CN106290858A - A kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate - Google Patents
A kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate Download PDFInfo
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- CN106290858A CN106290858A CN201510341977.4A CN201510341977A CN106290858A CN 106290858 A CN106290858 A CN 106290858A CN 201510341977 A CN201510341977 A CN 201510341977A CN 106290858 A CN106290858 A CN 106290858A
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- 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
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- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- 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
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
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Abstract
The present invention relates to a kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate, belong to analysis field tests.With the polydimethylsiloxane i.e. PDMS that inexpensively and easily processes to make the substrate of AIDS diagnosis micro-fluidic chip, there is some technology barriers；This case is for described obstacle.This case is characterized by, the PDMS with ecosystem surface selected by substrate, and the hinge-type fixture being attached to miniature ultrasonic transducer units manually fastened sample its neighbor positions of liquid stream terminal being positioned at this micro-fluidic chip, interfacial tension is reduced with ultrasound wave, utilize the PDMS strong absorbability to ultrasound wave simultaneously, reach ultrasonic intensity rapid decrement in short distance, thus interfacial tension difference is formed at the two ends of this chip, this difference provides a kind of and drives the strength that sample liquid stream flows to this terminal direction along hydrophobic capillary channel, this strength and simultaneously intercoupling with its mechanicalness of Micropump pumping strength of comprising in structure, Collaboration.
Description
Technical field
The present invention relates to a kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate, belong to analysis test neck
Territory.
Background technology
Associated multi-channel micro-fluidic AIDS diagnosis technical background, may refer to the patent of invention Shens such as CN 200910151219.0
Please case.
Only for itself overall general picture of microflow control technique, 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 ", this monograph is published by Science Press, and this monograph is for microflow control technique
Past, now, and, vision of the future etc. aspect, suffer from detailed, to be deep into detail long discussion.
So, the Important Problems that this case to be had a talk is paid close attention to.
The basic framework of micro-fluidic chip, including the substrate being etched with small fluid course and the cover plate fit together therewith,
Small fluid course on described substrate, before fit on cover plate, apparent on see to be exactly some micro-channel, wait until thereon
After covering cover plate, just real Guan Bi forms described small fluid course, and the conduit inner surface of this 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 completes 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 this micro-channel
The state on surface or character substantially determine integrality or the character of this small fluid course；Therefore saying, this builds at base
Inner surface state or the inner surface character of the micro-channel on sheet are key factors；In principle, any can keep or substantially protect
Hold the material of its solid forms, can be used to make substrate and cover plate, such as, it is possible to the material as substrate and cover plate is permissible
It is monocrystalline silicon piece, piezoid, sheet glass, high polymer such as polydimethylsiloxane, polymethyl methacrylate, Merlon etc.
Deng；Certainly, the selection of substrate can be identical with the selection of cover plate, it is also possible to differs；From material consumption, manufacture difficulty and
From the point of view of application popularization prospect etc. aspect, there is the selection of the least difference, especially that substrate between these materials, impact is relatively
Greatly.
In various substrates make material, polydimethylsiloxane, i.e. PDMS, the easiest molding, so
Substrate on to make micro-channel extremely simple, and this lower cost for material, make substrate with this polydimethyl siloxane material,
Suppress or etch micro-channel thereon, and the cover plate made with glass or the cheap material such as polypropylene or other plastic sheet matches,
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, promote.
But, thing is really not so simply.
One, this polydimethyl siloxane material, the material that i.e. abbreviation letter PDMS is referred to, itself is a kind of strong
Hydrophobic material, builds micro-channel on this material, if not carrying out the modified operation for this micro-channel surface, then,
After entirety has been assembled, after i.e. covering cover plate, lead to because its inner surface of described micro-channel in structure occupies most liquid stream
The inner surface in road, then, this its strong hydrophobic property of PDMS micro-channel inner surface, is deciding factor, and it can make class
Be similar to aqueous solution the fine liquid stream of polar liquid by becoming the most difficult, its flow resistance is big, and the most general Micropump is all
It is difficult to promote, certainly, if cover plate also selects to use this PDMS material, then, problem is substantially identical, similar；
Therefore, among prior art, it is modified modifying particular for the micro-channel inner surface on this PDMS material, is necessary
Operation；So, this operates pretty troublesome for the modification of PDMS micro-channel inner surface？That is not this problem, structure
Become serious technical puzzlement, be another problem: the PDMS polymer molecule tool that this its body of PDMS material substrate is internal mutually
Having the characteristic automatically diffusing to the surface, migrating, this substrate body internal PDMS polymer molecule mutually automatically diffuses to the surface, moves
The characteristic moved, can not maintain foot by making the state after the modification of that its inner surface of micro-channel of surface modification modification
The enough long time, holding time of its inner surface state of the micro-channel after that is surface-modified has substantially been only sufficient in laboratory
The time of portion's test experiments needs；In other words, through this PDMS micro-channel inner surface that surface modification or surface are modified, its
After modification or say the apparent condition formed after modification can not be lasting, but automatically tend to soon or say become surface again and change
Apparent condition before property, returns to the most hydrophobic apparent condition of that script in relatively short period of time, then, just think,
Such micro-fluidic chip can make in a large number, mass storage, be widely popularized, and answer is clearly, that is, it is impossible to.
Micro-channel on this PDMS material, if not doing surface modification, the fine liquid stream of polar solvent being similar to aqueous solution cannot pump
Sending and pass through, chip the most just cannot use；And if done surface modification, the state after cannot persistently keeping again it to modify, also
It is equally cannot popularization and application.
So, how to accomplish to utilize cheap PDMS material to make substrate, and table in described micro-channel can be released
Face decorating state cannot persistently, chip cannot make in a large number, lay in a large number and then be widely popularized and such a make this area numerous specially
The puzzlement that industry personnel are entangled with for a long time, it is simply that the highly difficult problem that its obvious technology barrier can not be despised.
Having there are a lot of days in this highly difficult problem, up to now, is not yet properly settled.
Its two, the PDMS material of non-surface modification, above it is stated that, its surface is the most hydrophobic, this most hydrophobic
Material surface and also another problem, that is, biomacromolecule can be adsorbed in the most hydrophobic this PDMS surface, and
And, the depression that these adsorbed biomacromolecules also can be further on PDMS surface further, gradually falls into gradually deep, directly
To the heavy body phase being trapped in PDMS substrate, in fact, this process, partly it is also due to PDMS material body internal mutually
Polymer molecule have diffuse to the surface, travel motion is caused；This situation, it is also possible to explain from another angle, i.e.
Internal to its diffusion into the surface, those polymer molecules of migration, the result of its motion mutually by PDMS body continuously, be by
Within those gradually have been involved in the body phase of PDMS substrate by the biomacromolecule of surface adsorption, briefly, these are inhaled
Attached biomacromolecule is swallowed up mutually by PDMS substrate body exactly；So, this PDMS substrate body swallows up biomacromolecule mutually
Phenomenon, its impact caused, necessarily cause the severe deviations relating to all kinds of test data of experiment of biomacromolecule.
As it has been described above, the problem of PDMS substrate is, its not only surface adsorption biomacromolecule, and swallow up biomacromolecule,
So, its disappearance of biomacromolecule as experiment test object will not stop because of the saturated absorption in surface, but, no
Disconnected adsorbed, the most constantly swallowed up.
About PDMS substrate in related experiment test process its body the most constantly swallow up test associated biomolecule macromole phenomenon, separately
A kind of explanation is to say, PDMS body mutually in there is substantial amounts of Minute pores, associated biomolecule macromole by after surface adsorption, depression
Enter these Minute pores, and then swallowed up；But, inventor thinks, those can allow that the air of miniature scale divides
Son clamp-ons described Minute pores therebetween, is not equal to them and also can directly allow that the biomacromolecule of relatively large yardstick enters, and two
Person's difference on yardstick is huge, must not make sweeping generalizations.Bypass explanation, in any case, analyze the biology of object as dependence test
Macromole is adsorbed by PDMS substrate micro-channel inner surface, and then is constantly swallowed up by PDMS substrate body phase, and this is known objective
The phenomenon existed.
In order to stop the effect of swallowing up relative to biomacromolecule of this PDMS substrate body, can be from containment PDMS surface to life
The absorption of thing macromole addresses, and way is aiming at this PDMS material surface and is chemically modified modification, for
From the point of view of PDMS is the situation of substrate material, it is simply that the surface of described micro-channel part is chemically modified modification, Jing Guohua
Learn the described micro-channel inner surface of modification, it is possible to contain its absorption to biomacromolecule, and then avoid biomacromolecule quilt
PDMS substrate body is swallowed up mutually；But, or that old problem, that is, the chemical modification on PDMS material surface changes
Apparent condition after property cannot persistently keep, the internal mutually polymer molecule of this PDMS substrate body its automatically diffuse to the surface,
The process migrated, can become that again script strong through the micro-channel inner surface state that surface chemical modification is modified soon and dredge
Water and the state of strong adsorption biomacromolecule, in other words, no matter how professionals in the field turn from side to side, this PDMS
Its micro-channel inner surface of substrate is the most rapidly to strong hydrophobic surface state evolution.
So, how can either obtain that PDMS material price is the cheapest, substrate makes extremely easy benefit, can reach again
Growth stage contains this PDMS substrate micro-channel inner surface absorption process to biomacromolecule, and then stops PDMS substrate body phase
The effect of swallowing up to biomacromolecule so that related chip manufactured goods are able to maintain that a shelf-life the most long, rational,
It it is exactly a difficult problem the most thorny.This difficult problem, as another difficult problem addressed above, makes the numerous specialty in this area equally
Personnel are entangled with for a long time, perplex, and this difficult problem is the highly difficult problem that its obvious technology barrier can not be despised equally.This difficulty
Having there are a lot of days in topic, up to now, is the most not yet properly settled.
Its three, as it has been described above, this PDMS micro-channel inner surface is the most hydrophobic, and surface chemical modification targetedly or come to the surface
Learning to modify is difficult to again persistently, therefore, actual can only still belong to the shortest in the apparent condition after its surface modification or surface are modified
It is used within phase；If have passed through that ofer short duration expiry date, and if using by force, due to surface shape
State, the most again near hydrophobic state, uses usual Micropump to drive sample liquid stream then to certainly exist bigger flow resistance,
So, just test liquid can only be forced to flow to target direction flowing by strengthening Micropump pump power and pumping pressure, as it has been described above,
This PDMS material is soft, pumps sample liquid stream with pumping pressure too high, machinery, and it enters will to cause this substrate
Sample end include sample introduction end near zone described micro-channel generation bubbling, expanded, distort, deform, and, this high-pressure situations
Under, it is in this sample introduction end and the micro-channel of near zone thereof and periphery is also susceptible to the stripping between substrate and cover plate, these feelings
Under shape, sample solution will enter the crack of the appearance between substrate and the cover plate formed after described stripping and flow over everywhere, and this is real
Border causes the damage of this micro-fluidic chip；Certainly, if this surface modification or surface are modified the most not in place, also result in
Within of short duration usual effect duration, said circumstances occurs；In the case of the additional Micropump of simple employing carries out liquid stream driving, above-mentioned
This problem exists all the time.If as it has been described above, entirely without doing the pre actions such as any described surface modification or surface modification,
So, this problem above-mentioned by even more serious, even without occur micro-channel bubbling described in sample introduction end and near zone thereof, expanded,
Distortion, the problem such as stripping between deformation and substrate and cover plate, merely because this flow resistance is excessive, use high pressure Micropump the most not
Sample liquid stream must be driven to march forward towards terminal side.
Summary of the invention
The technical problem to be solved is to provide a package solution, solves three addressed above simultaneously
The a series of difficult problem the most mutually involved together of aspect, and, this solution is applied to AIDS diagnosis with many
Channel microfluidic chip field, forms a kind of novel AIDS diagnosis Multichannel device.
The present invention solves described technical problem by following scheme, and the device that the program provides is a kind of Chinese mugwort relating to hydrophobic substrate
Growing disease diagnosis and use multichannel micro-fluidic chip device, the structure of this device includes multichannel micro-fluidic chip, this micro-fluidic chip
Structure includes bonded to each other being installed in substrate together and cover plate, and described substrate and cover plate are plate object or tablet, this substrate
That face towards this cover plate contain the channel structure formed via mould pressing process or etching technics, bonded to each other be installed together
This substrate and this cover plate be jointly built into the micro-fluidic chip containing pipeline configuration, the locations of structures of this pipeline is positioned at this substrate
The juncture area bonded to each other with this cover plate, the two ends of this pipeline are connected with sample introduction end and the terminal of this micro-fluidic chip respectively,
This sample introduction end is the injection end of this micro-fluidic chip sample solution, its chip when this terminal is the test of this micro-fluidic chip actual sample introduction
The terminal of interior sample solution flowing, this terminal is located remotely from each other with this sample introduction end, and the distance between this terminal and this sample introduction end is between 3
Centimetre and 10 centimetres between, in this pipeline, on diverse location, be sequentially equiped with working electrode and to electrode and reference electrode,
Described working electrode is by conductive electrode and the gold size having embedded acquired immune deficiency syndrome (AIDS) specific antigen that is attached on this conductive electrode
Sensitive membrane is constituted, and the structure of this pipeline is parallel construction, and the described pipeline in parallel construction is made up of four lateral parallel connections,
The quantity of described working electrode is four, and the installation position of these four working electrodes lays respectively in described four laterals, with
And, the specific antigen in its top layer gold size sensitive membrane structure of these four working electrodes is to tie aids antibody energy specificity respectively
The four kinds of acquired immune deficiency syndrome (AIDS) antigenic substances closed, these four kinds of antigenic substances are acquired immune deficiency syndrome (AIDS) specific antigen p24, gp41, gp120 respectively
And gp36, its material of described working electrode is gold material or thermal decomposition conducting polymer material, its pattern of described working electrode
Present lamellar or thread, it is important that, its material of this substrate is polydimethylsiloxane material, and its surface of this substrate is primary form
Surface, the surface of this primary form its be intended to refer to not through any surface chemical modification or any surface chemical modification
The surface of the primary form of this material, the structure of this device also includes hinge-type fixture, and this its appearance profile of hinge-type fixture is similar to
Hinge, this hinge-type fixture by two hinges being mutually hinged and run through one of these two hinges fastening screw and
One nut for manually fastening and hand break loose mated with this fastening screw and be connected together with this fastening turnbuckle is constituted,
This micro-fluidic chip is respectively mutually drawn close and clamp to two hinges of this hinge-type fixture with its tip, and described tip is positioned at this miniflow
In the locations of structures of the neighbouring described terminal of control chip, in a described hinge at least in, attaching is fixing is equiped with miniature surpassing
Acoustic wave transducer, and, higher-order of oscillation electric signal transmission cable, one end of this higher-order of oscillation electric signal transmission cable is miniature with this
Ultrasonic transducer links together；This hinge-type fixture provides a function facilitating this device to disassemble；This miniature ultrasonic
Its major function of transducer is when the actual sample introduction of micro-fluidic chip is tested, and utilizes its ultrasound wave launched to reduce sample solution
And the interfacial tension between the inwall of this its inner passage of micro-fluidic chip so that it is can be compatible, and, utilize described sample introduction end
And distance difference and its ultrasound wave experienced between described terminal and this miniature ultrasonic transducer units installation position is strong
Difference on degree, difference between its interfacial tension of sample introduction end and its interfacial tension of described terminal described in induced synthesis, this is micro-fluidic
Interfacial tension difference between these two ends of chip can form pressure gap, this pressure gap between these two ends of this micro-fluidic chip
Sample solution can be driven to described end flow；Its function of this miniature ultrasonic transducer units also includes holding back with its ultrasound wave launched
Only contained in sample its absorption on its inner passage inner surface of this micro-fluidic chip of biomacromolecule, and then it is poly-to check this
Its body of the substrate of dimethyl siloxane material is relative to the effect of swallowing up of this biomacromolecule；Softness also has this elastic poly dimethyl silicon
Its function of substrate of oxygen alkane material includes, with the character of its absorption strong to ultrasound wave, strongly absorbing ultrasound wave, and thereby
The rapid decrement of ultrasonic intensity is realized within limited short distance between this terminal of this micro-fluidic chip to this sample introduction end；With
And, Micropump, this Micropump is connected with this sample introduction end；The function of this Micropump is, at this sample solution and this micro-fluidic chip inside it
Under the precondition that interfacial tension between the inwall of passage is reduced by this ul-trasonic irradiation, the alternate compatibility increases, micro-with this
The mechanicalness pumping strength of pump carrys out its driving force brought of interfacial tension difference between the described two ends of this ultrasound wave induction
Amount is supported mutually, adjusts mutually, is mutually coupled, and pools one and drive test liquid to flow to described terminal in the way of Collaboration
The strength of direction flowing.
Described miniature ultrasonic transducer units can certainly be all installed in two described hinges；But, only installing one is micro-
Type ultrasonic transducer is the most enough dealt with and is employed.
Itself art-recognized meanings of hinge one word is known.
Itself art-recognized meanings of described Micropump one word is known for the professional in micro-fluidic chip field.
Piezoelectric pump, miniature peristaltic pump or the miniature air driven pump that described Micropump is the most miniature.
Described Micropump both can be with the Micropump being external form；This Micropump can also be to do into or say inside this micro-fluidic chip of embedding
The Micropump of the built in version of its sample introduction end structure position or this sample introduction end Near-neighbor Structure position.
Described gold size sensitive membrane is chitosan gold size solution and acquired immune deficiency syndrome (AIDS) specific antigen solution to be sufficiently mixed uniformly, uses point sample
Instrument point sample or coat specified structure position, and make its drying and forming-film form.Acquired immune deficiency syndrome (AIDS) specificity in described gold size sensitive membrane resists
The former acquired immune deficiency syndrome (AIDS) antigen being horseradish peroxidase or glucose oxidase labelling, described gold size sensitive membrane is included as fixing
Above-mentioned each acquired immune deficiency syndrome (AIDS) specific antigen and introduce complementary medium therein, described complementary medium such as chitosan, acetate fiber
Element, gelatin be therein a kind of or their mixture.
Described pipeline in described microfluidic chip structure includes described lateral, and its internal diameter size may each be arbitrarily selected
Size, but, for as far as possible less with liquid sample to be measured and the consideration that reduces the aspects such as reagent loss, described in described pipeline includes
Lateral the most all selects the passage of capillary level, the passage of described capillary level to imply that its internal diameter and the capillary on ordinary meaning
The passage that the internal diameter of pipe is suitable.The shape of cross section of described its inner passage of capillary tube can be arbitrary shape, described cross section
Shape is the most circular, oval, square, rectangle, bar shaped, naturally it is also possible to be arbitrary to there is the linear of bending, and,
The interior shape of described capillary tube is along with the extension of pipeline, and the shape of cross section of different parts can also allow to be different shapes.
Only for capillary tube one word, its art-recognized meanings is known.
Relate in structure is minute sized electrode to electrode and reference electrode, and its electrode shape may each be arbitrarily choosing
Fixed shape, described arbitrarily selected shape such as square piece shape, rectangular patch, strip or round sheet etc..Described to electricity
Itself the art-recognized meanings of vocabulary of pole and described reference electrode is known.
Only for itself the art-recognized meanings of the ultrasonic transducer one word professional for ultrasonic technology field, it is public
Know.
Various sizes, variously-shaped ultrasonic transducer are commercially available；Its size of commercially available miniature ultrasonic transducer units is permissible
Little to the magnitude only calculated with millimeter.
Only with regard to its technique for fixing on general industry application solid body surface of miniature ultrasonic transducer units itself and
Speech, for the professional in ultrasonic technology field, is known general technology.This is not launched superfluous words by this case.
Only itself micro-channel of naked PDMS substrate is molded or for lithographic technique, be open-and-shut known technology.
The industrial products market of involved higher-order of oscillation electric signal its all size of transmission cable is the most on sale.
The structure of this device can also include higher-order of oscillation electric signal generator；It is another for described higher-order of oscillation electric signal transmission cable
One end can be connected with this higher-order of oscillation electric signal generator.
Itself technology of involved higher-order of oscillation electric signal generator, for the professional in ultrasonic technology field, be
Simple and known；Described higher-order of oscillation electric signal generator can customize to ultrasonic instrument specialized factory.
The preferred scope of its specified ultrasonic emitting power of this miniature ultrasonic transducer units be between 5 milliwatts and 9000 milliwatts it
Between；The preferred scope of the frequency of its ultrasound wave operationally launched of this miniature ultrasonic transducer units be between 100KHz with
Between 12MHz.
This case device can further include some adnexaes certainly, described adnexa such as multiple tracks electrochemical workstation etc., institute
The art-recognized meanings stating multiple tracks electrochemical workstation is known.Each working electrode of relating in this case microfluidic chip structure and
To electrode and reference electrode etc., can be respectively via the most special the corresponding interface got lines crossed with described multiple tracks electrochemical workstation
Couple.Described special each the corresponding interface being used to each described electrode with described multiple tracks electrochemical workstation of getting lines crossed is carrying out phase
The private cable being mutually coupled with.Described micro-fluidic chip in this case device, its structure can also include micro-valve, the number of described micro-valve
Amount does not limits, according to actual needs, and any need position to be mounted that described micro-valve can be installed in this microfluidic chip structure；
This micro-valve one word is for the professional of micro fluidic chip technical field, and the art-recognized meanings of itself is known；This micro-valve
The manufacturing technology of itself and use technology are also known；This optional component of micro-valve.
The diameter of described working electrode can allow the suitable diameter being easily installed use being arbitrarily set, it is however recommended to
Or say preferred its scope of described diameter between 0.1 micron to 2000 micron；The length of described working electrode can permit
Permitted the length being easily installed use being arbitrarily set, it is however recommended to or to say preferred its scope of described length be at 1 micron
Between 15000 microns.
The described gold size being installed in described working electrode surface layer by spraying or point sample instrument point sample or the coating of other appropriate process is quick
Sense film, its thicknesses of layers can allow the thickness that the sample measuring liquid the treated generation electrical signals being arbitrarily set responds, but, push away
The thickness recommended the most preferably thickness is between 10 nanometers and 200 nanometers.
Described cover plate in chip structure, its material can allow to be any electrical insulating property material, such as: polypropylene, glass
Glass, polymethyl methacrylate, polydimethylsiloxane, etc., in order to make smaller size of micro-fluidic chip, such as do
Become the micro-fluidic chip of the super-small of length only 2.0 centimetres to 3.0 centimetres, and realize ultrasound wave in the distance that this is extremely short
Extremely fast decay, it may be preferred to polydimethylsiloxane is used as cover plate.Certainly, large-sized micro-fluidic chip selects
Use polydimethylsiloxane to be used as described cover plate, be also that this case technical scheme is allowed.
Described cover plate and its thickness of substrate can allow the thickness being easy to assembling being arbitrarily set, it is recommended that thickness or say preferably
Thickness be between 1.0 millimeters and 5.0 millimeters.Less thickness is conducive to saving material.
The using method of this case micro-fluidic chip:
This case drives liquid stream to flow in the capillary channel of this four-way micro-fluidic chip with described Dual Drive coupling operating mode,
Four-way electrochemical analytical instrument is utilized respectively four kinds of aids antibodies to be detected.
Detect corresponding four kinds of aids antibodies with four kinds of acquired immune deficiency syndrome (AIDS) antigens, detect corresponding four with four kinds of aids antibodies
Kind acquired immune deficiency syndrome (AIDS) antigen, similarly, can diagnosis of aids；The principle of its foundation is, necessarily resists in acquired immune deficiency syndrome (AIDS) patient
Former, antibody is also deposited, and mutually Reversible binding, forms reversible conjugate, therefore, detects antibody with antigen and thereby diagnose
Acquired immune deficiency syndrome (AIDS), goes to detect antigen diagnosis of aids with antibody, can reach diagnostic purpose.Certainly, its phase of different means
The electrode sensitive decorative layer answered technically and differs.
The concrete detection of this case micro-fluidic chip uses step as follows:
1, in micro-pipeline, blood serum sample liquid is added, under described Dual Drive coupling operating mode drives, various aids antibodies
Molecule is by the acquired immune deficiency syndrome (AIDS) specificity of the corresponding horseradish peroxidase-labeled of gold size sensitive membrane embedding on electrode surface in each passage
Antigen capture.
2, the acquired immune deficiency syndrome (AIDS) specific antigen of horseradish peroxidase-labeled and the aids antibody in blood serum sample are formed immune compound
Thing.
3, use multi-channel electrochemical analyzer, add the electron mediators such as catechol, use the above-mentioned reaction of amperometric detection
The curent change caused, is derived from kind and the content of various analyte.
4, result is comprehensively analyzed, aids antibody is carried out comprehensive diagnos.
It is an advantage of the invention that its close position of described terminal at described micro-fluidic chip positions described hinge-type fixture, with
Attached the miniature ultrasonic transducer units installed in this its hinge of hinge-type fixture, utilized its low-power launched, high-frequency band
Ultrasound wave so that without surface chemical modification or surface chemical modification this most hydrophobic micro-fluidic chip internal pipeline its
The compatibility between tube wall and test object water solution is significantly increased, and what this was sample liquid stream is possible by providing a reality
Property；Meanwhile, its strong absorbability to ultrasound wave of polydimethylsiloxane substrate is utilized, in comparatively short distance, the most just
It is, in the shortest distance of the only several centimeters yardstick from described terminal to described sample introduction end, to reach the quick of ultrasonic intensity
Successively decreasing, thereby the difference of described interfacial tension is caused at the described two ends at this micro-fluidic chip, the interfacial tension between these two ends
Difference can cause a kind of driving force, and its function of driving force that this kind causes because of interfacial tension difference is to drive sample liquid stream to exist
Flow to described terminal direction in the most hydrophobic capillary channel；And simultaneous described Micropump in structure, its function
It is that the interfacial tension between the inwall of this sample solution and this its inner passage of micro-fluidic chip is dropped by this ul-trasonic irradiation
Under the precondition that the compatibility low, alternate increases, pump strength with the mechanicalness of this Micropump and come and described the two of the induction of this ultrasound wave
Its driving force brought of interfacial tension difference between end is supported mutually, adjusts mutually, is mutually coupled, with Collaboration
Mode pools one and drives test liquid to flow to the strength of described terminal direction flowing；The existence of this Micropump so that this miniature ultrasonic
Its ultrasonic emitting intensity of wave transducer can be allowed to appropriateness reduction, and this is for containing ultrasound wave sensitive composition in detection object
Situation is particularly suitable for；And due to this ultrasonic transducer and the existence of radiated ultrasound wave thereof, it is possible to increase the alternate compatibility, fall
Low interfacial tension, and provide this two ends interfacial tension difference its special driving force brought, then, in this case,
Its flow resistance in this micro-channel of sample liquid stream is greatly reduced, and correspondingly, its running resistance of this Micropump is greatly reduced, so,
This Micropump just can be to carry out the pumping work for described sample solution than relatively low pumping pressure, due to mechanical pumping
Pressure is greatly reduced, and therefore, in such a situation, is just not susceptible to cause because sample introduction terminal tool pumping pressure is excessive
Described sample introduction end and the described micro-channel bubbling of near zone thereof, expand, deform, distort and between this region substrate and cover plate
Stripping etc. problem；This Dual Drive of this case couples the scheme of running and adds the manipulation for this sample fluid flow action
Property, it is possible to allow to use ultrasonic intensity, ultrasonic frequency, Micropump pump power, Micropump pumping pressure etc. multiple indexs
Flow rate, flowing action for this flowing include that flow forward or time-out flowing or acceleration flowing etc. flowing action carry out many
Parameter accurately manipulates；By the scheme of this Dual Drive of this case coupling running, entirely without must be to the base of this polydimethylsiloxane material
Its micro-channel of sheet etc. relevant surfaces carries out any surface chemical modification or surface chemical modification, has altogether dispensed with this surface chemistry
Modify or the laborious procedures of surface chemical modification；On the other hand, the ultrasound wave of this low-power, high-frequency band, additionally it is possible to containment examination
The absorption on this literalness naked its inner surface of pipeline of polydimethylsiloxane substrate of the biomacromolecule in sample, and then containment
The effect of swallowing up of this polydimethylsiloxane substrate the most described biomacromolecule of its body；Described antigen, antibody and antigen are with anti-
The Reversible binding thing of body is the most all belonging to the type of described biomacromolecule；Due to described adsorption and described gulping down
No effect is not contained effectively, and therefore, dependence test result will be better able to reflect practical situation objectively；This low-power, height
Again and again the effect of section ultrasound wave, the most also includes facilitating what the Reversible binding between antigen, antibody reacted quickly to reach, and this makes
Dependence test operation can be to complete than speed faster.
As it has been described above, the existence of this Micropump so that its ultrasonic emitting intensity of this miniature ultrasonic transducer units can be allowed to fit
Degree reduces, then, this feature contributes to protecting its sensitive coating of described working electrode, is allowed to from ultrasound injury.
Based on this case scheme, completely without carrying out repairing for the surface chemistry of this polydimethylsiloxane its relevant surfaces of substrate
Decorations or surface chemical modification operation, therefore, this surface chemical modification layer or surface chemical modification layer not need to exist,
So, its body phase interior polymeric thing molecule of this polydimethylsiloxane substrate the most automatically diffuses to the surface, migrates what it was caused
The damaging influence of described surface chemical modification layer or surface chemical modification layer is not existed.
The technical scheme of this case has dissolved relevant to its application of polydimethylsiloxane substrate addressed above totally
Row technical barrier.Based on this case scheme, this kind the most inexpensively and easily polydimethyl siloxane material of processing and fabricating just has can
Can at this micro-fluidic chip, it be prepared, produces, application etc. field plays bigger effect.
Fixing in this its hinge of hinge-type fixture in this case structure and installed described miniature ultrasonic transducer units, this structure provides
One function facilitating this device to disassemble, so, this hinge-type fixture is together with miniature ultrasonic transducer units appended in its hinge
Just can be mutually disengaged with this micro-fluidic chip easily, then, the component that this part can freely depart from just can circulate benignly ground
Reuse many times；This architectural feature is conducive to saving the use cost of this device.
Accompanying drawing explanation
Fig. 1 is its rough outside side view of this micro flow control chip device of this case.
In figure, 1 is hinge-type fixture, and 2 indicate linkwork position, and 3 is fastening screw, and 4 is higher-order of oscillation telecommunication
Number transmission cable, 5 is miniature ultrasonic transducer units, and 6,11 is two hinges that locations of structures is different respectively, and 7 is cover plate, 8
Being substrate, 9 is sample introduction end, and 10 is terminal, and 12 is nut, and 13 is infusion tube, and 14 is Micropump；This conjunction in legend
Page clamp structure is only the legend structure of signal, and this its structure of hinge-type fixture actual is not limited to this legend hinge-type fixture knot
Structure；Arrow in legend indicate this micro-fluidic chip its when actual motion, driven by pressure at two ends difference, its sample liquid stream
Flow direction.
Detailed description of the invention
In this embodiment of this case that Fig. 1 is shown, the structure of this device includes multichannel micro-fluidic chip, this micro-fluidic core
The structure of sheet includes bonded to each other being installed in substrate 8 together and cover plate 7, and described substrate 8 and cover plate 7 are plate object or sheet
Shape thing, the channel structure formed via mould pressing process or etching technics, phase are contained in that face towards this cover plate 7 of this substrate 8
It is jointly mounted to this substrate 8 together mutually and is jointly built into the micro-fluidic chip containing pipeline configuration with this cover plate 7, this pipeline
Locations of structures be positioned at the juncture area that this substrate 8 is bonded to each other with this cover plate 7, the two ends of this pipeline respectively with this micro-fluidic core
Sample introduction end 9 and the terminal 10 of sheet connect, and this sample introduction end 9 is the injection end of this micro-fluidic chip sample solution, this terminal 10
The terminal that when being the test of this micro-fluidic chip actual sample introduction, in its chip, sample solution flows, this terminal 10 and this sample introduction end 9 phase
Mutually away from, the distance between this terminal 10 and this sample introduction end 9 between 3 centimetres and 10 centimetres, not coordination in this pipeline
Putting and be sequentially equiped with working electrode and to electrode and reference electrode, described working electrode is by conductive electrode and is attached to
The gold size sensitive membrane having embedded acquired immune deficiency syndrome (AIDS) specific antigen on this conductive electrode is constituted, and the structure of this pipeline is parallel construction,
The described pipeline in parallel construction is made up of four lateral parallel connections, and the quantity of described working electrode is four, these four work
The installation position of electrode lays respectively in described four laterals, and, its top layer gold size sensitive membrane knot of these four working electrodes
Specific antigen in structure is four kinds of acquired immune deficiency syndrome (AIDS) antigenic substances that can be specific binding to aids antibody respectively, these four kinds of antigen things
Matter is acquired immune deficiency syndrome (AIDS) specific antigen p24, gp41, gp120 and gp36 respectively, and its material of described working electrode is gold material
Or thermal decomposition conducting polymer material, its pattern of described working electrode presents lamellar or thread, it is important that, this its material of substrate 8
Being polydimethylsiloxane material, this its surface of substrate 8 is the surface of primary form, the surface of this primary form its be meant to
It is not through the surface of primary form of this material of any surface chemical modification or any surface chemical modification, the knot of this device
Structure also includes hinge-type fixture 1, and this its appearance profile of hinge-type fixture 1 likeness in form hinge, this hinge-type fixture 1 is by being hinged
Two hinges 6,11 together and run through the fastening screw 3 of these two hinges 6,11 and one and this fastening
Screw 3 mates and the nut 12 for manually fastening and hand break loose that connects together with this fastening screw 3 is constituted, this spiral shell
Cap 12 have employed the butterfly nut being easier manual operation in this example, and butterfly nut is commercially available, this hinge-type fixture 1
Two hinges 6,11 respectively mutually draw close and clamp this micro-fluidic chip with its tip, described tip is positioned at this micro-fluidic chip
Neighbouring described terminal 10 locations of structures on, a described hinge at least in attaches and fixing is equiped with miniature ultrasonic
Wave transducer, in this example, this miniature ultrasonic transducer units 5 is to attach to be fixed in hinge 6, and, higher-order of oscillation electric signal
Transmission cable 4, one end of this higher-order of oscillation electric signal transmission cable 4 links together with this miniature ultrasonic transducer units 5；Should
Hinge-type fixture 1 provides a function facilitating this device to disassemble；This its major function of miniature ultrasonic transducer units 5 is micro-
During the test of fluidic chip actual sample introduction, it is internal logical to reduce sample solution and this micro-fluidic chip to utilize its ultrasound wave launched
Interfacial tension between the inwall in road so that it is can be compatible, and, utilize described sample introduction end 9 and described terminal 10 and be somebody's turn to do
Distance difference between miniature ultrasonic transducer units 5 installation position and the difference on its ultrasonic intensity experienced, induction
Form the difference between described its interfacial tension of sample introduction end 9 and its interfacial tension of described terminal 10, these two ends of this micro-fluidic chip
9, the interfacial tension difference between 10 can form pressure gap, this pressure differential between these two ends 9,10 of this micro-fluidic chip
Different sample solution can be driven to flow to described terminal 10 direction；This its function of miniature ultrasonic transducer units 5 also includes being sent out with it
The ultrasound wave penetrated checks its absorption on its inner passage inner surface of this micro-fluidic chip of biomacromolecule contained in sample,
And then check its body of substrate 8 effect of swallowing up relative to this biomacromolecule of this polydimethylsiloxane material；Softness also has elasticity
Its function of substrate 8 of this polydimethylsiloxane material include, with the character of its absorption strong to ultrasound wave, ultrasound wave being carried out
Strong absorption, and thereby realize super within this terminal 10 of this micro-fluidic chip arrives the limited short distance between this sample introduction end 9
The rapid decrement of intensity of acoustic wave；And, Micropump 14, this Micropump 14 is connected with this sample introduction end 9；The function of this Micropump 14 is,
Interfacial tension between this sample solution with the inwall of this its inner passage of micro-fluidic chip is reduced by this ul-trasonic irradiation, phase
Between under the precondition that increases of the compatibility, pump strength with the mechanicalness of this Micropump 14 and come and the described two ends of this ultrasound wave induction
9, its driving force brought of interfacial tension difference between 10 is supported mutually, adjusts mutually, is mutually coupled, with collaborative fortune
The mode made pools one and drives test liquid to flow to the strength of described terminal 10 direction flowing.
Arrow in legend indicate this micro-fluidic chip its when actual motion, driven by two ends 9,10 pressure differential, its
The flow direction of sample liquid stream.
Fig. 1 is depicted without the associate members such as described higher-order of oscillation electric signal generator.
Described Micropump 14 can customize to specialized factory.
Described its main body of hinge-type fixture can utilize commercially available hinge simply to change a social system；Can also customize to five metals processing factory.
Involved miniature ultrasonic transducer units 5 is commercially available；Can also customize to ultrasonic transducer producer.
Involved higher-order of oscillation electric signal transmission cable 4 is commercially available；Can also be to ultrasonic transducer producer or cable special manufacturer
Family's customization.
Involved higher-order of oscillation electric signal generator market has the product close to needs commercially available；Can also customize to relevant manufacturers.
Involved its inner passage of this micro-fluidic chip of this case is the pipeline of hydrophobic capillary tube form.
Described Micropump both can be with the Micropump being external form；This Micropump can also be to do into or say inside this micro-fluidic chip of embedding
The Micropump of the built in version of its sample introduction end structure position or this sample introduction end Near-neighbor Structure position.Micropump in legend is external form
Micropump；This Micropump can certainly do into or say the embedding internal sample introduction end of this microfluidic chip structure or its Near-neighbor Structure position
The Micropump of described built in version, its basic structure key element is identical with the Micropump of external form.
Each working electrode in this example structure and can be respectively via the most special cable or say to electrode and reference electrode
Get lines crossed respectively with the corresponding cable interface of the multiple tracks electrochemical workstation as adnexa or say interface of getting lines crossed and couple.
This case device is to detect multiple corresponding aids antibody, thereby diagnosis of aids with multiple acquired immune deficiency syndrome (AIDS) antigen.
Claims (10)
1. relating to an AIDS diagnosis multichannel micro-fluidic chip device for hydrophobic substrate, the structure of this device includes multichannel
Micro-fluidic chip, the structure of this micro-fluidic chip includes bonded to each other being installed in substrate together and cover plate, described substrate and cover plate
Being plate object or tablet, the groove formed via mould pressing process or etching technics is contained in that face towards this cover plate of this substrate
Road structure, this substrate being installed together bonded to each other and this cover plate have been built into the micro-fluidic chip containing pipeline configuration jointly,
The locations of structures of this pipeline is positioned at the juncture area that this substrate is bonded to each other with this cover plate, and the two ends of this pipeline are micro-fluidic with this respectively
The sample introduction end of chip and terminal connect, and this sample introduction end is the injection end of this micro-fluidic chip sample solution, and this terminal is this miniflow
The terminal of sample solution flowing in its chip during control chip actual sample introduction test, this terminal is located remotely from each other with this sample introduction end, this terminal
And the distance between this sample introduction end is between 3 centimetres and 10 centimetres, in this pipeline, on diverse location, sequentially it is equiped with work
Electrode and to electrode and reference electrode, described working electrode is by conductive electrode and is attached to the bag on this conductive electrode
The gold size sensitive membrane having buried acquired immune deficiency syndrome (AIDS) specific antigen is constituted, and the structure of this pipeline is parallel construction, the described pipe in parallel construction
Road is made up of four lateral parallel connections, and the quantity of described working electrode is four, and the installation position of these four working electrodes is respectively
It is positioned at described four laterals, and, the specific antigen in its top layer gold size sensitive membrane structure of these four working electrodes divides
Not being the four kind acquired immune deficiency syndrome (AIDS) antigenic substances specific binding to aids antibody energy, these four kinds of antigenic substances are that acquired immune deficiency syndrome (AIDS) is special respectively
Property antigen p24, gp41, gp120 and gp36, its material of described working electrode be gold material or thermal decomposition conducting polymer
Material, its pattern of described working electrode presents lamellar or thread, it is characterised in that its material of this substrate is polydimethylsiloxane
Material, its surface of this substrate is the surface of primary form, the surface of this primary form its be intended to refer to not through any surface
The surface of the primary form of this material of chemical modification or any surface chemical modification, the structure of this device also includes that hinge-type presss from both sides
Tool, this its appearance profile of hinge-type fixture likeness in form hinge, this hinge-type fixture is by two hinges being mutually hinged and passes through
One that wears these two hinges fastens screw and the use mated and be connected together with this fastening turnbuckle with this fastening screw
Nut in manually fastening and hand break loose is constituted, and two hinges of this hinge-type fixture are respectively mutually drawn close with its tip and clamp this
Micro-fluidic chip, described tip is positioned in the locations of structures of neighbouring described terminal of this micro-fluidic chip, at least in
Attach in individual described hinge to fix and be equiped with miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, this high frequency
One end of vibration electric signal transmission cable links together with this miniature ultrasonic transducer units；This hinge-type fixture provides a side
Just the function that this device is disassembled；Its major function of this miniature ultrasonic transducer units is when the actual sample introduction of micro-fluidic chip is tested, profit
Reduce the interfacial tension between the inwall of sample solution and this its inner passage of micro-fluidic chip with its ultrasound wave launched, make
It can be compatible, and, utilize between described sample introduction end and described terminal and this miniature ultrasonic transducer units installation position away from
Deviation is different and difference on its ultrasonic intensity experienced, its interfacial tension of sample introduction end and described terminal described in induced synthesis
Difference between its interfacial tension, the interfacial tension difference between these two ends of this micro-fluidic chip can this micro-fluidic chip this two
Forming pressure gap between end, this pressure gap can drive sample solution to described end flow；This miniature ultrasonic transducer units its
Function also include with its ultrasound wave launched check in sample contained biomacromolecule its at this micro-fluidic chip inside it
Absorption on channel inner surface, and then check its body swallowing up relative to this biomacromolecule of substrate of this polydimethylsiloxane material
Effect；Soft and this polydimethylsiloxane material of having elasticity its function of substrate includes with the property of its absorption strong to ultrasound wave
Matter, absorbs strongly to ultrasound wave, and thereby limited short distance between this terminal of this micro-fluidic chip to this sample introduction end
Within realize the rapid decrement of ultrasonic intensity；And, Micropump, this Micropump is connected with this sample introduction end；The function of this Micropump is,
Interfacial tension between this sample solution with the inwall of this its inner passage of micro-fluidic chip is reduced by this ul-trasonic irradiation, phase
Between under the precondition that increases of the compatibility, pump strength with the mechanicalness of this Micropump and come between the described two ends of this ultrasound wave induction
Its driving force brought of interfacial tension difference support mutually, adjust mutually, be mutually coupled, converge in the way of Collaboration
Being polymerized to one drives test liquid to flow to the strength of described terminal direction flowing.
A kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate the most according to claim 1, its
Being characterised by, described pipeline includes that described lateral is capillary channel.
A kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate the most according to claim 1, its
Being characterised by, described thermal decomposition conducting polymer is the electric conductivity material formed after anoxybiotic heat treatment by polyimides or polyacrylonitrile
Material.
A kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate the most according to claim 1, its
Be characterised by, the width of described working electrode or diameter between 0.1 micron to 2000 micron, and, described work electricity
The length of pole is between 1 micron to 15000 micron.
A kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate the most according to claim 1, its
Being characterised by, the thickness of described gold size sensitive membrane is between 10 nanometers and 200 nanometers.
A kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate the most according to claim 1, its
Being characterised by, its material of described cover plate in structure is polydimethylsiloxane material.
A kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate the most according to claim 1, its
Being characterised by, described Micropump is miniature piezoelectric pump, miniature peristaltic pump or miniature air driven pump.
A kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate the most according to claim 1, its
Being characterised by, described cover plate in structure and its thickness of substrate are all between 1.0 millimeters and 5.0 millimeters.
A kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate the most according to claim 1, its
Being characterised by, the structure of this device also includes higher-order of oscillation electric signal generator, and it is another for described higher-order of oscillation electric signal transmission cable
One end is connected with this higher-order of oscillation electric signal generator.
A kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate the most according to claim 1, its
Being characterised by, its specified ultrasonic emitting power of this miniature ultrasonic transducer units is between 5 milliwatts and 9000 milliwatts, and this is micro-
The frequency of its ultrasound wave operationally launched of type ultrasonic transducer is between 100KHz and 12MHz.
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| CN201510341977.4A CN106290858A (en) | 2015-06-11 | 2015-06-11 | A kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate |
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| CN201510341977.4A CN106290858A (en) | 2015-06-11 | 2015-06-11 | A kind of AIDS diagnosis multichannel micro-fluidic chip device relating to hydrophobic substrate |
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Cited By (1)
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| CN106556708A (en) * | 2015-09-24 | 2017-04-05 | 宁波大学 | The micro flow control chip device containing hydrophobic substrate of two kinds of type of drive coupling runnings |
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