CN106990241A - The special cheap AIDS diagnosis micro fluidic device of fluid type of drive - Google Patents
The special cheap AIDS diagnosis micro fluidic device of fluid type of drive Download PDFInfo
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- CN106990241A CN106990241A CN201610065953.5A CN201610065953A CN106990241A CN 106990241 A CN106990241 A CN 106990241A CN 201610065953 A CN201610065953 A CN 201610065953A CN 106990241 A CN106990241 A CN 106990241A
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- 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
- G01N33/56983—Viruses
- G01N33/56988—HIV or HTLV
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Abstract
The present invention relates to a kind of special cheap AIDS diagnosis micro fluidic device of fluid type of drive, belong to analysis testing field.It is a technical goal to make AIDS diagnosis with the substrate of micro-fluidic chip with dimethyl silicone polymer i.e. PDMS that is cheap and easily processing；But, its surface of the material is strongly hydrophobic, and targetedly surface is modified or surface modification, and its effect is 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 its neighbor positions attaches installing miniature ultrasonic transducer units in the test liquid stream terminal of the micro-fluidic chip, ultrasonic wave damper is installed at the sample introduction end of the micro-fluidic chip, reach ultrasonic intensity rapid decrement in short distance, and interfacial tension difference is thus formed at the two ends of the chip, the interfacial tension difference causes the two ends to form pressure differential, and the pressure differential drives test liquid stream to be flowed along capillary channel to the terminal direction.
Description
Technical field
The present invention relates to a kind of special cheap AIDS diagnosis micro fluidic device of fluid type of drive, the micro fluidic device is
Based on antigen/antibody specific reaction come the special purpose device of diagnosis of aids, belong to analysis testing field.
Background technology
The micro-fluidic AIDS diagnosis technical background of associated multi-channel, may refer to the patent of invention such as CN 200910151219.0 Shen
Please case.
Only for the microflow control technique overall general picture of itself, it may refer to famous micro-fluidic expert Mr. Lin Ping Cheng and go out not long ago
Monograph " diagram Microfluid based Lab on a chip ", the monograph is published via Science Press, and the monograph is to microflow control technique
Past, now, and, in terms of vision of the future 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 small fluid course and the cover plate fit together therewith,
Small fluid course on the substrate, assembling upper cover plate before, it is apparent on see to be exactly some micro-channels, wait until thereon
After covering cover plate, just real closure forms the small fluid course, and the conduit inner surface of the micro-channel is together with surround this
The part cover plate of micro-channel constitutes described small fluid course together；So, it is clear that this after assembling is completed is small
Fluid course, the major part of its inner surface area is the inner surface area of that micro-channel, in other words, in the micro-channel
The state or property on surface substantially determine the integrality or property of the small fluid course；Therefore say, this is built in base
The inner surface state or inner surface property of micro-channel on piece are key factors；In principle, it is any to keep or protecting substantially
The material of its solid forms is held, can be used to make substrate and cover plate, such as, the material that can act as substrate and cover plate can be with
It is monocrystalline silicon piece, quartz plate, sheet glass, high polymer such as dimethyl silicone polymer, polymethyl methacrylate, makrolon etc.
Deng；Certainly, the selection of substrate and the selection of cover plate be able to can also be differed with identical；From material consumption, manufacture difficulty and
From the point of view of in terms of application popularization prospect etc., between these materials exist not small difference, the especially selection of that substrate, influence compared with
Greatly.
In various substrate making materials, dimethyl silicone polymer, i.e. PDMS, comparatively very easily shaping, so
Substrate on make that micro-channel is extremely simple, and the lower cost for material makes substrate with the polydimethyl siloxane material,
Micro-channel 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, makes 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 the letter PDMS that abridges is referred to, itself are a kind of strong
Hydrophobic material, micro-channel is built on this material, if without being operated for the modified of the micro-channel surface, then,
After overall assembling is completed, that is, cover after cover plate, because the micro-channel its inner surface in structure occupies most liquid circulation
The inner surface in road, then, its strong hydrophobic property of the PDMS micro-channels inner surface, is deciding factor, it can cause class
Be similar to the aqueous solution the fine liquid stream of polar liquid by becoming very difficult, its flow resistance is big, or even general Micropump is all
It is 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
Operation；So, this is pretty troublesome for the modified operation of PDMS micro-channel inner surfacesThat falls nor this problem, structure
Perplex into serious technical, be another problem：PDMS polymer molecules tool inside its body phase of this PDMS material substrate
There are PDMS polymer molecules inside the characteristic for diffusing to the surface, migrating automatically, this substrate body phase to diffuse to the surface, move automatically
The characteristic of shifting, will cause the state after modification by its inner surface of that micro-channel of surface modifying and decorating can not maintain foot
Enough long time, the holding time for micro-channel its inner surface state after that is surface-modified is substantially only sufficient to complete in laboratory
The time of portion's test experiments needs；In other words, by surface modification or the PDMS micro-channel inner surfaces of surface modification, its
The surface state that is formed can not be lasting after modification or after saying modification, but soon automatically tend to or say and become surface again and change
Surface state before property, returns to the strong hydrophobic surface state of that script in the shorter time, then, just think,
Such micro-fluidic chip can largely make, mass storage, be widely popularized, and answer is it is obvious that is, impossible.
Micro-channel on this PDMS material, can not pump similar to the fine liquid stream of polar solvent of the aqueous solution if not doing surface modification
Send and pass through, chip also cannot just be used；And if having done surface modification, the state after its modification can not be persistently kept again, also
Being equally can not popularization and application.
So, how to accomplish that substrate can either be made using cheap PDMS material, and table in the micro-channel can be released
Face decorating state can not persistently, chip can not largely make, largely lay in so that be widely popularized it is such a make this area it is numerous specially
The puzzlement that industry personnel 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, above it is stated that, its surface is strongly hydrophobic, this strong hydrophobic
Material surface and also 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 gradually deep, directly
It is trapped in heavy within the body phase of PDMS substrates, in fact, this process is partly also due to inside PDMS material body phase
Polymer molecule, which has, to be diffused to the surface, caused by travel motion；Such case, can also be explained from another angle, i.e.
Continuously from inside PDMS body phases to its diffusion into the surface, migration those polymer molecules, its result moved, be by
Gradually those are involved within the body phase of PDMS substrates by the large biological molecule of adsorption, briefly, these are inhaled
Attached large biological molecule is exactly to be swallowed up by PDMS substrate body phases；So, this PDMS substrates body phase swallows up large biological molecule
Phenomenon, the influence caused by it necessarily causes the severe deviations of all kinds of test data of experiment for being related to large biological molecule.
As described above, be the problem of PDMS substrates, its not only adsorption large biological molecule, and swallow up large biological molecule,
So, as the large biological molecule of experiment test object, its disappearance will not stop because the absorption of surface saturation, but, no
It is disconnected adsorbed, also constantly swallowed up.
On PDMS substrates in related experiment test process its body phase constantly swallow up test associated biomolecule macromolecular phenomenon, separately
It is to say that one kind, which is explained, there are substantial amounts of Minute pores in PDMS body phases, and associated biomolecule macromolecular is by after adsorption, depression
Into these Minute pores, and then swallowed up；However, inventor thinks, those can allow the air point of miniature scale
Son squeezes into the Minute pores therebetween, and being not equal to them also can directly allow that the large biological molecule of relative large scale enters, and two
Person's difference on yardstick is huge, must not make sweeping generalizations.Explanation is bypassed, in any case, the biology of object is analyzed as dependence test
Macromolecular is adsorbed by PDMS substrate micro-channels inner surface, and then is constantly swallowed up by PDMS substrate body phases, and this is known objective
The phenomenon of presence.
, can be from containment PDMS surfaces to life in order to prevent this PDMS substrate bodies relative to the effect of swallowing up of large biological molecule
The absorption of thing macromolecular is addressed, 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 quilt
PDMS substrate body phases are swallowed up；But, or that old problem, that is, the chemical modification on PDMS material surface changes
Surface state after property can not persistently be kept, the polymer molecule inside the PDMS substrate body phases its diffuse to the surface automatically,
The process of migration, 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
Its micro-channel inner surface of substrate 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, can reach again
Growth stage contains absorption process of the PDMS substrate micro-channel inner surfaces to large biological molecule, and then prevents PDMS substrate body phases
The effect of swallowing up to 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 makes the numerous specialties in this area as another problem addressed above, equally
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.The hardly possible
Also be present many year in topic, so far, also not yet properly settled.
The content of the invention
The technical problems to be solved by the invention are to provide a package solution, solve what is addressed above totally
Two problems, also, the solution is used into multichannel micro-fluidic chip field applied to AIDS diagnosis, form a kind of new
AIDS diagnosis multichannel micro-fluidic device.
The present invention solves the technical problem by following scheme, and the device that the program is provided is that a kind of fluid type of drive is special
Cheap AIDS diagnosis micro fluidic device, the structure of the micro fluidic device includes multichannel micro-fluidic chip, and this is micro-fluidic
The structure of chip includes installing substrate and cover plate together bonded to each other, and the substrate and cover plate are plate object or tablet,
The channel structure via mould pressing process or etching technics formation is contained in that face towards the cover plate of the substrate, and the substrate also contains
It is connected and pierces the window knot via the formation of mould pressing process, etching technics or simple drilling technology of the substrate with the channel structure
Structure, substrate bonded to each other being installed together has been built into containing pipeline configuration and the liquid pool being attached thereto jointly with the cover plate
The micro-fluidic chip of structure, the locations of structures of the pipeline is located at the substrate and cover plate interface zone bonded to each other, the window its
Side is blocked by the cover plate and opposite side is opened, and the locations of structures of the window is exactly the locations of structures of the liquid pool, the liquid pool
Quantity 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 knot of a remaining liquid pool
Structure 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 of the interface zone bonded to each other respectively with positioned at sample introduction end
The Liang Ge liquid pools UNICOM, the other end of the pipeline and a remaining liquid pool for the terminal positioned at the micro-fluidic chip join
It is logical, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode and reference electrode is described
Working electrode is sensitive by conductive electrode and the gold size for having embedded AIDS specific antibody being attached on the conductive electrode
Film is constituted, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of four lateral parallel connections, described
The quantity of working electrode is four, and the installation position of four working electrodes is located in four laterals respectively, and,
Specific antibody in the sensitive membrane structure of its top layer gold size of four working electrodes is that AIDS antigen can be specifically bound respectively
Four kinds of aids antibody materials, four kinds of antibody materials be respectively aids antibody p24 and aids antibody gp41 and
Aids antibody gp120 and aids antibody gp36, its material of the working electrode is that gold material or thermal decomposition are conductive high
Sheet or thread is presented in molecule material, its pattern of the working electrode, and emphasis is that its material of the substrate is dimethyl silicone polymer
Material, its surface of the substrate is the surface of primary form, the surface of the primary form its be intended to refer to not pass through any surface
The surface of the primary form of the material of chemical modification or any surface chemical modification, the structure of the micro fluidic device is also including miniature
Ultrasonic transducer, and, higher-order of oscillation electric signal transmission cable, one end of the higher-order of oscillation electric signal transmission cable is micro- with this
Type ultrasonic transducer links together, and the miniature ultrasonic transducer units are installed in the cover plate or substrate of the micro-fluidic chip with attaching
The neighbouring terminal position；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 reduces the interfacial tension between sample solution and the inwall of the pipeline, can be compatible,
Also, using the distance between the sample introduction end and the terminal and miniature ultrasonic transducer units installation position difference and its
The difference on ultrasonic intensity experienced, its interfacial tension of sample introduction end described in induced synthesis and the terminal its interfacial tension it
Between difference, the interfacial tension difference between the micro-fluidic chip two ends can form pressure between the two ends of the micro-fluidic chip
Power difference, the pressure gap can drive sample solution to the end flow；The miniature ultrasonic transducer units its functions also include with
Its ultrasonic wave launched checks in sample contained large biological molecule its absorption on the inner surface of pipeline, and then checks
Swallow up effect of its body phase of the substrate of the dimethyl silicone polymer material to the large biological molecule；The dimethyl silicone polymer material
Substrate its function include with cover plate and working electrode and electrode and reference electrode together built the micro-fluidic chip, it is soft simultaneously to have
The substrate of the dimethyl silicone polymer material its function of elasticity is also included with its property to the strong absorption of ultrasonic wave, to ultrasonic wave
Absorbed strongly, and ultrasound is thereby realized within micro-fluidic chip terminal to the limited short distance between the sample introduction end
The rapid decrement of intensity of wave；And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or bar-shaped；Should
Its material of ultrasonic wave damper is microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip, the elastic clip
There are two clamping limbs, the medial surface of each clamping limb is relative with the medial surface of another clamping limb, the inner side of one of clamping limb
The sample introduction end of the micro-fluidic chip is close in face, and the medial surface of another clamping limb is close to the ultrasonic wave damper, the elastic clip
With its gripping strength by the sample introduction end of the micro-fluidic chip and the ultrasonic wave damper it is bonded to each other clip together, the ultrasonic wave disappears
Subtract the strong consumption to ultrasonic energy that device is brought with its material, further support that the terminal is arrived in the micro-fluidic chip
The rapid decrement of ultrasonic intensity is realized within limited short distance between the sample introduction end, and thereby further expands the sample introduction
Hold the difference between its interfacial tension and the terminal its interfacial tension.
The gold size sensitive membrane is to be sufficiently mixed chitosan gold size solution and AIDS specific antibody solution uniformly, uses point sample
Instrument point sample is coated on specified structure position, and forms its drying and forming-film.AIDS disease-specific in the gold size sensitive membrane resists
Body is the aids antibody of horseradish peroxidase or glucose oxidase mark, and the gold size sensitive membrane has been included as fixing
Above-mentioned each AIDS specific antibody and introduce complementary medium therein, the complementary medium such as chitosan, acetate fiber
Element, gelatin is therein a kind of or their mixture.
The pipeline and the lateral and the manifold shape turnout in the microfluidic chip structure, its internal diameter chi
It is very little to may each be arbitrarily selected size, still, use the consideration in terms of prepare liquid sample and reduction reagent loss less for trying one's best,
The passage of capillary level, the capillary level are preferably selected in the pipeline and the lateral and the manifold shape turnout
Passage imply that its internal diameter passage suitable with the internal diameter of the capillary on ordinary meaning.Its inner passage of capillary it is transversal
Face shape can be arbitrary shape, the shape of cross section is for example circular, oval, square, rectangle, bar shaped, certainly
Can be arbitrarily exist bending it is linear, also, the capillary interior shape with the extension of pipeline, different parts
Shape of cross section can also allow to be different shapes.Only for the word of capillary one, its art-recognized meanings is known.
What is be related in structure is the electrode of microsize to electrode and reference electrode, and its electrode shape may each be any choosing
Fixed shape, the arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..It is described to electricity
The art-recognized meanings of pole 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 scrotiform structure for transitional liquid storage
Make, its shape of the inner chamber of each liquid pool may each be arbitrarily selected shape, the cavity shape such as cylindrical empty
Cavity-like, square column type cavity-like, oblong cavity shape or spherical hollow space shape etc..The size of the liquid pool can be arbitrarily selected
Size, still, in order to use prepare liquid sample and reduction reagent loss less as far as possible, the liquid pool is preferably capable of and capillary
The liquid pool of the microminiature of matching.
It is public only for professional of the word of ultrasonic transducer one art-recognized meanings of itself for ultrasonic technology field
Know.
Various sizes, variously-shaped ultrasonic transducer are commercially available；Commercially available miniature ultrasonic transducer units its sizes can be with
It is small 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 itself and
Speech, is known general technology for the professional in ultrasonic technology field.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 technology；Together
Sample, 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.
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 transmission electricity
Its other end of 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, for the professional in ultrasonic technology field, be
It is simple and known；The higher-order of oscillation electric signal generator can be customized to ultrasonic instrument specialized factory.
The preferred scope of its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units be between 2 milliwatts and 2000 milliwatts it
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.
This case device can further include some annexes, the annex such as multiple tracks electrochemical workstation etc., institute certainly
The art-recognized meanings for stating multiple tracks electrochemical workstation are known.Each working electrode for being related in this case microfluidic chip structure and
, can be respectively via corresponding special the corresponding interface got lines crossed with the multiple tracks electrochemical workstation to electrode and reference electrode etc.
Coupled.It is described that special to get lines crossed be for each the corresponding interface of each electrode and the multiple tracks electrochemical workstation is carried out into phase
The private cable being mutually coupled with.The micro-fluidic chip in this case device, its structure can also include micro-valve, the number of the micro-valve
Amount is not limited, according to actual needs, and the micro-valve can be installed in any required position installed in the microfluidic chip structure；
The word of micro-valve one is for the professional of micro fluidic chip technical field, and the art-recognized meanings of itself are known；The micro-valve
The manufacturing technology of itself 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, it is however recommended to
Or say preferred its scope of the diameter between 0.1 micron to 2000 microns；The length of the working electrode can permit
Permitted to be that any setting is easily installed the length used, it is however recommended to or to say preferred its scope of the length be at 1 micron
To between 15000 microns.
The gold size for being installed in the working electrode surface layer by spraying or point sample instrument point sample or the coating of other appropriate process is quick
Feel film, its thicknesses of layers can allow be any setting treat sample measuring liquid occur electrical signals response thickness, still, push away
Preferred thickness is between 10 nanometers and 200 nanometers in other words for the thickness recommended.
The cover plate in chip structure, its material can allow to be any electrical insulating property material, for example：Polypropylene, glass
Glass, polymethyl methacrylate, dimethyl silicone polymer, etc., in order to make smaller size of micro-fluidic chip, such as do
Realized into the micro-fluidic chip of only 2.0 centimetres to 3.0 centimetres of super-small of length, and 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
It is used as the cover plate using dimethyl silicone polymer, is also that 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 this is remaining
Air line distance between one liquid pool can be arbitrarily selected suitable distance as needed, and still, the preferred value of the distance is
Between 3 centimetres and 7 centimetres.
Described its thickness of cover plate and substrate can allow be any setting be easy to assembling thickness, the thickness of recommendation or say preferably
Thickness be between 1.0 millimeters and 5.0 millimeters.Less thickness is conducive to saving material.
Described its size of ultrasonic wave damper is not limited, and described its length of ultrasonic wave damper, width, thickness may each be basis
Need the arbitrary size of setting.
It is known in field of rubber technology only for the word of microcellular rubber one art-recognized meanings of itself.
The microcellular rubber is commercially available.
It is known in field of rubber technology only for the word of sponge rubber one art-recognized meanings of itself.
The sponge rubber is commercially available.
It is known in technical field of macromolecules only for the word of microporous polyurethane elastomer one art-recognized meanings of itself.
The polyurethane micropore elastomer material is commercially available.
The microcellular rubber preferred microporous silicon rubber or micropore fluorubber.
It is known in field of rubber technology only for the word of micropore silicon rubber one art-recognized meanings of itself.
The microporous silicon Rubber market is on sale.
It is known in field of rubber technology only for the word of micropore fluorubber one art-recognized meanings of itself.
The micropore fluorubber is commercially available.
The word of elastic clip one art-recognized meanings of itself are known.
The elastic clip is commercially available.
The application method of this case micro-fluidic chip：
Proposed first based on this case and the first public New stream driving principle, its application running of this case micro-fluidic chip
In, the New stream driving method is determined completely without involving any additional Micropump.
The interfacial tension difference of this case to be formed between micro-fluidic chip two ends caused by the ultrasonic wave, drives liquid
Stream flows in the capillary channel of the four-way micro-fluidic chip, using four-way electrochemical analytical instrument respectively to four kinds of AIDS
Sick diagnostic antigen is detected.
The specific detection of this case micro-fluidic chip is as follows using step：
1st, blood serum sample liquid is added in micro-pipe road, under ultrasonic wave driving, various AIDS antigen molecules are by each passage
The AIDS specific antibody capture for the corresponding horseradish peroxidase-labeled that gold size sensitive membrane is embedded on middle electrode surface.
2nd, the AIDS antigen in the AIDS specific antibody and blood serum sample of horseradish peroxidase-labeled forms immune compound
Thing.
3rd, using multi-channel electrochemical analyzer, the electron mediators such as catechol are added, using the above-mentioned reaction of amperometric detection
Caused curent change, is derived from the species and content of various analytes.
4th, result is subjected to comprehensive analysis, comprehensive diagnos is carried out to AIDS antigen.
Changed it is an advantage of the invention that installing miniature ultrasonic in its close position attaching of the terminal of the micro-fluidic chip
Can device, it is launched using the miniature ultrasonic transducer units low-power, the ultrasonic wave of high-frequency band so that without coming to the surface
The compatibility learned between strong hydrophobic its tube wall of micro-fluidic chip internal pipeline and the test object aqueous solution of modification significantly increases
Plus, this is test liquid stream by there is provided a realistic possibility；Meanwhile, using dimethyl silicone polymer substrate its to ultrasound
The strong absorbability of ripple, in shorter distance, it is, from the terminal to only several centimeters the sample introduction end
In the very short distance of yardstick, reach the rapid decrement of ultrasonic intensity, thereby cause institute at the two ends of the micro-fluidic chip
The difference of interfacial tension is stated, and then, utilize the pressure between its two ends for being formed of the difference of the interfacial tension between the two ends
Difference, driving test liquid stream flows in the strong hydrophobic capillary channel of such a script to the terminal direction.By this
Case liquid stream drive scheme, entirely without any come to the surface must be carried out to the substrate and its internal pipeline of the dimethyl silicone polymer material
Modification or chemical modification are learned, the laborious procedures of the surface chemical modification or chemical modification have been altogether dispensed with；And altogether dispense with biography
The equipment of Micropump in meaning of uniting etc；On the other hand, the ultrasonic wave of the low-power, high-frequency band, additionally it is possible to contain in sample
Absorption of the large biological molecule on literalness naked its inner surface of pipeline of dimethyl silicone polymer substrate, and then contain that this gathers
Swallow up effect of its body phase of dimethyl siloxane piece to the large biological molecule；The antigen, antibody and antigen and antibody
Reversible binding thing is all the type for belonging to described large biological molecule certainly；Due to described suction-operated and the described work that swallows up
With effectively being contained, therefore, dependence test result will be better able to objectively reflect actual conditions；The low-power, height are again and again
The effect of section ultrasonic wave, also includes facilitating what the Reversible binding between antigen, antibody react quickly to reach, this causes correlation certainly
Test operation can be with than the completion of faster speed.
Due to the surface chemical modification for the dimethyl silicone polymer substrate its relevant surfaces or chemical modification behaviour need not be carried out
Make, therefore, this surface chemical modification layer or chemically modified layer not need to exist, then, the dimethyl silicone polymer
Its body phase interior polymer molecule of substrate constantly diffuses to the surface automatically, migrate caused by it to surface chemical modification layer or
The damaging influence of chemically modified layer is also just not present.
This case its installation position is located at the ultrasonic wave damper at the sample introduction end, from its terminal of this case micro-fluidic chip to
Said on the sport technique segment that ultrasonic intensity rapid decrement is realized in the such short distance in sample introduction end, its effect of the ultrasonic wave damper is suitable
In the size expansion device of micro-fluidic chip, in other words, the ultrasonic wave damper its function as and significantly extend miniflow
Its terminal of chip is controlled the distance between to sample introduction end, is the equal of from several centimetres of extension of script to more than ten centimetres of length
Or twenties centimetres of length or longer length, so so that described terminal to the ultrasonic wave between sample introduction end in short distance
The sport technique segment of intensity rapid decrement can relatively easily be reached, also, the size expansion device namely the ultrasonic wave damper
Demolition, installation are convenient, it is important that it can also be reused.
The technical scheme of this case has dissolved its application related one to dimethyl silicone polymer substrate addressed above totally
Row technical barrier.Based on this case scheme, this kind very cheap polydimethyl siloxane material is just possible in the micro-fluidic 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 is bowed
Do not depicted in the structural form of chip internal pipeline and each electrode and each related liquid pool under angle, the figure described miniature super
Acoustic wave transducer 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, 4,7,11,14
It is that installation position is different but four laterals parallel with one another for forming UNICOM's structure in parallel respectively, 5 be to be installed in lateral 4
The working electrode that specific antibody material in the interior sensitive membrane structure of its top layer gold size is AIDS specific antibody p24,6 are
Specific antibody material in the sensitive membrane structure of its top layer gold size being installed in lateral 7 is AIDS specific antibody
Gp41 working electrode, 12 be the specific antibody thing in the sensitive membrane structure of its top layer gold size being installed in lateral 11
Matter is AIDS specific antibody gp120 working electrode, and 13 be that its top layer gold size being installed in lateral 14 is sensitive
The working electrode that specific antibody material in membrane structure is AIDS specific antibody gp36,8 be that, to electrode, 9 be reference
Electrode, 15 be the substrate of dimethyl silicone polymer material, and 16 be cover plate, and 17 be higher-order of oscillation electric signal transmission cable, 18
It is miniature ultrasonic transducer units, 19 be the sample introduction end of the micro-fluidic chip, and 20 be the terminal of the micro-fluidic chip；
Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, the stream of its test liquid stream
Dynamic direction.
Embodiment
In this case that Fig. 1 and Fig. 2 are shown embodiment, the structure of the micro fluidic device includes multichannel micro-fluidic chip,
The structure of the micro-fluidic chip includes the substrate 15 and cover plate 16 of installing bonded to each other together, the substrate 15 and cover plate 16
It is plate object or tablet, that face towards the cover plate 16 of the substrate 15 is contained via mould pressing process or etching technics shape
Into channel structure, the substrate 15 also containing be connected with the channel structure and pierce the substrate via mould pressing process, etch
Technique or the window structure of simple drilling technology formation, substrate 15 bonded to each other being installed together and the common structure of cover plate 16
Built up the micro-fluidic chip containing pipeline configuration and the liquid pool structure being attached thereto, the liquid pool be liquid pool 1, liquid pool 2,
Liquid pool 10, the locations of structures of the pipeline is located at the substrate 15 and the cover plate 16 interface zone bonded to each other, the window one
Side is blocked by the cover plate 16 and opposite side is opened, and the locations of structures of the window is exactly the liquid pool 1, liquid pool 2, liquid pool 10
Locations of structures, the quantity of the liquid pool is three, and two liquid pools therein are that liquid pool 1 and its locations of structures of liquid pool 2 are micro- positioned at this
The sample introduction end 19 of fluidic chip, a remaining liquid pool is that its locations of structures of liquid pool 10 is surveyed positioned at the actual sample introduction of the micro-fluidic chip
The terminal 20 that liquid flows in its chip during examination, the terminal 20 is located remotely from each other with the sample introduction end 19, one end of the pipeline via
Be similarly positioned in the manifold shape turnout 3 of the interface zone bonded to each other respectively with positioned at the liquid pool 1 at sample introduction end 19 and the liquid pool
2 UNICOMs, the other end of the pipeline and a remaining liquid pool for the terminal 20 positioned at the micro-fluidic chip are liquid pool 10
UNICOM, and, the working electrode that is sequentially respectively installed in the pipeline on diverse location and to electrode 8 and reference electrode 9,
The working electrode is by conductive electrode and the gold size for having embedded AIDS specific antibody being attached on the conductive electrode
Sensitive membrane is constituted, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is made up of four lateral parallel connections,
The quantity of the working electrode is four, and the installation position of four working electrodes is located in four laterals respectively, should
Four working electrodes are working electrode 5, working electrode 6, working electrode 12, working electrode 13 respectively, and, four works
It is the four kinds of Chinese mugworts that can be specifically bound to AIDS antigen respectively to make the specific antibody in the sensitive membrane structure of its top layer gold size of electrode
Sick antibody materials are grown, four kinds of antibody materials are that aids antibody p24 and aids antibody gp41 and AIDS are anti-respectively
Body gp120 and aids antibody gp36, for specifically deploying, 5 be its top layer gold size being installed in lateral 4
The working electrode that specific antibody material in sensitive membrane structure is AIDS specific antibody p24,6 be to be installed in lateral
The working electrode that the specific antibody material in the sensitive membrane structure of its top layer gold size in 7 is AIDS specific antibody gp41,
12 be that specific antibody material in the sensitive membrane structure of its top layer gold size being installed in lateral 11 resists for AIDS disease-specific
Body gp120 working electrode, 13 be that specificity in the sensitive membrane structure of its top layer gold size being installed in lateral 14 resists
Body material be AIDS specific antibody gp36 working electrode, the working electrode 5, working electrode 6, working electrode 12,
Its material of working electrode 13 is gold material or thermal decomposition conducting polymer material, the working electrode 5, working electrode 6, work
Make electrode 12, working electrode 13 its pattern and sheet or thread is presented, emphasis is, its material of the substrate 15 is poly dimethyl silicon
Oxygen alkane material, its surface of substrate 15 is the surface of primary form, the surface of the primary form its be intended to refer to not pass through
The surface of the primary form of any surface chemical modification or the material of any surface chemical modification, the structure of the micro fluidic device is also
Including miniature ultrasonic transducer units 18, and, higher-order of oscillation electric signal transmission cable 17, higher-order of oscillation electric signal transmission electricity
One end of cable 17 is linked together with the miniature ultrasonic transducer units 18, and the miniature ultrasonic transducer units 18 are installed in attaching
The position of the cover plate 16 of the micro-fluidic chip or the neighbouring terminal 20 of substrate 15；The miniature ultrasonic transducer units 18 its
Major function is that in the test of micro-fluidic chip actual sample introduction, the ultrasonic wave launched using it reduces sample solution and the pipe
Interfacial tension between the inwall in road, can be compatible, also, using the sample introduction end 19 and the terminal 20 with
Difference in the distance between the installation position of miniature ultrasonic transducer units 18 difference and its ultrasonic intensity experienced,
Difference between its interfacial tension of sample introduction end 19 described in induced synthesis and the terminal 20 its interfacial tension, the micro-fluidic chip
The two ends are that the interfacial tension difference between sample introduction end 19 and terminal 20 can be at the two ends of the micro-fluidic chip i.e. sample introduction end 19
Pressure gap is formed between terminal 20, the pressure gap can drive sample solution to be flowed to the direction of terminal 20；This is micro-
Type ultrasonic transducer 18 its function also include with its ultrasonic wave launched check large biological molecule contained in sample its
Absorption on the inner surface of pipeline, so check its body phase of the substrate 15 of the dimethyl silicone polymer material to the biology greatly point
The effect of swallowing up of son；Its function of the substrate 15 of the dimethyl silicone polymer material includes and cover plate 16 and working electrode 5, work
Make electrode 6, working electrode 12, working electrode 13 and the micro-fluidic chip is together built to electrode 8 and reference electrode 9, it is soft
The substrate of the dimethyl silicone polymer material its function that is soft and having elasticity is also included with its property to the strong absorption of ultrasonic wave, right
Ultrasonic wave is absorbed strongly, and thereby real within micro-fluidic chip terminal to the limited short distance between the sample introduction end
The rapid decrement of existing ultrasonic intensity；And, ultrasonic wave damper, its profile of ultrasonic wave damper is in block, tabular or rod
Shape；Its material of the ultrasonic wave damper is microcellular rubber, sponge rubber or microporous polyurethane elastomer；And, elastic clip should
Elastic force accompanies two clamping limbs, and the medial surface of each clamping limb is relative with the medial surface of another clamping limb, one of clamping limb
Medial surface be close to the sample introduction end 19 of the micro-fluidic chip, the medial surface of another clamping limb is close to the ultrasonic wave damper,
The elastic clip with its gripping strength by the sample introduction end 19 of the micro-fluidic chip and the ultrasonic wave damper it is bonded to each other be clipped in one
Rise, the strong consumption to ultrasonic energy that the ultrasonic wave damper is brought with its material, further support in the miniflow
Control chip terminal 20 to the rapid decrement that ultrasonic intensity is realized within the limited short distance between the sample introduction end 19, and
Thereby further expand the difference between described its interfacial tension of sample introduction end 19 and the terminal 20 its interfacial tension.In legend
It is depicted without also being depicted without the elastic clip in the ultrasonic wave damper, legend.
Arrow in legend indicate the micro-fluidic chip its in actual motion, by pressure at two ends difference drive, its test liquid
The flow direction of stream.
Miniature ultrasonic transducer units 18 and higher-order of oscillation electric signal transmission cable 17 are depicted without in Fig. 1；Also, Fig. 1
And the associate members such as the higher-order of oscillation electric signal generator and multiple tracks electrochemical workstation are depicted without in Fig. 2.
Involved miniature ultrasonic transducer units 18 are commercially available；It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal transmission cable 17 is commercially available；It can also be customized to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；It can also be customized to relevant manufacturers.
Each working electrode in this example structure and electrode and reference electrode via each special cable or can be said respectively
Get lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as annex or saying interface connection of getting lines crossed.
Capillary on usual expression and significance refers to hydrophilic capillary glass tube；Capillary channel involved by this case is hydrophobic
Capillary form pipeline.
Claims (10)
1. the special cheap AIDS diagnosis micro fluidic device of fluid type of drive, the structure of the micro fluidic device includes leading to more
Road micro-fluidic chip, the structure of the micro-fluidic chip includes the substrate and cover plate of installing bonded to each other together, the substrate and lid
Piece is plate object or tablet, and what is formed via mould pressing process or etching technics contained in that face towards the cover plate of the substrate
Channel structure, the substrate also containing be connected with the channel structure and pierce the substrate via mould pressing process, etching technics or letter
The window structure of single drilling technology formation, substrate bonded to each other being installed together has been built into jointly with the cover plate contains pipeline
The micro-fluidic chip of structure and the liquid pool structure being attached thereto, the locations of structures of the pipeline is mutually pasted positioned at the substrate with the cover plate
The interface zone of conjunction, its side of the window is blocked by the cover plate and opposite side is opened, and the locations of structures of the window is exactly the liquid pool
Locations of structures, the quantity of the liquid pool is three, and two liquid pools therein its locations of structures is located at the sample introduction of the micro-fluidic chip
End, its locations of structures of a remaining liquid pool is located at the end of liquid flowing in its chip when the actual sample introduction of the micro-fluidic chip is tested
End, the terminal is located remotely from each other with the sample introduction end, and one end of the pipeline is via the manifold for being similarly positioned in the interface zone bonded to each other
Shape 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 right
Electrode and reference electrode, the working electrode is by conductive electrode and is attached on the conductive electrode and has embedded AIDS
The gold size sensitive membrane of specific antibody is constituted, and the construction of the pipeline is in parallel construction, and the pipeline in parallel construction is by four points
Branch pipe(tube) parallel connection is constituted, and the quantity of the working electrode is four, and the installation position of four working electrodes is located at described four respectively
In bar lateral, and, the specific antibody in the sensitive membrane structure of its top layer gold size of four working electrodes is to AIDS respectively
Four kinds of aids antibody materials that sick antigen can be specifically bound, four kinds of antibody materials are aids antibody p24 and Chinese mugwort respectively
Disease antibody gp41 and aids antibody gp120 and aids antibody gp36 is grown, 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, it is characterised in that the substrate
Its material is dimethyl silicone polymer material, and its surface of the substrate is the surface of primary form, its meaning of the surface of the primary form
Refer to not by any surface chemical modification or the surface of the primary form of the material of any surface chemical modification, the miniflow
Controlling the structure of device also includes miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, the higher-order of oscillation telecommunication
One end of number transmission cable links together with the miniature ultrasonic transducer units, and the miniature ultrasonic transducer units are installed in this with attaching
The position of the cover plate of micro-fluidic chip or the neighbouring terminal of substrate；Its major function of the miniature ultrasonic transducer units is in miniflow
When controlling the actual sample introduction of chip and testing, the ultrasonic wave launched using it reduces the boundary between sample solution and the inwall of the pipeline
Face tension force, can be compatible, also, installs position with the miniature ultrasonic transducer units using the sample introduction end and the terminal
The distance between put the difference on difference and its ultrasonic intensity experienced, its interfacial tension of sample introduction end described in induced synthesis
With the difference between the terminal its interfacial tension, the interfacial tension difference between the micro-fluidic chip two ends can be micro-fluidic at this
Pressure gap is formed between the two ends of chip, the pressure gap can drive sample solution to the end flow；The miniature ultrasonic
Wave transducer its function also include with its ultrasonic wave launched check large biological molecule contained in sample its in the pipeline
Absorption on inner surface, and then check swallow up work of its body phase of the substrate of the dimethyl silicone polymer material to the large biological molecule
With；The substrate of the dimethyl silicone polymer material its function include with cover plate and working electrode and to electrode and reference electrode together
Build the micro-fluidic chip, it is soft and have the substrate of the dimethyl silicone polymer material of elasticity its function and also include with it to ultrasound
The property that ripple absorbs strongly, is absorbed strongly to ultrasonic wave, and thereby in the micro-fluidic chip terminal between the sample introduction end
Limited short distance within realize the rapid decrement of ultrasonic intensity；And, ultrasonic wave damper, the ultrasonic wave damper its
Profile is in block, tabular or bar-shaped；Its material of the ultrasonic wave damper is microcellular rubber, sponge rubber or microporous polyurethane elasticity
Body；And, elastic clip, the elastic force accompanies two clamping limbs, the medial surface of each clamping limb and the medial surface of another clamping limb
Relatively, the medial surface of one of clamping limb is close to the sample introduction end of the micro-fluidic chip, and the medial surface of another clamping limb is close to
The ultrasonic wave damper, the elastic clip is mutual by the sample introduction end of the micro-fluidic chip and the ultrasonic wave damper with its gripping strength
Snugly clip together, the strong consumption to ultrasonic energy that the ultrasonic wave damper is brought with its material, further
The fast express delivery of ultrasonic intensity is realized in support within micro-fluidic chip terminal to the limited short distance between the sample introduction end
Subtract, and thereby further expand the difference between described its interfacial tension of sample introduction end and the terminal its interfacial tension.
2. the special cheap AIDS diagnosis micro fluidic device of fluid type of drive according to claim 1, its feature
It is, the pipeline and the lateral and the manifold shape turnout are capillary channel.
3. the special cheap AIDS diagnosis micro fluidic device of fluid type of drive according to claim 1, its feature
Be, the thermal decomposition conducting polymer be by polyimides or polyacrylonitrile be heat-treated through anoxybiotic after the conductive material that is formed.
4. the special cheap AIDS diagnosis micro fluidic device of fluid type of drive according to claim 1, its feature
Be, 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. the special cheap AIDS diagnosis micro fluidic device of fluid type of drive according to claim 1, its feature
It is, the thickness of the gold size sensitive membrane is between 10 nanometers and 200 nanometers.
6. the special cheap AIDS diagnosis micro fluidic device of fluid type of drive according to claim 1, its feature
It is, its material of the cover plate in structure is dimethyl silicone polymer material.
7. the special cheap AIDS diagnosis micro fluidic device of fluid type of drive according to claim 1, its feature
Be, 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
Air line distance between one liquid pool is between 3 centimetres and 7 centimetres；The cover plate in structure and substrate its thickness between
Between 1.0 millimeters and 5.0 millimeters.
8. the special cheap AIDS diagnosis micro fluidic device of fluid type of drive according to claim 1, its feature
It is, the microcellular rubber is micropore silicon rubber or micropore fluorubber.
9. the special cheap AIDS diagnosis micro fluidic device of fluid type of drive according to claim 1, its feature
Be, the structure of the micro fluidic device also includes higher-order of oscillation electric signal generator, the higher-order of oscillation electric signal transmission cable its
The other end is connected with the higher-order of oscillation electric signal generator.
10. the special cheap AIDS diagnosis micro fluidic device of fluid type of drive according to claim 1, its feature
It is, its specified ultrasonic wave transmission power of the miniature ultrasonic transducer units is between 2 milliwatts and 2000 milliwatts, and 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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| CN201610065953.5A CN106990241A (en) | 2016-01-20 | 2016-01-20 | The special cheap AIDS diagnosis micro fluidic device of fluid type of drive |
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| CN201610065953.5A CN106990241A (en) | 2016-01-20 | 2016-01-20 | The special cheap AIDS diagnosis micro fluidic device of fluid type of drive |
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