CN106140336A - Interphase interface characteristic is relied on to reach the micro flow control chip device of test liquid streaming - Google Patents

Abstract

The present invention relates to a kind of micro flow control chip device relying on interphase interface characteristic to reach test liquid streaming, belong to analysis field tests.Use the polydimethylsiloxane inexpensively and easily processed i.e. PDMS to make the substrate of micro-fluidic chip, some difficult problems of physical presence；Its surface of this PDMS material is the most hydrophobic, and surface modification or surface are modified targetedly, and its effect is difficult to persistently, and this case aims to solve the problem that this series relevant issues.This case is characterized by, the PDMS with ecosystem surface selected by substrate, and in sample its neighbor positions of liquid stream terminal fixing installing miniature ultrasonic transducer units of 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, and interfacial tension difference is thus formed at the two ends of this chip, this interfacial tension difference causes these two ends to form pressure differential, and this pressure differential drives sample liquid stream to flow along capillary channel to this terminal direction.

Description

Interphase interface characteristic is relied on to reach the micro flow control chip device of test liquid streaming

Technical field

The present invention relates to a kind of micro flow control chip device relying on interphase interface characteristic to reach test liquid streaming, belong to analysis test Field.

Background technology

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.

The field that micro-fluidic chip is often applied to includes the sample solution containing biomacromolecule is carried out various analysis, detection.

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 The apparent condition formed after modification or after day modification can not be lasting, but automatically tend to or become again day surface soon 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.

Summary of the invention

The technical problem to be solved is to provide a package solution, solves two addressed above simultaneously A difficult problem.

The present invention solves described technical problem by following scheme, and the device that the program provides is a kind of support interphase interface characteristic Reaching the micro flow control chip device of test liquid streaming, the structure of this device includes micro-fluidic chip, the structure of this micro-fluidic chip Being installed in substrate together and cover plate including bonded to each other, its test liquid of this micro-fluidic chip flows to sample end and this sample fluid flow Terminal be located remotely from each other, the distance between this sample introduction end and this terminal between 3 centimetres and 10 centimetres, it is important that, this base Its material of sheet is polydimethylsiloxane material, and its surface of this substrate is the surface of primary form, its meaning of the surface of this primary form Think to refer to not through the surface of primary form of this material of any surface chemical modification or any surface chemical modification, this dress The structure put also includes miniature ultrasonic transducer units, and, higher-order of oscillation electric signal transmission cable, this higher-order of oscillation electric signal passes One end of transmission cable links together with this miniature ultrasonic transducer units, and this miniature ultrasonic transducer units is installed in this miniflow with attaching The cover plate of control chip or the position of the neighbouring described terminal of substrate；Its major function of this miniature ultrasonic transducer units is at micro-fluidic core During the test of sheet actual sample introduction, utilize its ultrasound wave launched to reduce the interior of sample solution and this its inner passage of micro-fluidic chip Interfacial tension between wall so that it is can be compatible, and, utilize described sample introduction end and described terminal to change with this miniature ultrasonic Can the distance difference between device installation position and the difference on its ultrasonic intensity experienced, sample introduction end described in induced synthesis Difference between its interfacial tension and its interfacial tension of described terminal, the interfacial tension difference meeting between these two ends of this micro-fluidic chip Forming pressure gap between these two ends of this micro-fluidic chip, this pressure gap can drive sample solution to described end flow； Its function of this miniature ultrasonic transducer units also include with its ultrasound wave launched check in sample contained biomacromolecule its Absorption on its inner passage inner surface of this micro-fluidic chip, and then check its body phase of substrate of this polydimethylsiloxane material To the effect of swallowing up of this biomacromolecule；Soft and this polydimethylsiloxane material of having elasticity its function of substrate includes with it The character of absorption strong to ultrasound wave, absorbs strongly to ultrasound wave, and thereby in this terminal of this micro-fluidic chip to this sample introduction The rapid decrement of ultrasonic intensity is realized within limited short distance between end.

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；With Sample ground, the technology of hole-opening known simple technique especially on naked PDMS substrate.This is not launched superfluous words by this case.

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 2 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 can with micro-fluidic chip with the use of Electrically or optically detection equipment.Described electricity, optics etc. and micro-fluidic chip with the use of equipment, may refer to described Monograph.

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 day preferred Thickness be between 1.0 millimeters and 5.0 millimeters.Less thickness is conducive to saving material.

It is an advantage of the invention that its close position of described terminal at described micro-fluidic chip is installed miniature ultrasonic and changed with attaching Energy device, utilizes its low-power launched of this miniature ultrasonic transducer units, the ultrasound wave of high-frequency band so that without coming to the surface The compatibility learned between modified this most hydrophobic its tube wall of micro-fluidic chip internal pipeline and test object water solution significantly increases Add, this for sample liquid stream by providing a realistic possibility；Meanwhile, utilize polydimethylsiloxane substrate its to ultrasonic The strong absorbability of ripple, in comparatively short distance, it is, the only several centimeters from described terminal to described sample introduction end In the shortest distance of yardstick, reaching the rapid decrement of ultrasonic intensity, thereby institute is caused at the described two ends at this micro-fluidic chip State the difference of interfacial tension, and then, utilize the pressure between its these two ends formed of difference of the interfacial tension between these two ends Difference, flows to described terminal direction in driving the sample liquid stream capillary channel that script is the most hydrophobic in micro-fluidic chip.Mat By this case liquid stream drive scheme, entirely without the substrate of this polydimethylsiloxane material and internal pipeline thereof being carried out any table Face chemical modification or surface chemical modification, altogether dispensed with the laborious procedures of this surface chemical modification or surface chemical modification；And Altogether dispense with the equipment of traditional Micropump etc；On the other hand, the ultrasound wave of this low-power, high-frequency band, moreover it is possible to The enough absorption on this literalness naked its inner surface of pipeline of polydimethylsiloxane substrate of the biomacromolecule in containment sample, And then contain the effect of swallowing up of this polydimethylsiloxane substrate the most described biomacromolecule of its body；Due to described adsorption And described swallowing up acts on and effectively being contained, therefore, dependence test result will be better able to reflect practical situation objectively.

Change owing to being made without the surface chemical modification for this polydimethylsiloxane its relevant surfaces of substrate or surface chemistry Property operation, therefore, this surface chemical modification layer or surface chemical modification layer not need exist, then, this poly-diformazan Its body phase interior polymeric thing molecule of radical siloxane substrate diffuses to the surface the most automatically, migrate it caused to described surface chemistry The damaging influence of decorative layer or surface chemical modification layer does not exists.

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, the most cheap polydimethyl siloxane material of this kind is the most likely at this micro-fluidic chip Prepare, produce, application etc. field plays bigger effect.

Accompanying drawing explanation

Fig. 1 is its rough outside side view of this device of this case.

In figure, 1 is the substrate of polydimethylsiloxane material, and 2 is cover plate, and 3 is higher-order of oscillation electric signal transmission cable, 4 Being miniature ultrasonic transducer units, 5 is the described sample introduction end of this micro-fluidic chip, and 6 is the described terminal of this micro-fluidic chip；Figure Arrow in example indicate this micro-fluidic chip its when actual motion, driven by pressure at two ends difference, the flowing of its sample liquid stream Direction.

Detailed description of the invention

In this embodiment of this case that Fig. 1 is shown, the structure of this device includes micro-fluidic chip, the knot of this micro-fluidic chip Structure includes bonded to each other being installed in substrate 1 together and cover plate 2, and its test liquid of this micro-fluidic chip flows to sample end 5 and this sample The terminal 6 of fluid flow is located remotely from each other, the distance between this sample introduction end 5 and this terminal 6 between 3 centimetres and 10 centimetres, It is important that, this its material of substrate 1 is polydimethylsiloxane material, and this its surface of substrate 1 is the surface of primary form, and this is former The surface of raw form its be intended to refer to not through this material former of any surface chemical modification or any surface chemical modification The surface of raw form, the structure of this device also includes miniature ultrasonic transducer units 4, and, higher-order of oscillation electric signal transmission cable 3, one end of this higher-order of oscillation electric signal transmission cable 3 links together with this miniature ultrasonic transducer units 4, this miniature ultrasonic Wave transducer 4 is installed in the cover plate 2 of this micro-fluidic chip or the position of the neighbouring described terminal 6 of substrate 1 with attaching；This is micro- Its major function of type ultrasonic transducer 4 is when the actual sample introduction of micro-fluidic chip is tested, and utilizes its ultrasound wave launched to drop Interfacial tension between the inwall of low sample solution and this its inner passage of micro-fluidic chip so that it is can be compatible, and, utilize Distance difference between described sample introduction end 5 and described terminal 6 and this miniature ultrasonic transducer units 4 installation position and its felt The difference on ultrasonic intensity being subject to, its interfacial tension of sample introduction end 5 described in induced synthesis and described its interfacial tension of terminal 6 it Between difference, the interfacial tension difference between these two ends 5,6 of this micro-fluidic chip can be at these two ends 5,6 of this micro-fluidic chip Between formed pressure gap, this pressure gap can drive sample solution to flow to described terminal 6 direction；This miniature ultrasonic transducing Its function of device 4 also include with its ultrasound wave launched check in sample contained biomacromolecule its at this micro-fluidic chip Absorption on its inner passage inner surface, and then big relative to this biology point of its body of substrate 1 checking this polydimethylsiloxane material The effect of swallowing up of son；Soft and this polydimethylsiloxane material of having elasticity its function of substrate 1 includes with it strong to ultrasound wave The character of strong absorption, absorbs strongly to ultrasound wave, and thereby between this terminal 6 of this micro-fluidic chip to this sample introduction end 5 Limited short distance within realize the rapid decrement of ultrasonic intensity.

Arrow in legend indicate this micro-fluidic chip its when actual motion, driven by pressure at two ends difference, its test liquid The flow direction of stream.

Fig. 1 is depicted without the associate members such as described higher-order of oscillation electric signal generator.

Involved miniature ultrasonic transducer units 4 is commercially available；Can also customize to ultrasonic transducer producer.

Involved higher-order of oscillation electric signal transmission cable 3 is commercially available；Can also customize to ultrasonic transducer producer.

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.

Claims (5)

1. relying on interphase interface characteristic to reach the micro flow control chip device of test liquid streaming, the structure of this device includes micro-fluidic core Sheet, the structure of this micro-fluidic chip includes bonded to each other being installed in substrate together and cover plate, its sample liquid stream of this micro-fluidic chip Sample introduction end is located remotely from each other with the terminal of this sample fluid flow, and the distance between this sample introduction end and this terminal is between 3 centimetres and 10 Between centimetre, it is characterised in that its material of this substrate is polydimethylsiloxane material, 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 should The surface of the primary form of material, the structure of this device also includes miniature ultrasonic transducer units, and, higher-order of oscillation electric signal passes Transmission cable, one end of this higher-order of oscillation electric signal transmission cable links together with this miniature ultrasonic transducer units, this miniature ultrasonic Wave transducer is installed in the cover plate of this micro-fluidic chip or the position of the neighbouring described terminal of substrate with attaching；This miniature ultrasonic changes Can its major function of device be when micro-fluidic chip actual sample introduction test, utilize its ultrasound wave launched to reduce sample solution and 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 with And the distance difference between described terminal and this miniature ultrasonic transducer units installation position and its ultrasonic intensity experienced On difference, difference between its interfacial tension of sample introduction end and its interfacial tension of described terminal described in induced synthesis, this micro-fluidic core Interfacial tension difference between these two ends of sheet can form pressure gap, this pressure gap meeting between these two ends of this micro-fluidic chip Drive sample solution to described end flow；Its function of this miniature ultrasonic transducer units also includes checking with its ultrasound wave launched Its absorption on its inner passage inner surface of this micro-fluidic chip of biomacromolecule contained in sample, so check this poly-two Its body of the substrate of methylsiloxane material is relative to the effect of swallowing up of this biomacromolecule；Softness also has this elastic polydimethylsiloxanes Its function of the substrate of alkane material includes, with the character of its absorption strong to ultrasound wave, strongly absorbing ultrasound wave, and thereby existing This terminal of this micro-fluidic chip is to the rapid decrement realizing ultrasonic intensity within the limited short distance between this sample introduction end.

Support interphase interface characteristic the most according to claim 1 reaches the micro flow control chip device of test liquid streaming, and it is special Levying and be, its material of described cover plate is polydimethylsiloxane material.

Support interphase interface characteristic the most according to claim 1 reaches the micro flow control chip device of test liquid streaming, and it is special Levying and be, described cover plate and its thickness of substrate are all between 1.0 millimeters and 5.0 millimeters.

Support interphase interface characteristic the most according to claim 1 reaches the micro flow control chip device of test liquid streaming, and it is special Levying and be, the structure of this device also includes higher-order of oscillation electric signal generator, described higher-order of oscillation electric signal transmission cable its another End is connected with this higher-order of oscillation electric signal generator.

Support interphase interface characteristic the most according to claim 1 reaches the micro flow control chip device of test liquid streaming, and it is special Levying and be, its specified ultrasonic emitting power of this miniature ultrasonic transducer units is between 2 milliwatts and 9000 milliwatts, and this is miniature The frequency of its ultrasound wave operationally launched of ultrasonic transducer is between 100KHz and 12MHz.