CN105396631B - A kind of three-dimensional micro-fluidic chip and preparation method thereof - Google Patents
A kind of three-dimensional micro-fluidic chip and preparation method thereof Download PDFInfo
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- CN105396631B CN105396631B CN201510919760.7A CN201510919760A CN105396631B CN 105396631 B CN105396631 B CN 105396631B CN 201510919760 A CN201510919760 A CN 201510919760A CN 105396631 B CN105396631 B CN 105396631B
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Abstract
The invention discloses a kind of three-dimensional micro-fluidic chip, including the first substrate, second substrate, ... to N substrates, N is the positive integer more than or equal to 2, and first substrate to N substrates has microchannel or miniflow chamber, and first substrate passes sequentially through polymeric layer to N substrates and connected two-by-two, so that the microchannel or miniflow chamber of first substrate to N substrates are connected, so as to form the micro-fluidic structure of solid.The invention also discloses the preparation method of the micro-fluidic chip, prefabricated polymer uniform is coated on substrate first, 1 μm~100 μm of polymeric layer is obtained after drying；Then the first substrate and the second substrate are bonded with polymeric layer respectively, are superimposed repeatedly, so as to obtain the micro-fluidic chip.By the present invention, the bonding of micro-fluidic chip is realized in the case where not applying pressure, method is simple, can be widely applied to the preparation of micro-fluidic chip.
Description
Technical field
The invention belongs to micro-fluidic chip field, more particularly, to a kind of three-dimensional micro-fluidic chip and its preparation side
Method.
Background technology
Micro flow chip is the core of micro-total analysis system, and chemistry, food, environment, doctor are given in the invention and application of micro flow chip
Learn etc. scientific domain provide great convenience, promoted some analyze be miniaturized, it is integrated, automation and facilitation.Greatly
Big saves some consumption chemically reacted to valuable chemical reagent, also greatly improves analysis efficiency, reduces expense.
The material of micro-fluidic chip has polymer, such as PDMS (dimethyl silicone polymer), PMMA (poly-methyl methacrylates
Ester) etc., also there are hard material, such as sheet glass, quartz plate etc..Polymeric material can be prepared by mask method or 3d impact systems
Microchannel, the moulding free degree is high, but it has and is easily deformed, the characteristics of easy absorbing organic solvent, its analysis precision
It can not show a candle to the micro-fluidic chip of hard material.Although hard material performance is stable, analysis precision is high, and moulding and bonding is then relative
It is difficult.
It can be engaged the micro-fluidic structure of hard substrate by being superimposed double-deck hard substrate in the prior art, so that
Relative complex three-dimensional micro-fluidic structure is produced, but the bonding method of hard substrate only has low-temperature bonding method and glue at present
Bonding；Wherein, low-temperature bonding method can only be directed to glass-chip, and have high requirements to the smooth clean-up performance of glass surface, need
Want cumbersome cleaning；And gluing, such as patent document CN103263950A disclose a kind of micro-fluidic core of glass base heterozygosis
The preparation method of piece, layer glass substrate is combined using double faced adhesive tape, and double faced adhesive tape not only easily blocks micro- ditch in adhesion process
Road is, it is necessary to longer hardening time, and bonding loosely and easily comes off during use.
The content of the invention
For the disadvantages described above or Improvement requirement of prior art, the invention provides a kind of three-dimensional micro-fluidic chip and its
Preparation method, its object is to connect hard substrate by polymeric layer, forms three-dimensional micro-fluidic chip, so as to avoid micro-
Fluidic chip contamination and plugging micro-fluidic structure in adhesion process, so as to influence the performance of chip.
To achieve the above object, according to one aspect of the present invention there is provided a kind of micro-fluidic chip, including the first base
Piece, the second substrate ... to N substrates, N is the positive integer more than or equal to 2, and there is first substrate to N substrates miniflow to lead to
Road or microfluidic chambers, first substrate pass sequentially through polymeric layer to N substrates and connected two-by-two so that the miniflow of adjacent substrates leads to
Road or microfluidic chambers are connected, so as to form the micro-fluidic structure of solid.
Preferably, the material of the polymeric layer is dimethyl silicone polymer, polyethylene or polyurethane.
Preferably, the thickness of the polymeric layer is 1 μm~5mm.
As it is further preferred that the thickness of the polymeric layer is 1 μm~100 μm.
As it is further preferred that the thickness of the polymeric layer is 1 μm~20 μm.
Preferably, first substrate to N substrates are sheet glass, silicon chip or quartz plate.
It is another aspect of this invention to provide that there is provided a kind of preparation method of the micro-fluidic chip, comprising the following steps：
(1) design and prepare the first substrate, the second substrate ... to N substrates so that first substrate to N bases
Piece has the microchannel cooperated or microfluidic chambers, and N is the positive integer more than or equal to 2；
(2) prefabricated polymer uniform is coated in flexible substrate, the smooth polymerization of thickness needed for being obtained after solidification
Nitride layer；
(3) surface of the first substrate is bonded with the polymeric layer in the flexible substrate, then removes the smooth lining
Bottom, makes the polymeric layer indwelling in the surface of the first substrate；Remove the microchannel or microfluidic chambers of first substrate surface
The polymeric layer of upper covering, then the polymeric layer by the surface of the second substrate with indwelling in the first substrate surface be bonded,
So that first substrate is connected with second substrate by polymeric layer, both microchannels or microfluidic chambers are connected；
Above-mentioned steps are repeated in, until first substrate passes sequentially through polymeric layer to N substrates and connected two-by-two, and adjacent substrates
Microchannel or microfluidic chambers be connected so that constitute solid micro-fluidic chip.
Preferably, the flexible substrate is polyethylene terephthalate glued membrane, ethylene-vinyl acetate copolymer adhesive film
Or TPUE glued membrane.
Preferably, the method for coating is spin-coating method or print process in the step (1).
Preferably, the method for bonding is legal for hot key in the step (3).
In general, by the contemplated above technical scheme of the present invention compared with prior art, due to passing through polymer
Layer connection substrate can obtain following beneficial effect so as to form micro-fluidic chip：
1st, mutually combined closely by polymeric layer between substrate, its bonding process need not apply pressure, so as to reduce
The deformation of the micro-fluidic chip of preparation, improves the probability being successfully prepared；
2nd, different from the cohesive material on double faced adhesive tape surface, polymeric layer is solid material, easily removes, will not prepare
Microfluidic channel is blocked in journey；
3rd, multi layer substrate can be connected by polymeric layer so that bilevel micro-fluidic structure is communicated, so as to make
Relative complex three-dimensional micro-fluidic structure is produced, the functional areas of micro-fluidic chip are increased；
4th, polymeric layer is prepared on flexible substrates, not only make it that polymeric layer is smooth, is not interfered with prepare micro-
The structure of fluidic chip, can also arbitrarily control the thickness of polymeric layer according to demand；
5th, by flexible substrate transfer polymerization nitride layer, not only prevent polymeric layer from being crushed in transfer process, be also prevented from
Polymeric layer produces deformation during transfer, further optimizes the performance of micro-fluidic chip；
6th, the preparation method of the micro-fluidic chip is simple, and bond strength is high, with good practicality.
Brief description of the drawings
Fig. 1 is the preparation method flow chart of the embodiment of the present invention 1；
Fig. 2 a are the substrate of the embodiment of the present invention 2 first, the second substrate and the 3rd substrate structure schematic diagram；
Fig. 2 b are the microfluidic chip structure schematic diagrames of the embodiment of the present invention 2；
In all of the figs, identical reference is used for representing identical element or structure, wherein, 1- glued membranes, 2- gathers
Compound layer, the substrates of 3- first, the substrates of 4- second, the substrates of 5- the 3rd.
Embodiment
In order to make the purpose , technical scheme and advantage of the present invention be clearer, it is right below in conjunction with drawings and Examples
The present invention is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, and
It is not used in the restriction present invention.As long as in addition, technical characteristic involved in each embodiment of invention described below
Not constituting conflict each other can just be mutually combined.
The invention discloses a kind of micro-fluidic chip, including the first substrate, the second substrate ... to N substrates, N be more than
Positive integer equal to 2, first substrate to N substrates has micro-fluidic structure, and first substrate to N substrates passes through 1 μ
M~5mm smooth polymeric layer connection so that the micro-fluidic structure of first substrate to the N substrates is connected, so that shape
Into three-dimensional micro-fluidic structure.Because hard substrate performance is stable, it is unlikely to deform, and with more preferable precision, first base
Piece is to the hard substrate that N substrates are that surface has hydrophilic radical, and such as sheet glass, surface has the silicon chip or quartz of silicon dioxide layer
Piece.The polymer is dimethyl silicone polymer (PDMS), low density polyethylene (LDPE) (PE) or TPUE (TPU)
Deng easily polymerizeing at normal temperatures, and the high polymer material that can be bonded with hard substrate.Because polymeric layer is thinner, micro-fluidic chip
Deformation is smaller, and performance is more excellent, and the thickness of polymeric layer is preferably 1 μm~100 μm, is still more preferably 1 μm~20 μm.
The preparation method of the micro-fluidic chip comprises the following steps：
(1) (it is usually the mixture of polymer monomer and crosslinking agent, the mixture normal temperature or heating by prefabricated polymer
Solidification can obtain polymer) it is evenly applied to spin-coating method or print process etc. in smooth substrates, normal temperature or after being heating and curing
To 1 μm~5mm polymeric layer；By controlling preparation technology, the controllable thickness for obtaining polymeric layer, for example, using spin-coating method
When preparing polymeric layer, using 1500r/min rotating speed rotate 35 seconds can must be about 20 μm polymeric layer, and rotating speed is higher, in advance
The concentration of the polymer of system is smaller, and rotational time is longer, then polymeric layer is thinner, and when utilizing print process, hole pattern is thinner, then makes
Standby obtained polymeric layer is also thinner；And the selection of substrate is relevant with the thickness of required polymeric layer, when the thickness of polymeric layer
Degree is more than 100 μm, and using smooth hard material (such as glass, silicon chip) as substrate, polymeric layer is removed into rear and substrate
Bonding, and when the thickness of polymeric layer is less than 100 μm, then preferred flexible substrate, such as polyethylene terephthalate
(PET) glued membrane, the material such as ethylene-vinyl acetate copolymer glue (EVA) film or TPUE (TPU) glued membrane, with
Reduce deformation of the polymeric layer in transfer process, while avoiding polymeric layer damaged in transfer process；
(2) polymeric layer is bonded with the first substrate, then taken smooth substrates off, or first taken from smooth substrates
Lower polymeric layer, then be bonded with the first substrate, the polymeric layer is residued in the first substrate surface；Bonding method can be heat
Bonding method, oxygen plasma etc.；
(3) polymeric layer covered on the first substrate surface micro-fluidic structure is removed, by the surface of the second substrate and institute
State the another side bonding of polymeric layer so that first substrate is connected with second substrate by polymeric layer, so that group
Into the micro-fluidic chip.If micro-fluidic chip has more than three layers of structure, repeat step (2) and step (3) are needed,
So that first substrate to N substrates pass sequentially through polymeric layer connection, so as to constitute the micro-fluidic chip, N be more than
Positive integer equal to 3.
For the micro-fluidic chip of structure needed for preparing, first it can design and etch to N substrate higher slices in the first substrate
Microchannel or microfluidic chambers needed for going out, when the first substrate to N substrates passes sequentially through polymeric layer connection, it is necessary to by needs
The micro-fluidic structure alignment of connection is bonded again so that the microchannel or microfluidic chambers of the first substrate to the N substrates are mutual
It is connected, and forms the micro-fluidic structure of solid.
Embodiment 1
A kind of micro-fluidic chip, is made up of, the surface of the first substrate and the second substrate passes through the first substrate and the second substrate
5mm polymeric layer connection, the preparation method of the chip is as shown in Figure 1：
1) base chip is prepared：
Two panels silicon chip is chosen as substrate, and processing obtains required micro-fluidic structure on silicon chip, then uses deionization
Water rinses chip, removes the impurity such as substrate surface greasy dirt, particulate matter, is put into the thermal station of clean workspace and dries after cleaning up
It is standby.
2) polymer is prepared：
Polymer described here is PDMS.By PDMS elastomers and PDMS curing agent according to 10:1 ratio adds dixie cup
In, mixed liquor is then stirred in one direction with clean glass bar, until uniform minute bubbles are presented in mixed liquor, then will
The mixed liquor being stirred, which is stood to bubble, to be completely eliminated.
3) glued membrane is prepared：
It is EVA adhesive film 1 used herein of substrate.Press the glued membrane principle shearing glued membrane bigger than base chip size, Ran Houyong
Deionized water cleans glued membrane, until can't see chromatic pattern against light and do not hang water, clean film then is put into clean work
Make to dry in the thermal station in area, thermal station temperature is 65 degrees Celsius, and the time is about half an hour.
4) overlay film is operated：
The PDMS prepared is laid down into the surface of EVA adhesive film 1,5mm polymeric layer 2 is formed.
5) pre- bonding operation：
First substrate 3 and polymeric layer 2 are respectively put into corona box, corona is carried out under power 2.5KW, when it is a length of
120 seconds.After the completion of corona, the first substrate 3 is fitted with polymeric layer 2, then that the chip posted is put into thermal station is enterprising
Row thermal bonding, thermal station temperature is 65 degrees Celsius, hot key and after about 5 hours, removal EVA adhesive film 1.
6) bonding operation：
First substrate 3 and the second substrate 4 are put into corona box by the polymer removed on the micro-fluidic structure of the first substrate 3,
Wherein it is bonded face-up.Carry out corona under power 2.5kw, when a length of 120s.After the completion of corona, by the second substrate 4 and first
After the micro-fluidic structure alignment of substrate 2, fitted with the another side of polymeric layer, it is enterprising that the chip posted then is put into thermal station
Row thermal bonding, that is, obtain the micro-fluidic chip.
Embodiment 2
1) base chip is prepared：
Three sheet glass chips are chosen respectively as the first substrate, the second substrate and the 3rd substrate, and are processed respectively micro-
Flow structure, as shown in Figure 2 a, sequentially consists of the first substrate 3, the second substrate 4 and the 3rd substrate 5.Then deionization is used
Water rinses chip, removes the impurity such as substrate surface greasy dirt, particulate matter, is put into the thermal station of clean workspace and dries after cleaning up
It is standby.
2) glued membrane is prepared：
Glued membrane described here is PET glued membranes.Press glued membrane it is bigger than base chip size principle shearing glued membrane, then spend from
Sub- water cleans glued membrane, until can't see chromatic pattern against light and do not hang water, clean film then is put into clean workspace
Thermal station on dry, thermal station temperature be 65 degrees Celsius, the time is about half an hour.
3) polymer is prepared：
Polymer described here is PDMS.By PDMS elastomers and PDMS curing agent according to 11:1 ratio adds dixie cup
In, mixed liquor is then stirred in one direction with clean glass bar, until uniform minute bubbles are presented in mixed liquor, then will
The mixed liquor being stirred, which is stood to bubble, to be completely eliminated.
4) overlay film is operated：
The PDMS prepared is poured on the glued membrane prepared, glued membrane is then placed on the center spin coating of sol evenning machine sucker, it is even
Glue machine rotating speed is 1500r/min, when a length of 35 seconds, it is 20 μm of PDMS polymeric layers to obtain thickness.Then it will be covered with PDMS
Glued membrane take out be put into thermal station dry, thermal station temperature be 65 degrees Celsius, the time is about 1 hour.Note whole operation Ying Jie
Completed in net working environment.
5) pre- bonding operation：
The bonding of first substrate 3 and glued membrane is put into corona box up, corona, duration are carried out under power 2.5KW
For 120 seconds.After the completion of corona, chip is fitted with PDMS films, then the chip posted is put into thermal station carries out hot key
Close, thermal station temperature is 65 degrees Celsius, hot key and about 5 hours.
6) bonding operation：
With blade along pass through step 5) processing the first substrate edge cut PDMS films, then glued membrane is taken off, gone
Except the polymeric layer of substrate surface through hole.The first substrate and the second substrate chip that will be covered with PDMS films are put into corona box
In, wherein bonding is face-up.Carry out corona under power 2.5kw, when a length of 120s.After the completion of corona, by the first substrate surface
PDMS films and the second substrate bonding face on micro-fluidic structure alignment laminating, then the chip posted is put into thermal station
Carry out thermal bonding.
7) repeat step 5) and 6), the 3rd substrate is obtained again by PDMS film combinations in another surface of the second substrate
The microfluidic chip structure arrived as shown in Figure 2 b, forms the micro-fluidic structure of solid.
It can be designed with similar method and produce increasingly complex three-dimensional micro-fluidic chip, for example, can be not
The microfluidic channel with difference in functionality is designed on same substrate, fluid is passed sequentially through different microfluidic channels and carries out instead
Should, air pump and air valve are can be combined with, reaction is controllably carried out.
As it will be easily appreciated by one skilled in the art that the foregoing is merely illustrative of the preferred embodiments of the present invention, it is not used to
The limitation present invention, any modifications, equivalent substitutions and improvements made within the spirit and principles of the invention etc., it all should include
Within protection scope of the present invention.
Claims (4)
1. a kind of preparation method of micro-fluidic chip, it is characterised in that comprise the following steps：(1) design and prepare the first base
Piece, the second substrate ... to N substrates so that first substrate to N substrates has the microchannel or miniflow cooperated
Room, N is the positive integer more than or equal to 2, and first substrate to N substrates is sheet glass, silicon chip or quartz plate；(2) will be prefabricated
Polymer uniform be coated in flexible substrate, 1 μm~100 μm of polymeric layer is obtained after solidification；(3) by the table of the first substrate
Face is bonded with the polymeric layer in the flexible substrate, then removes the flexible substrate, makes the polymeric layer indwelling in
The surface of one substrate；The polymeric layer covered on the microchannel or microfluidic chambers of first substrate surface is removed, then by
The polymeric layer of the surface of two substrates with indwelling in the first substrate surface is bonded so that first substrate and described second
Substrate is connected by polymeric layer；Above-mentioned steps are repeated in, until first substrate to N substrates pass sequentially through polymer
Layer is connected two-by-two so that the microchannel or microfluidic chambers of adjacent substrates are connected, so as to constitute the micro-fluidic chip of solid.
2. preparation method as claimed in claim 1, it is characterised in that the flexible substrate is polyethylene terephthalate
Glued membrane, ethylene-vinyl acetate copolymer adhesive film or TPUE glued membrane.
3. preparation method as claimed in claim 1, it is characterised in that in the step (2) method of coating for spin-coating method or
Print process.
4. preparation method as claimed in claim 1, it is characterised in that the method for bonding is legal for hot key in the step (3).
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| CN105749994B (en) * | 2016-04-23 | 2017-12-15 | 北京化工大学 | A kind of three-dimensional microflow control chip preparation method of plural layers fitting |
| CN107159332A (en) * | 2017-06-22 | 2017-09-15 | 武汉大学 | A kind of micro-fluidic bulk wave sorting chip preparation method based on silica gel bonded layer |
| CN107715930B (en) * | 2017-09-22 | 2020-03-17 | 华中科技大学同济医学院附属协和医院 | Chip structure |
| CN112569881B (en) * | 2020-07-24 | 2021-07-20 | 苏州恒瑞宏远医疗科技有限公司 | Reaction device and processing method thereof |
| CN113234571B (en) * | 2021-04-29 | 2023-08-25 | 杭州霆科生物科技有限公司 | High-flux enzyme screening chip |
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| JP2009156763A (en) * | 2007-12-27 | 2009-07-16 | Nec Corp | Microchip and analysis method using the same |
| CN102093583B (en) * | 2010-12-02 | 2012-09-26 | 西北工业大学 | Irreversible bonding method using polydimethylsiloxane as substrate material |
| CN102218595B (en) * | 2011-01-14 | 2013-09-11 | 哈尔滨工业大学（威海） | Method for preparing micro-fluidic chip |
| CN102286358B (en) * | 2011-05-31 | 2013-06-19 | 中国科学院合肥物质科学研究院 | Microfluidic control chip for realizing PCR (Polymerase Chain Reaction) and real-time PCR virus quick detection device |
| JP6422197B2 (en) * | 2012-03-13 | 2018-11-14 | 株式会社朝日Ｆｒ研究所 | Method for manufacturing a microchemical chip |
| CN102721820B (en) * | 2012-05-21 | 2013-11-13 | 浙江大学 | Method for preparing assembly type polymer micro fluidic chip equipped with integrated pneumatic micro valve |
| CN102910578B (en) * | 2012-11-07 | 2015-11-18 | 中国科学院上海微系统与信息技术研究所 | A kind of method adopting hybrid plasma to realize silicon base chip and PDMS chip bonding |
| CN103058131B (en) * | 2012-12-19 | 2015-09-16 | 中国科学院上海微系统与信息技术研究所 | A kind of preparation method of high strength reversible keying micro-fluidic chip |
| CN104830683B (en) * | 2015-04-30 | 2017-06-30 | 大连医科大学附属第二医院 | A kind of bionical micro-fluidic chip for simulating interior tumor cell and its transfer microenvironment |
| CN104998702A (en) * | 2015-07-03 | 2015-10-28 | 南京理工大学 | Preparation method of PDMS microfluidic chip based on liquid composite molding method |
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