrasonic intensity experienced, is lured
Lead the difference to be formed between described its interfacial tension of sample introduction end 23 and the terminal 24 its interfacial tension, the micro-fluidic chip this two
End is that the interfacial tension difference between sample introduction end 23 and terminal 24 can be at the both ends of the micro-fluidic chip i.e. sample introduction end 23 and end
Pressure gap is formed between end 24, the pressure gap can drive sample solution to be flowed to the direction of terminal 24；The miniature ultrasonic
The ultrasonic wave that wave transducer 19 its function also includes being launched with it check large biological molecule contained in sample its described
Absorption on inner surface of pipeline, and then check the substrate 22 of the dimethyl silicone polymer material its body phase to the large biological molecule
The effect of swallowing up；Its function of the substrate 22 of the dimethyl silicone polymer material includes and cover plate 21 and working electrode 5, working electrode
6th, working electrode 12, working electrode 13 and the micro-fluidic chip is together built to electrode 8 and reference electrode 9, it is soft simultaneously to have elasticity
The substrate 22 of the dimethyl silicone polymer material its function also include with its property to the strong absorption of ultrasonic wave, to ultrasonic wave
Absorbed strongly, and thereby in the micro-fluidic chip, the terminal 24 is arrived within the limited short distance between the sample introduction end 23 in fact
The rapid decrement of existing ultrasonic intensity, its locations of structures be located at when the actual sample introduction of the micro-fluidic chip is tested liquid flow in its chip
A remaining liquid pool for dynamic terminal 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.
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.
The miniature ultrasonic for being depicted without attaching installing in Fig. 1 in the hinge-type fixture 15 and one hinge changes
Can device 19 and higher-order of oscillation electric signal transmission cable 18；Also, the higher-order of oscillation telecommunication is depicted without in Fig. 1 and Fig. 2
The associate member such as number generator and multiple tracks electrochemical workstation.
Involved hinge-type fixture 15 can be carried out simply cutting using commercially available hinge, changed a social system；The miniature ultrasonic
Transducer 19 is commercially available；Commercially available miniature ultrasonic transducer units are various in style, can select to use as needed；This is miniature super
Acoustic wave transducer 19 can also customize to ultrasonic transducer specialized factory.
Involved higher-order of oscillation electric signal transmission cable 18 is commercially available；Can also be special to ultrasonic transducer producer or cable
Industry producer customizes.
Involved higher-order of oscillation electric signal generator in the 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. its substrate of chip is using the cholera diagnosis micro fluidic device of strong hydrophobic material, the structure of the micro fluidic device is including more
Channel microfluidic chip, the structure of the micro-fluidic chip include being bonded to each other the substrate and cover plate of installing together, the substrate
It is plate object or tablet with cover plate, that face towards the cover plate of the substrate is contained via mould pressing process or etching technics
The channel structure of formation, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etch
The window structure that technique or simple drilling technology are formed, 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 be located at the substrate with
The interface zone that the cover plate is bonded to each other, its side of the window is blocked by the cover plate and opposite side opens, the structure bit of the window
Put be exactly the liquid pool locations of structures, the quantity of the liquid pool is three, and two liquid pools therein its locations of structures was positioned at should
The sample introduction end of micro-fluidic chip, its locations of structures of a remaining liquid pool are located at its core when the actual sample introduction of the micro-fluidic chip is tested
The terminal that liquid flows in piece, the terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is mutually pasted via being similarly positioned in this
The manifold shape turnout of the interface zone of conjunction is respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, and the other end of the pipeline is with being located at
A remaining liquid pool UNICOM for the terminal of the micro-fluidic chip, and, sequentially it is respectively installed in the pipeline different
Working electrode on position and to electrode and reference electrode, the working electrode is by conductive electrode and is attached to this and leads
The gold size sensitive membrane for having embedded cholera specific antibody on conductive electrodes is formed, and the construction of the pipeline is in parallel construction, described
It is made up of in the pipeline of parallel construction four lateral parallel connections, the quantity of the working electrode is four, this four work electricity
The installation position of pole is located in four laterals respectively, and, its top layer gold size sensitive membrane knot of four working electrodes
Specific antigen in structure is the four kinds of cholera antigenic substances that can be specifically bound to cholera antibody respectively, four kinds of antigenic substances
It is cholera TP0821 antigens and cholera TP0319 antigens and cholera TP0624 antigens and cholera O139 antigens respectively, it is described
Its material of working electrode is gold material or thermal decomposition conducting polymer material, and sheet or silk is presented in its pattern of the working electrode
Shape, it is characterised in that its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form,
The surface of the primary form its be intended to refer to not by the material of any surface chemical modification or any surface chemical modification
The surface of the primary form of matter, the structure of the device also include hinge-type fixture, and hinge-type fixture its appearance profile likeness in form is closed
Page, the hinge-type fixture by two hinges being mutually hinged and a fastening screw through two hinges and
One matches with the fastening screw and is used for the nut structure of fastening and hand break loose manually with what the fastening screw connected together
Into two hinges of the hinge-type fixture are respectively mutually drawn close with its tip and clamp the micro-fluidic chip, and the tip is positioned at
Fixed installing is attached in the locations of structures of the neighbouring terminal of the micro-fluidic chip, in a hinge at least in
There are 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
Linked together with the miniature ultrasonic transducer units；The hinge-type fixture provides a function of facilitating the device to disassemble；Should
Its major function of miniature ultrasonic transducer units be in the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it come
Reduce the interfacial tension between the inwall of sample solution and the pipeline, can be compatible, also, using the sample introduction end with
And the distance between the terminal and the miniature ultrasonic transducer units installation position difference and its ultrasonic wave experienced it is strong
Difference between difference on degree, its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension, the miniflow
Interfacial tension difference between the control chip both ends can form pressure gap between the both ends of the micro-fluidic chip, the pressure
Difference can drive sample solution to the end flow；Its function of the miniature ultrasonic transducer units also includes surpassing with what it was launched
Sound wave checks in sample contained its absorption on the inner surface of pipeline of large biological molecule, and then checks the poly dimethyl
Swallow up effect of its body phase of the substrate of siloxanes 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
Its function of the substrate of the dimethyl silicone polymer material is also included with its property to the strong absorption of ultrasonic wave, and ultrasonic wave is carried out
It is strong to absorb, and thereby realize ultrasonic wave within micro-fluidic chip terminal to the limited short distance between the sample introduction end
The rapid decrement of intensity, its locations of structures are located at the terminal of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested
A remaining liquid pool be also referred to as terminal liquid pool, is filled with some high hydroscopic resin particles, the terminal in the terminal liquid pool
Its opening end of liquid pool is covered by breathable microporous film.
2. for its substrate of chip according to claim 1 using the cholera diagnosis micro fluidic device of strong hydrophobic material, it is special
Sign is that the pipeline and the lateral and the manifold shape turnout are capillary channel.
3. for its substrate of chip according to claim 1 using the cholera diagnosis micro fluidic device of strong hydrophobic material, it is special
Sign is that the thermal decomposition conducting polymer is the electric conductivity material formed by polyimides or polyacrylonitrile after anoxybiotic is heat-treated
Material.
4. for its substrate of chip according to claim 1 using the cholera diagnosis micro fluidic device of strong hydrophobic material, it is special
Sign is, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the working electrode
Length is between 1 micron to 15000 microns.
5. for its substrate of chip according to claim 1 using the cholera diagnosis micro fluidic device of strong hydrophobic material, it is special
Sign is that the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. for its substrate of chip according to claim 1 using the cholera diagnosis micro fluidic device of strong hydrophobic material, it is special
Sign is, the cover plate its material in structure is dimethyl silicone polymer material.
7. for its substrate of chip according to claim 1 using the cholera diagnosis micro fluidic device of strong hydrophobic material, it is special
Sign is, positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with positioned at the micro-fluidic chip terminal this is remaining
Under a liquid pool between air line distance between 3 centimetres and 7 centimetres.
8. for its substrate of chip according to claim 1 using the cholera diagnosis micro fluidic device of strong hydrophobic material, it is special
Sign is that described its thickness of cover plate and substrate in structure is between 1.0 millimeters and 5.0 millimeters.
9. for its substrate of chip according to claim 1 using the cholera diagnosis micro fluidic device of strong hydrophobic material, it is special
Sign is that the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission electricity
Its other end of cable is connected with the higher-order of oscillation electric signal generator.
10. for its substrate of chip according to claim 1 using the cholera diagnosis micro fluidic device of strong hydrophobic material, it is special
Sign is that for its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units between 5 milliwatts and 9000 milliwatts, this is miniature super
The frequency of its ultrasonic wave operationally launched of acoustic wave transducer is between 100KHz and 12MHz.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101561444A (en) * | 2008-04-18 | 2009-10-21 | 中国科学院大连化学物理研究所 | Micro-fluidic chip with an integrated PDMS surface tension minipump and application thereof |
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