CN107490702A - The multichannel micro-fluidic chip device of a variety of hypotype swine flus is detected simultaneously - Google Patents
The multichannel micro-fluidic chip device of a variety of hypotype swine flus is detected simultaneously Download PDFInfo
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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Abstract
The present invention relates to a kind of while detect the multichannel micro-fluidic chip device of a variety of hypotype swine flus, belong to analysis testing field.Many obstacles be present using dimethyl silicone polymer i.e. PDMS that is cheap and easily processing come the substrate for making hypotype swine flu diagnosis micro-fluidic chip；The PDMS surfaces are strongly hydrophobic, and surface chemical modification modified effect is difficult to persistently.This case main points are that substrate material is the PDMS for having ecosystem surface, and doped micro-scale titanium dioxide particle is filled with its pipeline of chip；The titanium dioxide granule is the titanium dioxide granule that its surface super hydrophilic property can be induced via advance radiation of visible light；The set in its intergranular super hydrophilic gap road of the titanium dioxide granule filler, it is compensatory, surmounted originally strong hydrophobic pipeline, thus reach constant and super hydrophilic modified effect；The function of the titanium dioxide filler also include taking precautions against chip its pipeline collapse deformation, stop that large biological molecule contacts pipeline internal face.
Description
Technical field
The present invention relates to a kind of while detect the multichannel micro-fluidic chip device of a variety of hypotype swine flus, belong to analysis and survey
Examination field.
Background technology
Multichannel micro-fluidic hypotype swine flu diagnostic techniques background, it is special to may refer to the grade inventions of CN 201110311127.1
Sharp 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 it is etched with the substrate of conduit and the cover plate to fit together therewith, institute
State the fluid course on substrate, before upper cover plate is assembled, it is apparent on see to be exactly some conduits, wait until lid is covered thereon
After piece, just really closure forms the fluid course, and the conduit inner surface of the conduit is together with the part that surround the conduit
Cover plate forms described fluid course together；So, it is clear that assemble the fluid course after completing, its inner surface face
Long-pending major part is the inner surface area of that conduit, and in other words, the state or property of the conduit inner surface are substantially determined
The integrality or property of the fluid course are determined；Therefore say, the inner surface state or interior of this conduit of the structure on substrate
Surface nature is key factor；In principle, any material that can be kept or keep its solid forms substantially, can be used
To make substrate and cover plate, such as, the material that can act as substrate and cover plate can be monocrystalline silicon piece, quartz plate, sheet glass, height
Polymers such as dimethyl silicone polymer, polymethyl methacrylate, makrolon etc.；Certainly, the selection of substrate and the choosing of cover plate
Material be able to can also be differed with identical；From the point of view of material consumption, manufacture difficulty and application popularization prospect etc. etc., these
Not small difference, the especially selection of that substrate between material be present, 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 conduit is made on the substrate of sample, and the lower cost for material, substrate is made with the polydimethyl siloxane material,
Conduit is being suppressed or etched thereon, and is being engaged with the cover plate that the cheap material such as glass or polypropylene or other plastic sheets makes,
It is a kind of more satisfactory selection seemingly；Certainly, patch material can also select to use cheap polydimethyl siloxane material：
So, this substrate selection is the scheme of polydimethyl siloxane material, and material is extremely cheap, and making is extremely simple, seems and should also be as
It is extremely easy to popularize, promotes.
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, conduit is built on this material, if without being operated for the modified of the conduit surface, then, it is whole
After body assembling is completed, that is, after covering cover plate, because the conduit its inner surface in structure occupies most fluid course
Inner surface, then, its strong hydrophobic property of the PDMS conduits inner surface, is deciding factor, it can be similar to water
The fine liquid stream of polar liquid of solution by becoming very difficult, its flow resistance is big, or even in general Micropump is all difficult to
Promote, certainly, if cover plate also selects to use the PDMS material, then, problem is substantially identical, similar；Therefore, existing
Among having technology, modification is modified particular for the conduit inner surface on the PDMS material, is necessary operation；So, this
The individual modified operation for PDMS conduit inner surfaces is pretty troublesomeThat falls nor this problem, forms serious technical puzzlement,
It is another problem：PDMS polymer molecules inside its body phase of this PDMS material substrate have to be diffused to the surface, moves automatically
The characteristic of shifting, the characteristic that this substrate body phase inside PDMS polymer molecules are diffused to the surface, migrated automatically, will cause by table
State after the modification of its inner surface of that conduit of face modifying and decorating can not maintain the sufficiently long time, and that is through surface
Holding time for conduit its inner surface state after modification is substantially only sufficient to the time needs for completing laboratory internal test experiments；
In other words, by surface is modified or the PDMS conduit inner surfaces of surface modification, after it is modified or institute's shape after modification is said
Into surface state can not be lasting, but soon automatically tend to or say become again surface be modified before surface state, compared with
The strong hydrophobic surface state of that script is returned in the short time, then, just think, such micro-fluidic chip can be big
Amount making, mass storage, it is widely popularized, answer is it is obvious that is, impossible.Conduit on this PDMS material, does not do
If surface modification, it can not pump and pass through similar to the fine liquid stream of polar solvent of the aqueous solution, chip also cannot just use；And such as
Fruit has been cooked surface modification, can not persistently keep its state after modifying again, or equally can not popularization and application.
According to the literature, there is a kind of expedient solution, be that a small amount of surface-active is added in sample to be tested solution
Agent, so as to which during test, dynamic, temporary transient effective surface hydrophilic layer is built temporarily in the PDMS conduits inner surface；
However, due to the amphipathic characteristic of surfactant, the introduced surfactant of the program is inevitable simultaneously also can be with sample solution
In tested composition occur combination so that tested composition can not be detected normally or it is detected ratio and dubiously dropped
It is low；The surfactant is possibly even fully wrapped around by tested composition with micelle form so that tested composition can not be detected or
Identification；Therefore, this kind adds the scheme of surfactant into sample solution, is far from a preferable solution.
So, how to accomplish that substrate can either be made using cheap PDMS material, and the conduit can be released
Inner surface decorating state can not persistently, chip can not largely make, largely lay in and then be widely popularized and such a make this area
The puzzlement that numerous professionals 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 conduits inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is known objective
Existing phenomenon.
, 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 channel portion, by chemistry
The conduit inner surface of modification, can contain its absorption to large biological molecule, and then avoid large biological molecule quilt
PDMS substrate body phases are swallowed up；But or that old problem, that is, the chemical modification on PDMS material surface is modified it
Surface state afterwards can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface, migrate automatically
Process, can soon by that by surface chemical modification be modified conduit inner surface state become again script it is strong it is hydrophobic simultaneously
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 substrates its
Conduit inner surface 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 conduit inner surfaces to large biological molecule for a long time, and then prevent PDMS substrate bodies relative
The effect of swallowing up of large biological molecule so that related chip manufactured goods are able to maintain that a prolonged enough, rational shelf-life,
It is exactly a very intractable problem.The problem equally makes this area numerous specially as another problem addressed above
Industry personnel are entangled with, perplexed for a long time, and the problem is equally the highly difficult problem that its obvious technology barrier can not despise.Should
Also be present many year in problem, so far, also not yet properly settled.
Third, the polydimethyl siloxane material, namely PDMS material, the active force very little wherein between polymer molecule,
The polymer molecule of low polymerization degree inside its body phase is in constantly into the dynamic process of surface migration, therefore, includes PDMS
After it has been formed, the surface topography in its inner-walls of duct face of chip can be because of described low polymerization degree polymer point for the chip of substrate material
Son moves about, pours into the surface and change, and the change of its pattern is somewhat similarly to Rheological Deformation, trickling deformation or creep and become
Pattern caused by shape institute is possible changes；In the higher PDMS material of some low polymerization degree component ratios, this kind somewhat similar
Can be showed in the phenomenon of Rheological Deformation, trickling deformation or the deformation of creep must be than more significant；This kind include PDMS substrates chip its
The dynamic of inner-walls of duct surface topography after shaping changes property, namely the described property or stream that are somewhat similarly to Rheological Deformation
Dropping down the property of deformation or the property of the deformation of creep, the word of rheology one is applied mechanically in this case, integration, also referred to as the rheological equationm of state or rheology become
Shape property, the dynamic of corresponding inner-walls of duct face pattern change, and this case is also referred to as rheology；As described above, because of this kind of material
Expect certain Rheological Deformation property as described above that its own has, its manufactured goods actually can at leisure Rheological Deformation and cause
The manufactured goods total form generation changes；Influence caused by its Rheological Deformation property, it is to be not easy to feel in terms of macroscopic perspective
Examine, still, for the very fine micro-fluidic chip of its internal structure, the rheological equationm of state can but cause bigger shadow
Ring, the fluid course namely the pipeline therefore, during pre-production formed, because the wall of its tube chamber of pipeline is main
It is the wall of PDMS materials, so, the cross-sectional area of the pipeline actually can gradually become because of rheology over time
It is small, stated differently, since the reason for the rheology, the natively finer pipeline that is flowed through for liquid sample
Its tube chamber the more can become the more narrow, in the case of flow time is sufficiently long, or even the pipeline tube chamber can partly close or all
Ground closes, and then make it that sample fluid course is thoroughly blocked, and closes with being even also not reaching to its luminal part of pipeline
The degree closed or fully closed, its fluid passage that can be provided of that pipeline narrow because of rheology, then, in pipeline
Its inner surface originally be exactly strongly it is hydrophobic in the case of, aqueous sample liquid is just more difficult to by becoming more so because of rheology
Narrow micro-channel, then, the influence of substrate rheology how is resisted, maintains the basic framework of the pipeline not occur seriously to become for a long time
The problem of shape, also, keep the long-term unobstructed of the pipeline is exactly a urgent need to resolve.
The content of the invention
The technical problem to be solved by the invention is to provide a package solution, solves totally above
The problem for three aspects addressed, also, the solution is applied to hypotype swine flu diagnosis multichannel micro-fluidic chip
Field, form a kind of new hypotype swine flu diagnosis and use multichannel micro-fluidic device.
The present invention solves the technical problem by following scheme, and the device that the program provides is a kind of while detected a variety of
The multichannel micro-fluidic chip device of hypotype swine flu, the structure of the micro fluidic device include multichannel micro-fluidic chip, and this is micro-
The structure of fluidic chip includes being bonded to each other the substrate and cover plate of installing together, and the substrate and cover plate are plate object or piece
The channel structure via mould pressing process or etching technics formation, the base are contained in shape thing, that face towards the cover plate of the substrate
Piece also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or simple drilling technology shape
Into window structure, be bonded to each other the substrate that is installed together and the cover plate be built into jointly containing pipeline configuration and with
Connected liquid pool structure micro-fluidic chip, the locations of structures of the pipeline be located at the interface that the substrate and the cover plate are bonded to each other
Region, its side of the window is blocked by the cover plate and opposite side opens, and the locations of structures of the window is exactly the structure of the liquid pool
Position, the quantity of the liquid pool is three, and its locations of structures of two liquid pools therein is located at the sample introduction end of the micro-fluidic chip, remaining
Under the liquid flowing in its chip when being located at the actual sample introduction test of the micro-fluidic chip of liquid pool its locations of structures terminal, should
Terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is branched off via the manifold shape for being similarly positioned in the interface zone being bonded to each other
Road respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline with positioned at the micro-fluidic chip the terminal
A remaining liquid pool UNICOM, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and right
Electrode and reference electrode, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded hypotype
The gold size sensitive membrane of swine flu specific antigen is formed, and the construction of the pipeline is in parallel construction, the pipeline in parallel construction
It is made up of three lateral parallel connections, the quantity of the working electrode is three, the installation position difference of three working electrodes
In three laterals, and, the specific antigen in its top layer gold size sensitivity membrane structure of three working electrodes
It is the three kinds of hypotype swine flu antigenic substances that can be specifically bound to hypotype swine flu antibody respectively, three kinds of antigenic substance difference
It is hypotype swine flu specific antigen H1N1、H3N2And H1N2, its material of the working electrode is that gold material or thermal decomposition are conductive
Sheet or thread is presented in macromolecule material, the working electrode its pattern, and, Micropump, the Micropump and the micro-fluidic chip
Sample introduction end connects, and the Micropump is the Micropump of external form or the Micropump of built in version, and emphasis is that its material of the substrate is poly- two
Methylsiloxane material, its surface of the substrate are the surfaces of primary form, the surface of the primary form its be intended to refer to and do not have
By any surface chemical modification or the surface of the primary form of the material of any surface chemical modification；And many two
Titan oxide particles, many titanium dioxide granules are filled in the pipeline, and its tube chamber of the pipeline is by many dioxies
Change titanium particle to be filled up, its particle size range of the titanium dioxide granule is between 10 microns and 200 microns, the titanium dioxide granule
It is the titanium dioxide granule by doping vario-property, the titanium dioxide granule is that titanium dioxide content its shared percentage by weight exists
More than 80% particles of inorganic material, the titanium dioxide granule are photic super hydrophilic titanium dioxide granules, the titanium dioxide granule its
Function, which includes it, to form the titanium dioxide granule surface with super hydrophilic property by receiving advance radiation of visible light.
As described above, its composition adulterated of the titanium dioxide granule can be tungsten oxide (WO3), tin oxide (SnO2), five
V 2 O (V2O5), iron oxide (Fe2O3) zinc oxide (ZnO), the silver (Ag) of reduction-state or two or more above-mentioned doping components
Composition；Said composition can be the composition of any ratio of two or more above-mentioned doping components.
Its composition adulterated of the titania particulate material can also include silica (SiO2)。
Titania particulate material described in this case refers to the photic super hydrophilic titania particulate material of visible light-inducing.
Only with regard to the photic super hydrophilic titanic oxide material of various visible light-inducings for itself, for photic super hydrophilic material
It is known for the professional of research field.
Only with regard to the technology of preparing of the photic super hydrophilic titanic oxide material of various visible light-inducings for itself, for photic
It is known for the professional in super hydrophilic investigation of materials field.
Its particle diameter of the titanium dioxide granule can be that the basis between 10 microns and 200 microns is actually needed and any
The particle diameter specified, such as 10 microns, 30 microns, 70 microns, 100 microns, 150 microns or 200 microns of the particle diameter, etc..
The scope of further preferred its particle diameter of the titanium dioxide granule is between 100 microns and 200 microns.
Its pattern of the titanium dioxide granule is unlimited, and the titanium dioxide granule for example can be spheric granules, rod-shaped particles, length
Cube shape particle or any amorphous granular.
The preferred scope of its internal diameter of pipeline is between 500 microns and 1000 microns；It is but excellent compared to above-mentioned
The internal diameter of the pipeline scope of choosing, more tiny internal diameter of the pipeline or thicker internal diameter of the pipeline are also what this case was allowed.
The word of Micropump one art-recognized meanings of itself are known for the professional in micro-fluidic chip field.
The Micropump both can be the Micropump of external form；The Micropump can also do into or say the embedded micro-fluidic chip
The Micropump of the built in version of internal its sample introduction end structure position or the sample introduction end Near-neighbor Structure position, its basic structure key element with it is outer
The Micropump for putting form is identical.
For example miniature piezoelectric pump of the Micropump, miniature peristaltic pump or miniature air driven pump, etc..
Involved Micropump can customize to specialized factory.
Its connected mode with various micro-fluidic chip of various Micropump is known.
Fluid course described in pipeline described in this case and this case, this two kinds to express its art-recognized meanings identical.
The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and hypotype swine flu specific antibody solution
It is even, with point sample instrument point sample or specified structure position is coated on, and form its drying and forming-film.Hypotype in the gold size sensitive membrane
Swine flu specific antibody be horseradish peroxidase or glucose oxidase mark hypotype swine flu antibody, the gold
Glue sensitive membrane has been included as fixing above-mentioned each hypotype swine flu specific antibody and introducing complementary medium therein, the auxiliary
Property medium such as chitosan, cellulose acetate, gelatin be 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 with regard to naked PDMS substrates itself conduit molding or lithographic technique for, be open-and-shut known technology；
Similarly, the technology of hole-opening is even more known simple technique on naked PDMS substrates.This case is not also to this expansion superfluous words.
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..
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.
Its maximum difference in application method of this case micro-fluidic chip and general micro-fluidic chip, is exactly this case miniflow
Control chip its before biological detection operation is applied to, it is necessary in advance with the radiation of visible light micro-fluidic chip its pipeline
The titanium dioxide granule of filling；Because micro-fluidic chip is transparent or translucent state in most cases, and due to
The pipeline is fine enough, and its internal titanium dioxide granule filler is also to belong to finer form, it is seen that light also can
Inject with enough penetrating or partial penetration inject fine titanium dioxide granule filler its entity of the form, therefore, can at this
See in the photic super hydrophilic step of photoinduction, directly with its entirety of the radiation of visible light micro-fluidic chip, it is possible to reach and be directed to
Titanium dioxide granule filler inside its pipeline carries out the effect of radiation of visible light；The photic super hydrophilic step of the visible light-inducing
Suddenly can be a few minutes or several days before using this case micro-fluidic chip progress biological detection or more than ten days or twenties
It is completed.
The light irradiation duration of the radiation of visible light step can be a few minutes to more than ten hour.
The lead of the radiation of visible light step, and, the irradiation duration of the radiation of visible light step is, it is necessary to micro- according to this
The species of specific dopant of the titanium dioxide granule filler filled in fluidic chip, the amount of dopant and specific
Its parameters of preparation process and its super hydrophilic state formed retain duration to determine.
After described advance radiation of visible light step is passed through, remaining specific detection of the micro-fluidic chip makes
With step by hereafter sketching；In other words, hereafter refer to using step and method refer to experienced it is advance described
Remaining operation after radiation of visible light.
This case is flowed with Micropump driving liquid stream in the capillary channel of the triple channel micro-fluidic chip, utilizes multichannel electricity
Chemical analysis instrument is detected to three kinds of hypotype swine flu diagnostic antigens respectively.
Corresponding three kinds of hypotypes swine flu antibody is detected with three kinds of hypotype swine flu antigens, and with three kinds of hypotype swine flus
Antibody detects corresponding three kinds of hypotypes swine flu antigen, similarly, can diagnose corresponding hypotype swine flu；Its foundation
Principle be necessarily antigen, antibody and to be deposited in hypotype swine flu patient, and mutual Reversible binding forms reversible combination
Thing, therefore, detected antibody with antigen and thereby diagnosed corresponding hypotype swine flu, with going to detect antigen with antibody and diagnosing phase
The hypotype swine flu answered, can reach diagnostic purpose.Certainly, its corresponding electrode sensitive decorative layer of different means is in technology
Go up 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 Micropump driving, various hypotype swine flu antibody molecule quilts
The hypotype swine flu for the corresponding horseradish peroxidase-labeled that gold size sensitive membrane embeds is specific on electrode surface in each passage
Antigen capture.
2nd, the hypotype swine flu specific antigen of horseradish peroxidase-labeled resists with the hypotype swine flu in blood serum sample
Body forms immune complex.
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 hypotype swine flu antibody.
It is an advantage of the invention that its scheme of this case is will be all in addition to electrode installation takes up space in the pipeline
Clearance spaces are all filled up with the titanium dioxide granule.Those are filled in the titanium dioxide granule in pipeline, and this case is whole to its
Body abbreviation titanium dioxide granule filler, its function include support, withstand the tube chamber of the pipeline its inwall so that the pipeline
Tube chamber prevents its reduced cross-sectional area of the tube chamber of the pipeline or even closed, so as to tie up for a long time from narrowing because of the rheology
Serious deformation does not occur for the basic framework for holding the pipeline.
Numerous titanium dioxide granule entities are mutually banked up under this case framework together at random in the pipeline, the titanium dioxide
The function of titanium granule filler, having for the titanium dioxide granule for also including living through advance radiation of visible light with it certainly are super
The particle surface of hydrophilic nmature, utilize the mutual institute that is mutually close together by ultra-hydrophilic surface of each adjacent titanium dioxide granule
The complications of formation are continuous and its inner surface has the space of super hydrophilic property, in the pipeline Inner Constitution network morphology
Fluid channel with super hydrophilic property, although the fluid channel with super hydrophilic property that this complications can be continuous all the time,
So, inside the tube chamber of the pipeline simultaneously and a plurality of fluid channel with super hydrophilic property deposited its integrate,
The effect of integrated, cumulative superposition in other words, is the equal of that the relatively fine capillary with Superhydrophilic of caliber leads to
Road；Its presence of the continuous super hydrophilic fluid channel of the complications, its Superhydrophilic to a large extent in other words completely,
Thoroughly overcome, surmounted in degree, counteracting the strong hydrophobic property in its surface of the PDMS substrates of the primary form and made
Into the flow resistance for liquid sample；In other words, it is water that because of liquid sample, it, which accounts for the composition of maximum ratio, liquid sample
It is exactly substantially the aqueous solution, therefore, the presence of the titanium dioxide granule filler can be significantly complete, thorough in other words
Overcome in the degree at bottom with the unmodified PDMS substrates of hydrophobic property and surface its to the aqueous solution it is incompatible, repel and
Barrier effect, so be greatly reduced belong to properties of Aqueous Solution sample liquid stream its be advanced through the resistance of pipeline, its flow
Dynamic resistance be possibly even less than or well below the aqueous solution similar caliber the unorganic glass using silica as main component
Flow resistance in capillary.
Under this case framework, inside the tube chamber of the pipeline, the area of its lumen wall wall of former pipeline, because of described two
The rigid of titan oxide particles filler ties up, the table of part hydrophobic property that still can also be exposed on lumen wall wall
Its area of face is already dramatically reduced, and the area on its still exposed part surface for belonging to hydrophobic property is much
Less than the wall surface area of the hydrophobic property of the lumen wall wall in the presence of no titanium dioxide granule filler；
So, under this case framework, in its lumen of the pipeline, its remaining hydrophobic surface and formed after advance radiation of visible light
Super hydrophilic part increases surface newly, and that it is superimposed, comprehensive, summation, cumulative technique effect, is to form on the whole
In super hydrophilic surface；In other words, inside the tube chamber of the pipeline, the part surface of remaining hydrophobic property its with examination
Interfacial tension between sample solution, plus the super hydrophilic part formed after advance radiation of visible light increase newly surface its with
Interfacial tension between sample solution, that it is superimposed, comprehensive, summation, cumulative technique effect, is so that the pipeline
The synergy of its solid-liquid interfacial tension levels off between its tube chamber inner surface of capillary glass tube and sample solution inside tube chamber
Interfacial tension, it is even lower；In other words, as the above-mentioned interfacial tension in this case of the cumulative technique effect actually
Be level off to the aqueous solution and with super hydrophilic property the surface of solids between that interface interfacial tension.
Therefore, exist in the pipeline under this case framework for having stated titanium dioxide granule filler, in advance to core
In the case that its titanium dioxide filler of piece has carried out radiation of visible light, in other words, it is, because micro-fluidic chip is general
For transparent or semitransparent state is integrally presented, therefore, in the case where having carried out radiation of visible light to chip in advance, based on this
Case scheme, it becomes possible to which the drive to sample liquid stream is reached with extremely low Micropump pump power and extremely low Micropump pumping pressure
It is dynamic.
On the other hand, due to its rheological equationms of state of PDMS as substrate material, it is filled in the pipeline
The titanium dioxide granule filler, can gradually by constantly Rheological Deformation and to arest neighbors free space promote PDMS materials
Pipeline wall more tightly wrap up, this process eventually causes those part titanium dioxides for pressing close to the lumen wall wall
Titanium particle is stuck in original place or is stuck in original place or embedding in-situ titanium dioxide granule and remaining embedded in original place, the part
The titanium dioxide granule banked up with being mutually closely packed together each other incarceration together, due to this reason, the dioxy
Change titanium granule filler just will not move in the pipeline easily, and titanium dioxide granule therein is also substantially all locked
In original place, therefore the stream framework of the micro-fluidic chip can be kept for a long time.
The particle size range of its particle of this case titanium dioxide granule filler between 10 microns and 200 microns, compared to
For general organic molecule, general large biological molecule, the particle diameter of its particle of this case titanium dioxide granule filler can be rated as huge
Greatly, due to its huge particle diameter, and the inner surface of the surface of its polarity and the pipeline of strong hydrophobic PDMS materials can not
Mutually perhaps say and mutually melt, then, the huge titanium dioxide granule of this kind of particle diameter can not be by the pipeline of PDMS materials
Surface is adsorbed, and can not more be swallowed up by the inner surface of the pipeline of PDMS materials, the huge titanium dioxide of this kind of particle diameter
Titanium particle surely not be fully sunk in easily or sink to completely PDMS materials its among intrinsic many Minute pores, and
Because above it is stated that the rheology the reason for, the titanium dioxide granule filler can be stuck in original place in other words it is embedding
In original place without moving easily.
Inside the tube chamber of the pipeline, its lumen wall wall of former pipeline is entirely the surface of hydrophobic property originally, such as
Upper described, under this case framework, rigid because of the titanium dioxide granule filler ties up, on lumen wall wall still also
Its area of the surface of part hydrophobic property that can be exposed is already dramatically reduced, and it is still exposed to belong to hydrophobicity
The area on the part surface of matter has been far smaller than the tube chamber in the presence of no titanium dioxide granule filler
The wall surface area of the hydrophobic property of inwall wall；The reason for because of the rheology, it is close to those dioxies of lumen wall wall
Change titanium particle, be little by little partially embedded into or be partly absorbed among the lumen wall wall, the dioxy among the state
Changing titanium particle, it towards the part surface of lumen wall wall and has occurred and that the lumen wall wall that matching deforms is tight
Closely connected conjunction, then, the matching is deformed and closely pasted with titanium dioxide granule surface having occurred and that in lumen wall wall
The part wall of conjunction actually can not contact with flowing through the sample solution of pipeline, that is to say, that the wall base of this part
In sheet can not suction-operated be produced to the large biological molecule therein that flows through the sample solution of pipeline and organic molecule.Base
In above-mentioned mechanism, then because fill up the pipeline the titanium dioxide granule filler its presence, its tube chamber of the pipeline
The overwhelming majority of inwall wall is tightly covered, and these described walls tightly covered substantially can not be with
Flow through the pipeline sample solution contact, only remaining fraction by titanium dioxide granule, its surface is not pasted closely
The hydrophobic surface close, tightly covered may contact with sample solution, in other words, under this case framework, the life in sample solution
Its direct touch opportunity with hydrophobic PDMS walls of thing macromolecular and organic molecule is significantly reduced, thus, PDMS materials
Its adsorptive hindrance and interference of swallowing up to large biological molecule and organic molecule of lumen wall face is greatly reduced；As above institute
State, this case scheme is advantageous to exclude the adsorptive hindrance and swallows up interference, is advantageous to lift the reliable of correlation analysis test data
Property.
As described above, this case titanium dioxide granule filler, its function actually includes being similar to being directed to PDMS materials
Inner surface of pipeline carry out chemical modification effect, functioning as its this respect is by the inner surface of pipeline of the PDMS materials
By the surface modification of hydrophobic property into the surface of super hydrophilic property, still, with general, usual PDMS surface chemical modifications its
The hydrophilic chemical decorative layer retention time is short, hydrophilic effect can not keep situation prolonged enough different, particle described in this case
The huge titanium dioxide granule filler in footpath, its particle being stuck by rheology can not both be moved easily, its huge particle diameter
Particle can not more be swallowed up easily by the inner-walls of duct of PDMS materials, therefore, its from this respect changes similar to surface chemistry
Seen on the technique effect of property, its technique effect of this case, be form it is permanent, can not erase, can not consume, not be corroded, no
The surface reforming layer with super hydrophilic property being swallowed up, being not dissolved, it is just comparable to one kind in PDMS in effect
The permanent modified surface layer with super hydrophilic property built in its relevant surfaces of base material.
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 in miniflow
Control chip prepare, production, using etc. field play bigger effect.
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
Micropump and other annexes.
In figure, 1,2,8 be the different liquid pool of three installation positions respectively, and 3 be manifold shape turnout, and 4,9,12 be installing respectively
Position is different but three laterals parallel with one another for forming UNICOM's structure in parallel, and 5 be its top layer being installed in lateral 4
Specific antigenic substance in gold size sensitivity membrane structure is hypotype swine flu specific antigen H1N1Working electrode, 10 be installing
The specific antigenic substance in its top layer gold size sensitivity membrane structure in lateral 9 is hypotype swine flu specific antigen
H3N2Working electrode, 11 be the specific antigenic substance in its top layer gold size sensitivity membrane structure being installed in lateral 12
For hypotype swine flu specific antigen H1N2Working electrode, 6 be to electrode, and 7 be reference electrode.
Embodiment
In this case that Fig. 1 is shown embodiment, 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 three liquid pools are liquid pool 1, liquid pool 2, liquid pool 8 respectively, two liquid pools therein
I.e. liquid pool 1 and liquid pool 2 its locations of structures are located at the sample introduction end of the micro-fluidic chip, and a remaining liquid pool is its structure of liquid pool 8
Position is located at the terminal of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested, and the terminal and the sample introduction end are mutual
It is remote, one end of the pipeline via be similarly positioned in the manifold shape turnout 3 of the interface zone being bonded to each other respectively with positioned at sample introduction
Two liquid pools at end are liquid pool 1 and the UNICOM of liquid pool 2, the other end of the pipeline and the terminal positioned at the micro-fluidic chip
A remaining liquid pool is the UNICOM of liquid pool 8, and, be sequentially respectively installed in working electrode in the pipeline on diverse location with
And to electrode and reference electrode, the working electrode is by conductive electrode and the embedding being attached on the conductive electrode
The gold size sensitive membrane of hypotype swine flu 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 three lateral parallel connections, and the quantity of the working electrode is three, the installation position of three working electrodes
Respectively in three laterals, and, the specificity in its top layer gold size sensitivity membrane structure of three working electrodes
Antigen is the three kinds of hypotype swine flu antigenic substances that can be specifically bound to hypotype swine flu antibody respectively, three kinds of antigenic substances
It is hypotype swine flu specific antigen H respectively1N1、H3N2And H1N2, for specific expansion, 5 be its that be installed in lateral 4
Specific antigenic substance in the gold size sensitivity membrane structure of top layer is hypotype swine flu specific antigen H1N1Working electrode, 10 are
The specific antigenic substance being installed in its top layer gold size sensitivity membrane structure in lateral 9 is anti-for hypotype swine flu specificity
Former H3N2Working electrode, 11 be the specific antigen thing in its top layer gold size sensitivity membrane structure being installed in lateral 12
Matter is hypotype swine flu specific antigen H1N2Working electrode, its material of the working electrode be gold material or thermal decomposition lead
Sheet or thread is presented in electric macromolecule material, the working electrode its pattern, and, Micropump, the Micropump and the micro-fluidic chip
Sample introduction end connection, the Micropump is the Micropump of external form or the Micropump of built in version, and emphasis is that its material of the substrate is poly-
Dimethyl siloxane material, its surface of the substrate are the surfaces of primary form, the surface of the primary form its be intended to refer to not
There is the surface of the primary form by any surface chemical modification or the material of any surface chemical modification；It is and many
Titanium dioxide granule, many titanium dioxide granules are filled in the pipeline, and its tube chamber of the pipeline is by the two of many
Titan oxide particles are filled up, and its particle size range of the titanium dioxide granule is between 10 microns and 200 microns, the titanium dioxide
Grain is titanium dioxide granule by doping vario-property, and the titanium dioxide granule is that titanium dioxide content its shared percentage by weight exists
More than 80% particles of inorganic material, the titanium dioxide granule are photic super hydrophilic titanium dioxide granules, the titanium dioxide granule its
Function, which includes it, to form the titanium dioxide granule surface with super hydrophilic property by receiving advance radiation of visible light.
Micropump is depicted without in Fig. 1.
Also the associate members such as multiple tracks electrochemical workstation are depicted without in legend.
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.
The word of Micropump one art-recognized meanings of itself are known for the professional in micro-fluidic chip field.
The Micropump both can be the Micropump of external form；The Micropump can also do into or say the embedded micro-fluidic chip
The Micropump of the built in version of internal its sample introduction end structure position or the sample introduction end Near-neighbor Structure position, its basic structure key element with it is outer
The Micropump for putting form is identical.
For example miniature piezoelectric pump of the Micropump, miniature peristaltic pump or miniature air driven pump, etc..
Involved Micropump can customize to specialized factory.
Its connected mode with various micro-fluidic chip of various Micropump is known.
Claims (9)
1. detecting the multichannel micro-fluidic chip device of a variety of hypotype swine flus simultaneously, the structure of the micro fluidic device includes leading to more
Road micro-fluidic chip, the structure of the micro-fluidic chip include being bonded to each other the substrate and cover plate of installing together, the substrate and
Cover plate is plate object or tablet, and that face towards the cover plate of the substrate is contained via mould pressing process or etching technics shape
Into channel structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etch work
The window structure that skill or simple drilling technology are formed, it is bonded to each other the substrate being installed together and is built into jointly with the cover plate
Micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the locations of structures of the pipeline are located at the substrate with being somebody's turn to do
The interface zone that cover plate is bonded to each other, its side of the window is blocked by the cover plate and opposite side opens, the locations of structures of the window
It is exactly the locations of structures of the liquid pool, the quantity of the liquid pool is three, and it is micro- that its locations of structures of two liquid pools therein is located at this
The sample introduction end of fluidic chip, its locations of structures of a remaining liquid pool are located at its chip when the actual sample introduction of the micro-fluidic chip is tested
The terminal of interior liquid flowing, the terminal are located remotely from each other with the sample introduction end, and one end of the pipeline is bonded to each other via this is similarly positioned in
Interface zone manifold shape turnout respectively with the Liang Ge liquid pools UNICOM positioned at sample introduction end, the other end of the pipeline with positioned at should
A remaining liquid pool UNICOM for the terminal of micro-fluidic chip, and, sequentially it is respectively installed in different positions in the pipeline
The working electrode put and to electrode and reference electrode, the working electrode is by conductive electrode and is attached to the conduction
Property electrode on embedded hypotype swine flu specific antigen gold size sensitive membrane form, the construction of the pipeline is in parallel construction,
The pipeline in parallel construction is made up of three lateral parallel connections, and the quantity of the working electrode is three, three works
The installation position for making electrode is located in three laterals respectively, and, its top layer gold size of three working electrodes is sensitive
Specific antigen in membrane structure is the three kinds of hypotype swine flu antigen things that can be specifically bound to hypotype swine flu antibody respectively
Matter, three kinds of antigenic substances are hypotype swine flu specific antigen H respectively1N1、H3N2And H1N2, its material of the working electrode is
Sheet or thread is presented in gold material or thermal decomposition conducting polymer material, its pattern of the working electrode, and, Micropump should
Micropump is connected with the sample introduction end of the micro-fluidic chip, and the Micropump is the Micropump of external form or the Micropump of built in version, and it is special
Sign is, its material of the substrate is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, the primary shape
The surface of state its be intended to refer to the primary of the not no material by any surface chemical modification or any surface chemical modification
The surface of form；And many titanium dioxide granules, many titanium dioxide granules are filled in the pipeline, described
Its tube chamber of pipeline is filled up by many titanium dioxide granules, its particle size range of the titanium dioxide granule between 10 microns with
Between 200 microns, the titanium dioxide granule is the titanium dioxide granule by doping vario-property, and the titanium dioxide granule is titanium dioxide
Its particles of inorganic material of shared percentage by weight more than 80% of titanium composition, the titanium dioxide granule are photic super hydrophilic titanium dioxides
Titanium particle, its function of the titanium dioxide granule, which includes it, to be formed by receiving advance radiation of visible light with super hydrophilic
The titanium dioxide granule surface of property.
2. multichannel micro-fluidic chip device that is according to claim 1 while detecting a variety of hypotype swine flus, its feature
It is, the pipeline and the lateral and the manifold shape turnout are capillary channel.
3. multichannel micro-fluidic chip device that is according to claim 1 while detecting a variety of hypotype swine flus, its feature
It is, its composition adulterated of the titanium dioxide granule is tungsten oxide (WO3), tin oxide (SnO2), vanadic anhydride (V2O5)、
Iron oxide (Fe2O3) zinc oxide (ZnO), the silver (Ag) of reduction-state or two or more above-mentioned doping components composition.
4. multichannel micro-fluidic chip device that is according to claim 1 while detecting a variety of hypotype swine flus, its feature
Be, the width or diameter of the working electrode between 0.1 micron to 2000 microns, and, the length of the working electrode
Degree is between 1 micron to 15000 microns.
5. multichannel micro-fluidic chip device that is according to claim 1 while detecting a variety of hypotype swine flus, its feature
It is, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. multichannel micro-fluidic chip device that is according to claim 1 while detecting a variety of hypotype swine flus, its feature
It is, the cover plate its material in structure is dimethyl silicone polymer material.
7. multichannel micro-fluidic chip device that is according to claim 1 while detecting a variety of hypotype swine flus, its feature
Be, positioned at the sample introduction end of the micro-fluidic chip two liquid pools its with the remainder positioned at the micro-fluidic chip terminal
A liquid pool between air line distance between 3 centimetres and 7 centimetres；Described its thickness of cover plate and substrate in structure is situated between
Between 1.0 millimeters and 5.0 millimeters.
8. multichannel micro-fluidic chip device that is according to claim 1 while detecting a variety of hypotype swine flus, its feature
It is, its particle size range of the titanium dioxide granule is between 100 microns and 200 microns.
9. multichannel micro-fluidic chip device that is according to claim 1 while detecting a variety of hypotype swine flus, its feature
It is, its inside diameter ranges of the pipeline are between 500 microns and 1000 microns.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610465745.4A CN107490702A (en) | 2016-06-13 | 2016-06-13 | The multichannel micro-fluidic chip device of a variety of hypotype swine flus is detected simultaneously |
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| CN201610465745.4A CN107490702A (en) | 2016-06-13 | 2016-06-13 | The multichannel micro-fluidic chip device of a variety of hypotype swine flus is detected simultaneously |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110394204A (en) * | 2019-08-21 | 2019-11-01 | 苏州大学 | A kind of micro-fluidic chip and preparation method thereof comprising liquid metal electrode |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110394204A (en) * | 2019-08-21 | 2019-11-01 | 苏州大学 | A kind of micro-fluidic chip and preparation method thereof comprising liquid metal electrode |
| CN110394204B (en) * | 2019-08-21 | 2023-09-19 | 苏州大学 | Microfluidic chip containing liquid metal electrode and preparation method thereof |
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