CN109603937A - A kind of micro-fluidic chip and its preparation process - Google Patents

A kind of micro-fluidic chip and its preparation process Download PDF

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Publication number
CN109603937A
CN109603937A CN201811652661.7A CN201811652661A CN109603937A CN 109603937 A CN109603937 A CN 109603937A CN 201811652661 A CN201811652661 A CN 201811652661A CN 109603937 A CN109603937 A CN 109603937A
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CN
China
Prior art keywords
preparation process
pdms
micro
chip
processing
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Pending
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CN201811652661.7A
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Chinese (zh)
Inventor
郑世阳
黄蓓
王磊
周庭波
吴志学
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Guizhou Zhongke Jiu Biological Technology Co Ltd
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Guizhou Zhongke Jiu Biological Technology Co Ltd
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Priority to CN201811652661.7A priority Critical patent/CN109603937A/en
Publication of CN109603937A publication Critical patent/CN109603937A/en
Pending legal-status Critical Current

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502707Containers 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 characterised by the manufacture of the container or its components
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/12Specific details about materials

Abstract

The invention discloses a kind of micro-fluidic chip and its preparation processes, it is related to experimental equipment technical field, specifically, the preparation process uses cutting die by PDMS film Punching Technology for the mirofluidic chip with microchannel, and especially for the mirofluidic chip for encountering big, complex dense the micro-channel structure of depth-to-width ratio, the runner being punched into is more regular, forming degree is high, and the substrate rule being punched into is unlikely to deform, which has high production efficiency, the advantage that yield is big and quality is stable.

Description

A kind of micro-fluidic chip and its preparation process
Technical field
The present invention relates to experimental equipment technical fields, in particular to a kind of micro-fluidic chip and its preparation process.
Background technique
Micro-fluidic chip (microscale experiment room) is for traditional macroscopical laboratory, and traditional experiment is by one A little bigger experimental apparatus cooperate with the space occupied by testing come what is completed bigger, and the reagent of consuming is relatively more, time ratio Longer, it is very high to do experimental cost with traditional means of experiment for especially some rare precious reagents.
And the effect of micro-fluidic chip be exactly traditional macro experimental system is miniaturized, it is integrated, using MEMS, Traditional some detections can be integrated in complete in a very small system by the relevant knowledges such as hydrodynamics, chemistry, biology At, accelerate detection time, reduce amount of reagent, improves accuracy, and facilitate combination since system becomes very little, it can be disposable The detection for just doing many projects improves the flux of one-time detection, realizes high-throughput detection.
The advantage of micro-fluidic chip is allowed to be promoted in R&D units, but its industrialized manufacture be in progress always it is slow Slowly, because the state of miniature processing and manufacturing and fluid has bigger difference with macroscopical, tightened up, cost is required in technique It is high.
Current micro-fluidic chip processing technology mainly has micromachined, micro- injection molding, hot pressing, PDMS to reprint, plastic uptake etc.. It is that PDMS (dimethyl silicone polymer) reprints microfluidic chip technology, this material of PDMS with the immediate prior art of this patent Itself has good biologically inert and chemical inertness, and cost is not also high, in chemical analysis detection and biologic medical context of detection Application prospect is extensive.
Existing PDMS reprints technology, and there are some disadvantages, such as: die manufacturing cost is high, is not durable, and some depths The width stay in place form difficulty of processing narrower than bigger, spacing is larger, and the mold that common lithography process method processes is easy Damage, is unfavorable for industrial application.Secondly, PDMS reprints technical efficiency low, low output, be suitable only for laboratory make scientific researches or The occasion small to dosage demand.
And the PDMS film for reprinting out, due to this material of PDMS high resilience itself, material viscosity is higher, and mobility is not Be it is very good, for the PDMS chip of runner complex dense, planform is not very regular after molding.
It due to the chemical inertness of PDMS film, is not easy to be bonded together with other material, with plasma and some special tables Surface modification process can only also allow the chip of a small number of materials such as itself and other PDMS film, glass, silicon to bond.There are also technologies to be It is first that PDMS membrane DNA chip surface is modified, it is then bonded with 502, AB glue etc., and these glue are Instant cement a bit, are left for subsequent The time for aligning pad pasting is seldom, some are the higher glue of viscosity, can not achieve large area industrialization atomizing spraying, causes gluing thick Degree is uneven, inefficiency.
So needing first to carry out surface modification treatment to PDMS film, but plasma and special surface modification technology are number Tired, state modulator requires stringent, little suitable for industrial.Finally, pad pasting low efficiency, yield is limited, and quality is not easily controlled.
Summary of the invention
The first object of the present invention is to provide a kind of preparation process of micro-fluidic chip, which will using cutting die PDMS film Punching Technology is the mirofluidic chip with microchannel, and especially for encountering, depth-to-width ratio is big, miniflow of complex dense The mirofluidic chip of road structure, the runner being punched into is more regular, and forming degree is high, and the substrate rule being punched into is unlikely to deform, The preparation process has high production efficiency, the advantage that yield is big and quality is stable.
The second object of the present invention is to provide a kind of mirofluidic chip, which has is unlikely to deform for fluid channel is regular The advantages of.
The third object of the present invention is to provide a kind of micro-fluidic chip, which has that fluid channel is regular to be not easy The high advantage of deformation, chip quality.
The present invention is implemented as follows:
The embodiment of the present invention provides a kind of preparation process of micro-fluidic chip comprising has following steps:
The preparation step of binder:
According to parts by weight, the preparation step of binder includes mixing following raw material: 70~90 parts of organosilicons, 10~30 Part calcium carbonate, 0.5~1.0 part of catalyst and 0.5~1.0 part of additive (N/A).After mixing, vacuumizes or centrifugal process is gone Bubble removing is mixed with equipment is mixed, is then encapsulated.
Specifically, binder is silicone sealants, and performance before curing is as shown in table 1, such as table 2 of the performance after solidification It is shown, it should be noted that data are surveyed after solidifying seven days under conditions of 25 DEG C, relative humidity 55% in table.
The performance before curing of table 1
Project Unit Parameter value Detection method
Appearance —— Transparency liquid Visually
Density g/cm3 0.8±0.02 GB/T 13354-92
Solid content % 40 GB/T 2793-1995
Viscosity mPa.s 75~95 GB/T 1723-1993
Refractive index —— 1.48~1.50 GB/T6488-2008
Surface drying time min 15~20 Fingers-touch method
Table 2 solidify after performance
General method is directly to be diluted using diluents such as dimethylbenzene, but these diluents are often deposited on the market at present Not environmentally, it is toxic the disadvantages of.The binder that the application uses uses without dilution and changes production silicone sealants Intermediate and synthetic catalyst, be allowed to viscosity reduction, the silicone sealants of this preparation method preparation are more environmentally-friendly.
Further, the present invention uses PDMS coiled material film, is a kind of film made in advance with liquid PDMS raw material, system It is rolled into a roll after standby, convenient transportation and storage.It should be noted that PDMS (polydimethylsiloxanes can also be used or be used Alkane) film preparation step: by PDMS raw material, i.e. PDMS performed polymer is mixed with curing agent according to the volume ratio of 10:1, removes bubble removing Afterwards, solidification obtains PDMS film at 60 DEG C~120 DEG C.It is reprinted in technology in PDMS, needs proportionally to mix PDMS raw material It closes, then PDMS is poured and is cast from mold, be heating and curing at a certain temperature, PDMS material is peeled off from mold and is had There is the mirofluidic chip of microchannel.
But the amount very little of the PDMS due to being needed on each mold, PDMS disposably cannot be largely prepared, is mixed After preparation, if cannot be finished in time, PDMS just gradually solidifies after usual 2h, is no longer available for reprinting, and causes to waste, and causes to adjust The heavy workload of glue, it is time-consuming and laborious.
Therefore, used in the embodiment of the present invention is that PDMS film is processed into miniflow by the way of cutting die punching The PDMS substrate in road.It should be noted that in some embodiments of the invention, PDMS film directlys adopt PDMS volumes prepared Material.
The procedure of processing of PDMS film:
Cutting die is fixed on work bench of punch press, punching parameter is set according to punching demand, by raw material PDMS coiled material film Be placed on roller tensioning transmission device, using roller tensioning transmission device raw material PDMS film be transported to punch plunger chip and cutting die it Between.
If desired set position punching on punching machine install additional set position device, then start punching machine work, can continuously and automatically by PDMS film is punched into the mirofluidic chip of various flow channel shapes, and this substrate neat appearance facilitates subsequent contraposition pad pasting.Punching machine There is automatic counting function, can largely be produced according to the parameter of setting.It should be noted that set position device is mainly for complexity Flow passage structure.
The processing technology of cutting die is quite mature, in procedure of processing, is designed according to the complexity and concentration of runner At one-step punching cutting die, the set position punching cutter of position punching cutter or more numbers is covered twice.Preferably, it is punched using 1 time Cutter processes runner.
Big, complex dense the flow passage structure especially for depth-to-width ratio, the method that cutting die is punched using set position, primary punching Shear reduces cutting die difficulty of processing at the limitation of small space structure several times, is thus avoided, while guaranteeing the quality of punching. Cutting die steel of the cutting die material using profession, long service life.
Sealing-in step:
After PDMS substrate processes, pasted according to the cover plate of the design and various materials of micro-fluidic chip by binder glue spraying It is combined.
It is different from the PDMS film micro-fluidic chip reprinted, the micro-fluidic base of preparation process preparation provided in an embodiment of the present invention It is modified that piece does not need surface before gluing.Mirofluidic chip and micro-fluidic cover plate can be sealed using binder. It is flexible after binder solidification, it will not be hardened because of glue curing, PDMS membrane stress is caused to deform.
Further, sealing-in step can have different-thickness, no for two layers or more as made from PDMS procedure of processing Mirofluidic chip glue spraying with micro-channel structure is bonded to form compound mirofluidic chip.Compound mirofluidic chip can satisfy more Add the demand of complicated micro-channel structure.
Further, in embodiments of the present invention, it is preferred to use binder is sprayed at micro-fluidic by the mode of atomizing spraying On substrate or micro-fluidic cover plate, the coating thickness of binder is controllable, and coating thickness is mainly by the performance of glue sprayer and binder Viscosity determines that binder viscosity is lower, and what can be sprayed is thinner, and more uniform, glue sprayer performance is better, can control the glue of ejection More evenly, thinner.General 0.01 ㎜ or more of coating thickness.
After glue spraying, mirofluidic chip or compound mirofluidic chip are attached on micro-fluidic cover plate using laminator.Automatically Laminator is high-efficient, and pad pasting quality is high and stablizes, and waits binder after 20h~30h to solidify, can be completed.
PDMS reprints that the PDMS membrane DNA chip shape that chip technology manufactures is not regular enough, and scale error is big, can not with from Shape is accurately positioned in dynamic laminator or jig, can only manual alignment, low efficiency, fitting quality is difficult effectively to control. New process cutting die is punched into the PDMS membrane DNA chip shape rule come, and scale error is small, facilitates and is positioned with automatic film applicator and jig, Pad pasting is high-efficient, and fitting quality is stablized.
A kind of mirofluidic chip is processed by the procedure of processing of PDMS film in above-mentioned preparation process and is made.
A kind of micro-fluidic chip is made by above-mentioned preparation process.
The invention has the following advantages:
The present invention provides a kind of preparation process of micro-fluidic chip, which is added the punching of PDMS film using cutting die Work is the mirofluidic chip with microchannel, especially for the miniflow for encountering big, complex dense the micro-channel structure of depth-to-width ratio Substrate is controlled, the runner being punched into is more regular, and forming degree is high, and the substrate rule being punched into is unlikely to deform, preparation process tool There is high production efficiency, the advantage that yield is big and quality is stable.
The present invention also provides a kind of mirofluidic chip and micro-fluidic chip, which has fluid channel regular It is unlikely to deform, the advantage that chip quality is high.
Specific embodiment
It in order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below will be in the embodiment of the present invention Technical solution be clearly and completely described.The person that is not specified actual conditions in embodiment, according to normal conditions or manufacturer builds The condition of view carries out.Reagents or instruments used without specified manufacturer is the conventional production that can be obtained by commercially available purchase Product.
Feature and performance of the invention are described in further detail with reference to embodiments.
Embodiment 1
The embodiment of the present invention provides a kind of preparation process of micro-fluidic chip comprising has following steps:
The preparation step of binder:
According to parts by weight, the preparation step of binder includes mixing following raw material: 80 parts of organosilicon (70131-67- 8), 20 parts of calcium carbonate (471-34-1), 1.0 parts of catalyst (68611-44-9) and 1.0 parts of additives (N/A).After mixing, take out Vacuum or centrifugal process remove bubble removing, are mixed with equipment is mixed, are then encapsulated.
The procedure of processing of PDMS film:
Cutting die is fixed on work bench of punch press, punching parameter is set according to punching demand:
For the PDMS film of 0.2mm thickness, film thickness 0.2mm adds the total 0.3mm of protective layer thickness 0.1mm, and setting punching machine impacts 500 kilograms of power, setting Z axis coordinate is 0 when punch plunger chip has just touched cutting die pressing plate, then 0.32mm is rushed again downwards, punching The waste material to get off is drained by the chip-removal hole of cutting die, and fluid channel can be punched on film.
Raw material PDMS film is placed on roller tensioning transmission device, raw material PDMS film is transported using roller tensioning transmission device It is sent between punch plunger chip and cutting die.
It covers position punching and installs set position device additional on punching machine, then start punching machine work, be continuously and automatically punched PDMS film The mirofluidic chip of various flow channel shapes out.In procedure of processing, it is designed to cover twice according to the complexity and concentration of runner Position punching cutter.
Sealing-in step:
After PDMS substrate processes, existed according to the design of micro-fluidic chip and the cover plate of various materials by binder sealing-in Together.
Specifically, binder is sprayed on mirofluidic chip or micro-fluidic cover plate by the way of atomizing spraying, is bonded The coating thickness of agent is 0.02mm,.
After glue spraying, using laminator automatic coating.Automatic film applicator is high-efficient, and pad pasting quality is high and stablizes, and glues after waiting 20h Tie agent solidification, it should be noted that in other embodiments, toast 1~3 hour with 30~40 DEG C to accelerate curing rate, contract Short curing time.
Embodiment 2
The embodiment of the present invention provides a kind of preparation process of micro-fluidic chip, and the preparation process provided with embodiment 1 is big Cause identical, difference is the difference of parameter, it distinguishes as follows:
The preparation step of binder is same as above.
The procedure of processing of PDMS film:
Cutting die is fixed on work bench of punch press, punching parameter is set according to punching demand:
Such as the PDMS film of 0.3 millimeters thick, 0.3 millimeter of film thickness adds totally 0.4 millimeter of 0.1 millimeter of protective layer thickness, 500 kilograms of punching machine impact force of setting, setting Z axis coordinate is 0 when punch plunger chip has just touched cutting die pressing plate, is then rushed again downwards 0.42 millimeter, the waste material that punching is got off is drained by the chip-removal hole of cutting die, fluid channel can be punched on film.
Raw material PDMS film is placed on roller tensioning transmission device, raw material PDMS film is transported using roller tensioning transmission device It is sent between punch plunger chip and cutting die.It covers position punching and installs set position device additional on punching machine, then start punching machine work, it is continuous automatic The mirofluidic chip that PDMS film is punched into various flow channel shapes.
In procedure of processing, it is designed to cover a punching cutter three times according to the complexity and concentration of runner.
Sealing-in step:
After mirofluidic chip processes, mirofluidic chip and the cover plate of various materials are led to according to the design of micro-fluidic chip Binder is crossed to seal.
Specifically, binder is sprayed on mirofluidic chip or micro-fluidic cover plate by the way of atomizing spraying, is bonded The coating thickness of agent is 0.01mm,.
After glue spraying, using laminator automatic coating.Automatic film applicator is high-efficient, and pad pasting quality is high and stablizes, 40 DEG C of bakings 3 Hour solidification binder, can be completed.
Comparative example 1
Verify the performance for the preparation process that embodiment 1,2 provides.
Micro-fluidic chip is prepared using the preparation process that embodiment 1,2 provides, (existing PDMS reprints skill with the prior art Art) micro-fluidic chip be compared, comparison result is as shown in table 3.
3 comparison result of table
As shown in Table 3, in terms of existing technologies, preparation process provided in this embodiment can be with low-cost and high-quality Mode produce micro-fluidic chip.
To sum up, the present invention provides a kind of preparation process of micro-fluidic chip, which uses cutting die by PDMS film Punching Technology is the mirofluidic chip with microchannel, and especially for encountering, depth-to-width ratio is big, micro-channel structure of complex dense Mirofluidic chip, the runner being punched into is more regular, and forming degree is high, and the substrate rule being punched into is unlikely to deform, the preparation Technique has high production efficiency, the advantage that yield is big and quality is stable.
The present invention also provides a kind of mirofluidic chip and micro-fluidic chip, which has advises for fluid channel It is whole be unlikely to deform, the advantage that chip quality is high.
The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention, for the skill of this field For art personnel, the invention may be variously modified and varied.All within the spirits and principles of the present invention, made any to repair Change, equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.

Claims (10)

1. a kind of preparation process of micro-fluidic chip, which is characterized in that it includes the procedure of processing of PDMS film;The PDMS film Procedure of processing includes using cutting die by PDMS film Punching Technology for the mirofluidic chip with microchannel.
2. preparation process according to claim 1, which is characterized in that in the PDMS film procedure of processing, the punching Processing includes the processing of one-step punching cutting die or the processing of time position punching cutter.
3. preparation process according to claim 1 or 2, which is characterized in that the preparation process is processed in the PDMS and walked It include sealing-in step after rapid;
The sealing-in step includes being bonded mirofluidic chip made from PDMS procedure of processing with micro-fluidic cover plate sealing-in.
4. preparation process according to claim 3, which is characterized in that the sealing-in step includes:
By two layers or two layers or more the fitting of the mirofluidic chip glue spraying as made from PDMS procedure of processing to form compound micro-fluidic base Then the compound mirofluidic chip is bonded by piece with micro-fluidic cover plate sealing-in.
5. preparation process according to claim 3, which is characterized in that the sealing-in step includes the side using atomizing spraying Binder is sprayed on PDMS film substrate or micro-fluidic cover plate by formula.
6. preparation process according to claim 5, which is characterized in that before the sealing-in step, the preparation process packet Include the preparation step of binder;
According to parts by weight, the preparation step of the binder includes mixing following raw material: 70~90 parts of organosilicons, 10~30 Part calcium carbonate, 0.5~1.0 part of catalyst and 0.5~1.0 part of additive.
7. preparation process according to claim 3, which is characterized in that selected in the procedure of processing of the PDMS film PDMS film be PDMS coiled material.
8. preparation process according to claim 7, which is characterized in that the thickness of the PDMS film is greater than 0.01mm.
9. a kind of mirofluidic chip, which is characterized in that its PDMS film as described in preparation process of any of claims 1 or 2 Procedure of processing processing is made.
10. a kind of micro-fluidic chip, which is characterized in that it is made by preparation process according to any one of claims 1 to 8.
CN201811652661.7A 2018-12-29 2018-12-29 A kind of micro-fluidic chip and its preparation process Pending CN109603937A (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060202330A1 (en) * 2005-03-11 2006-09-14 Agilent Technologies, Inc. Chip with cleaning cavity
CN102861622A (en) * 2012-09-21 2013-01-09 武汉介观生物科技有限责任公司 Micro-fluidic chip interface base on basis of vacuum absorption micro-sealing and manufacturing method for micro-fluidic chip interface base
CN103962192A (en) * 2014-04-11 2014-08-06 兰州大学 Preparation method of high molecular polymer micro-fluidic chip
CN104475177A (en) * 2014-12-02 2015-04-01 武汉纺织大学 Method for preparing simple high-bonding-strength polymer microflow chip
CN107159330A (en) * 2017-06-09 2017-09-15 北京百康芯生物科技有限公司 A kind of diaphragm type nucleic acid amplification micro-fluidic chip and preparation method thereof
CN107709992A (en) * 2015-04-30 2018-02-16 新加坡科技研究局 The new design and its application method of enzyme linked immunosorbent assay (ELISA) plate and system

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060202330A1 (en) * 2005-03-11 2006-09-14 Agilent Technologies, Inc. Chip with cleaning cavity
CN102861622A (en) * 2012-09-21 2013-01-09 武汉介观生物科技有限责任公司 Micro-fluidic chip interface base on basis of vacuum absorption micro-sealing and manufacturing method for micro-fluidic chip interface base
CN103962192A (en) * 2014-04-11 2014-08-06 兰州大学 Preparation method of high molecular polymer micro-fluidic chip
CN104475177A (en) * 2014-12-02 2015-04-01 武汉纺织大学 Method for preparing simple high-bonding-strength polymer microflow chip
CN107709992A (en) * 2015-04-30 2018-02-16 新加坡科技研究局 The new design and its application method of enzyme linked immunosorbent assay (ELISA) plate and system
CN107159330A (en) * 2017-06-09 2017-09-15 北京百康芯生物科技有限公司 A kind of diaphragm type nucleic acid amplification micro-fluidic chip and preparation method thereof

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Application publication date: 20190412