CN108636464A - A kind of drop micro-fluidic chip, molding machine and preparation method thereof - Google Patents
A kind of drop micro-fluidic chip, molding machine and preparation method thereof Download PDFInfo
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- CN108636464A CN108636464A CN201810284866.8A CN201810284866A CN108636464A CN 108636464 A CN108636464 A CN 108636464A CN 201810284866 A CN201810284866 A CN 201810284866A CN 108636464 A CN108636464 A CN 108636464A
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- 238000000465 moulding Methods 0.000 title claims abstract description 101
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 239000000565 sealant Substances 0.000 claims abstract description 38
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 43
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 43
- 238000007493 shaping process Methods 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 24
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- 239000010426 asphalt Substances 0.000 claims description 4
- 230000007717 exclusion Effects 0.000 claims description 4
- 239000003566 sealing material Substances 0.000 claims description 4
- NJPPVKZQTLUDBO-UHFFFAOYSA-N novaluron Chemical compound C1=C(Cl)C(OC(F)(F)C(OC(F)(F)F)F)=CC=C1NC(=O)NC(=O)C1=C(F)C=CC=C1F NJPPVKZQTLUDBO-UHFFFAOYSA-N 0.000 claims description 2
- 239000002861 polymer material Substances 0.000 claims description 2
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims 6
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 claims 6
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- 238000004519 manufacturing process Methods 0.000 description 9
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- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
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Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- 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
- B01L3/502707—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 characterised by the manufacture of the container or its components
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Dispersion Chemistry (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Micromachines (AREA)
Abstract
The present invention provides a kind of drop micro-fluidic chip, molding machine and preparation method thereof, drop micro-fluidic chip includes：Bottom plate, flow channel layer, supporting layer and sealant, flow channel layer are stacked in the top of bottom plate, and the bottom surface of flow channel layer is equipped with the runner for being used to form drop, and bottom plate seals runner, and the top surface of flow channel layer is equipped with multiple connecting poles；Supporting layer, is stacked in the top of flow channel layer, and supporting layer has the connecting hole worn for connecting pole；Sealant, is stacked in the top of supporting layer, technical solution of the present invention overcome in the prior art drop micro-fluidic chip need to be driven using syringe pump, it is more demanding to the bond strength of chip；Chip needs the problem of being connected with external fluid path and connector, operation is not easy to when adding sample and reagent.
Description
Technical field
The present invention relates to microfluidic arts, and in particular to a kind of drop micro-fluidic chip, molding machine and its preparation
Method.
Background technology
Drop microflow control technique is different from traditional continuous flow microfluidic system, and drop microflow control technique is using immiscible
Two-phase fluid formed microlayer model, the drop of dispersion is manipulated, is a kind of discontinuous flow microflow control technique.
Drop microflow control technique has various features：Between drop independently of each other, no cross contamination and diffusion；It is small,
The dosage of sample and reagent is few；Surface area is big, and heat transfer speed is fast；Generating rate is fast, and flux is high；Drop size is uniform, single point
It is good to dissipate property.Since technical characterstic protrudes, drop microflow control technique is widely used in functional material synthesis, life science and food
Product processing and other fields.
Currently, most common drop formation method is driven using syringe pump, have the following disadvantages：
1, drop micro-fluidic chip needs are connect with external equipment and pipe joint, and integrated level is low, and device is complicated, is not easy to
Operation.Due to needing to transport sample and reagent by exterior line and connector, needed in actual mechanical process a large amount of sample and
Reagent, and there are dead volumes for pipe fitting, be easy to cause the loss of sample and reagent；It is difficult to operate again when sample size is less.
2, syringe pump is to drive liquid by way of providing positive pressure driving force, to the bond strength of chip require compared with
Height, such type of drive pressure are easy to cause chip leakage when excessive.And conventional syringe pump drives liquid using stepper motor
Body, there are pulse effects, it is difficult to which the flow velocity and pressure of liquid with precise control, this can influence the stability of flow rate of liquid, reduce liquid
Drip the homogeneity of size.Pressure-driven pumps that the response time is short, and stability is high, can be used to substitute syringe pump, but its price
Costliness, which has limited its application ranges.
Therefore, one kind is now needed to be operated when adding sample and reagent more convenient, and to chip bonding intensity requirement
Lower drop micro-fluidic chip realizes the accurate manipulation of drop preparation process while ensureing droplet uniformity.
Invention content
The main purpose of the present invention is to provide a kind of drop micro-fluidic chips, molding machine and preparation method thereof, with solution
Certainly drop micro-fluidic chip need to be driven using syringe pump in the prior art, more demanding to the bond strength of chip；Chip
The problem of needing to be connected with external fluid path and connector, operation is not easy to when adding sample and reagent.
To achieve the above object, the present invention provides a kind of drop micro-fluidic chips, including：Bottom plate, flow channel layer, supporting layer
And sealant, flow channel layer, it is stacked in the top of bottom plate, the bottom surface of flow channel layer is equipped with the runner for being used to form drop, and bottom plate is close
Runner is sealed, the top surface of flow channel layer is equipped with multiple connecting poles；Supporting layer, is stacked in the top of flow channel layer, and supporting layer has for even
Connect the connecting hole that column is worn；Sealant is stacked in the top of supporting layer；Wherein, on sealant, part connecting pole and flow channel layer
Corresponding position is equipped with sample cavity, oil pocket and drop collecting chamber, corresponding sample between sealant, part connecting pole and flow channel layer
Chamber, oil pocket and drop collecting chamber are interconnected, and sealant, part connecting pole and flow channel layer on flow channel layer are connected to runner,
The connecting pole connection sealant and flow channel layer of remaining part point.
Further, the relationship of the thickness Ht of the height h and flow channel layer of runner is：10 × h≤Ht≤100 × h, and/or,
The relationship of the height h of runner and the thickness Hb of bottom plate is：10×h≤Hb≤50×h.
Further, the volume Vd of drop collecting chamber is equal to the sum of the volume Vs of the volume Vo and sample cavity of oil pocket.
Further, the diameter and quantity for the connecting hole that the connecting pole of rest part is worn are respectively D and N, supporting layer
Area is S, wherein 2S/25 π D2≤N≤S/2πD2, D is 1~10mm.
Further, runner includes asphalt channel, the sample of connection corresponding with oil pocket, sample cavity and drop collecting chamber respectively
Channel and drop channel.
Further, drop micro-fluidic chip further includes being stacked in the top of supporting layer and being centered around enclosing for sealant surrounding
Column, fence and supporting layer are integrally formed or seperated molding.
Further, sealant, multiple connecting poles, flow channel layer form the first flexible chip, and fence and supporting layer are formed firmly
Matter chip, bottom plate form the second flexible chip, mold the first flexible chip by method of molding in hard cores on piece, second is flexible
Chip is molded also by method of molding.
Further, sealant, connecting pole, flow channel layer and bottom plate are PDMS material.
Further, supporting layer and fence are stiff polymer material.
Further, the thickness of flow channel layer is 0.5~5mm.
Further, the thickness of bottom plate is 0.5~10mm.
Further, the thickness of supporting layer is 1~10mm.
Further, the thickness of fence and sealant is 0.5~5mm.
The present invention also provides a kind of molding machines of molding drop micro-fluidic chip, including：Runner molding machine and bottom
Plate forming device, runner molding machine include：First base, mold, the first profiled sheeting, fixed plate and multiple shaping columns, first
Pedestal, first base have first to place groove；Mold is placed in the first placement groove, and the surface of mold, which is equipped with, to be used for
Generate the molding structure of runner；First profiled sheeting is stacked in the top of first base, and the first profiled sheeting has placed cavity, places
Intracavitary places supporting layer；Fixed plate is arranged on the first profiled sheeting and has multiple mounting holes；Multiple shaping columns, multiple moldings
Column is each passed through corresponding mounting hole and is inserted into the part connecting hole on supporting layer, and the diameter D2 of shaping column is less than corresponding connection
The diameter D1 in hole, mold, the first profiled sheeting, supporting layer and shaping column form forming cavity.
Further, the diameter D1 of the diameter D2 of each shaping column and corresponding each connecting hole, meets following relationship：
1.2×D2≤D1≤2×D2。
Further, first base is equipped with the first mounting hole, and the first profiled sheeting is equipped with the second mounting hole, runner molding
Device further includes the first connector, and the first connector passes through from the second mounting hole and is fixed on the first mounting hole；In first base
Equipped with first positioning hole, the first profiled sheeting is equipped with second location hole, and fixed plate is equipped with third location hole, runner molding machine
Further include locating piece, locating piece is passed through from third location hole, second location hole successively to be coordinated with first positioning hole afterwards.
Further, baseplate molding device includes：Second base, molding egative film, the second profiled sheeting and the second connector, the
Two pedestals have second to place groove；It is molded egative film, is placed in the second placement groove, the surfacing for being molded egative film is smooth；
Second profiled sheeting is stacked in the top of molding egative film and with the forming through hole for corresponding to molding egative film；Second connector, second
Profiled sheeting is connected with second base by the second connector.
The preparation method of drop micro-fluidic chip is prepared using molding machine the present invention also provides a kind of, including is walked as follows
Suddenly：Mold is placed in the first placement groove, the first profiled sheeting is stacked in first base, by sealing material by mold with
It is sealed between first profiled sheeting, supporting layer is placed in placed cavity, pass through sealing between supporting layer and the first profiled sheeting
Material seals, and fixed plate is placed on the first profiled sheeting, shaping column is inserted into mounting hole；By certain mass than preparing
PDMS after being sufficiently stirred, vacuumizes exclusion bubble, and liquid PDMS is poured slowly by the connecting hole in forming cavity, stands
Be heating and curing molding after PDMS Self-levelings；Fixed plate, shaping column are removed successively, and the part after solidification is taken from placed cavity
Go out, completes demoulding；Face to be bonded is handled to part and bottom plate, is bonded rapidly after processing, airtight passage is formed.
Further, baseplate molding device includes：Second base has second to place groove；It is molded egative film, is placed on the
Two place in groove, and the surfacing for being molded egative film is smooth；Second profiled sheeting is stacked in the top of molding egative film and with correspondence
Further include following steps before to bottom plate processing face to be bonded in the forming through hole of molding egative film：Molding egative film is placed on
The second of second base is placed in groove, and the second profiled sheeting is stacked in second base, liquid PDMS is poured into the second molding
In the forming through hole of plate, the molding that is heating and curing after PDMS Self-levelings is stood；Bottom plate is taken out from forming through hole, is completed de-
Mould.
Technical solution of the present invention has the following advantages that：When generating drop using this drop micro-fluidic chip, will directly it bear
Crimp head is connected with drop collecting chamber, and using negative-pressure cup as negative pressure source, driving two-phase fluid forms microlayer model, pressure response
Time is short, and liquid flowing is more stablized, and the consistency of drop is more preferable；The requirement to chip bonding intensity, cost are reduced simultaneously
It is low, generate the mode of operation of drop also fairly simple convenience；And the chip need not be connected directly with external fluid path and connector,
Sample and reagent can be added by pipettor, the loss of sample and reagent will not be caused, also not by the volume of sample and reagent
Size influences, and adds sample and reagent is more convenient.Negative pressure may be used in the drop micro-fluidic chip of the present invention or positive pressure carries out
Driving, preferably negative pressure drive.
The material of this drop micro-fluidic chip includes silicon rubber PDMS and transparent polymer plate, wherein PDMS
(Polydimethylsiloxane, dimethyl silicone polymer) is a kind of flexible macromolecule polymer, and transparent polymer plate is
The rigid polymers such as PMMA, PC, PP, PS, ABS.PDMS material is soft, and elasticity is good, it is easy to accomplish fluid channel it is molded；Draw
Enter rigid polymer, the hardness of drop micro-fluidic chip entirety can be improved, convenient for connection pressure source.By flexible material and hard
Material is combined, and is learnt from other's strong points to offset one's weaknesses, and forms flexibility+hard drop micro-fluidic chip, manufacture craft is simple, at low cost.
Description of the drawings
It, below will be to specific in order to illustrate more clearly of the specific embodiment of the invention or technical solution in the prior art
Embodiment or attached drawing needed to be used in the description of the prior art are briefly described, it should be apparent that, in being described below
Attached drawing is some embodiments of the present invention, for those of ordinary skill in the art, before not making the creative labor
It puts, other drawings may also be obtained based on these drawings.In the accompanying drawings：
Fig. 1 shows the overall structure signal of the drop micro-fluidic chip provided in the first embodiment of the invention
Figure；
Fig. 2 shows the decomposition texture schematic diagrams of the drop micro-fluidic chip of Fig. 1；
Fig. 3 shows the vertical view of the drop micro-fluidic chip of Fig. 1；
Fig. 4 shows the drop micro-fluidic chip of Fig. 3 details enlarged drawing along the sectional view and A of A-A hatching lines；
Fig. 5 shows the sectional view along B-B hatching lines of the drop micro-fluidic chip of Fig. 3；
Fig. 6 shows the overall structure diagram of the runner molding machine of molding machine according to the present invention；
Fig. 7 shows the decomposition texture schematic diagram of the runner molding machine of Fig. 6；
Fig. 8 shows the vertical view of the runner molding machine of Fig. 6；
Fig. 9 shows the sectional view of the runner molding machine cast forward position C-C hatching lines of Fig. 6；
Figure 10 show Fig. 6 runner molding machine cast after along C-C hatching lines sectional view；
Figure 11 shows the sectional view of the part after the runner molding machine demoulding of Figure 10；
Figure 12 shows the overall structure diagram of the baseplate molding device of molding machine according to the present invention；
Figure 13 shows the decomposition texture schematic diagram of the baseplate molding device of Figure 12；
Figure 14 shows the stereogram of the four-way drop micro-fluidic chip provided in second of embodiment of the invention
And vertical view；
Figure 15 shows the stereogram of the eight channel drop micro-fluidic chips provided in the third embodiment of the invention
And vertical view；
Figure 16 shows the stereogram of the axial symmetry drop micro-fluidic chip provided in the 4th kind of embodiment of the invention
And vertical view；
Figure 17 shows the eight channel axial symmetry drop micro-fluidic chips provided in the 5th kind of embodiment of the present invention
Stereogram and vertical view；
Figure 18 shows the solid of the central symmetry drop micro-fluidic chip provided in the 6th kind of embodiment of the invention
Figure and vertical view.
Wherein, the reference numeral in above-mentioned attached drawing is：
10, bottom plate；20, flow channel layer；21, connecting pole；211, sample cavity；212, oil pocket；213, drop collecting chamber；22, it flows
Road；221, asphalt channel；222, sample channel；223, drop channel；30, supporting layer；31, connecting hole；32, fence；40, it seals
Layer；50, first base；51, the first mounting hole；52, first positioning hole；53, first groove is placed；60, mold；70, the first one-tenth
Template；71, placed cavity；711, chamfering；72, the second mounting hole；73, second location hole；80, fixed plate；81, mounting hole；82,
Three location holes；90, shaping column；100, the first connector；110, locating piece；120, second base；121, second groove is placed；
122, it is molded egative film；140, the second profiled sheeting；141, forming through hole；150, the second connector.
Specific implementation mode
Technical scheme of the present invention is clearly and completely described below in conjunction with attached drawing, it is clear that described implementation
Example is a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, ordinary skill
The every other embodiment that personnel are obtained without making creative work, shall fall within the protection scope of the present invention.
Embodiment 1
As shown in Figures 1 to 5, the present invention provides a kind of drop micro-fluidic chips, including：Bottom plate 10, flow channel layer 20, branch
Layer 30 and sealant 40 are supportted, flow channel layer 20 is stacked in the top of bottom plate 10, and the bottom surface of flow channel layer 20, which is equipped with, is used to form drop
Runner 22, bottom plate 10 seals runner, and the top surface of flow channel layer 20 is equipped with multiple connecting poles 21；Supporting layer 30 is stacked in flow channel layer
20 top, supporting layer 30 have the connecting hole 31 worn for connecting pole 21；Sealant 40 is stacked in the top of supporting layer 30；Its
In, the corresponding position on sealant 40, part connecting pole 21 and flow channel layer 20 is equipped with sample cavity 211, oil pocket 212 and drop and receives
Collect chamber 213, corresponding sample cavity 211, oil pocket 212 and drop are collected between sealant 40, part connecting pole 21 and flow channel layer 20
Chamber 213 is interconnected, and sealant 40, part connecting pole 21 and flow channel layer 20 on flow channel layer 20 are connected to runner 22, remaining part
The connecting pole 21 divided connects sealant 40 and flow channel layer 20.
When generating drop using this drop micro-fluidic chip, directly negative pressure connector is connected with drop collecting chamber 213,
Using negative-pressure cup as negative pressure source, driving two-phase fluid forms microlayer model, and pressure response time is short, and liquid flowing is more stablized,
The consistency of drop is more preferable；The requirement to chip bonding intensity is reduced simultaneously, and at low cost, the mode of operation for generating drop also compares
It is more simple and convenient；And the chip need not be connected directly with external fluid path and connector, can by pipettor add sample and
Reagent will not cause the loss of sample and reagent, also not influenced by the volume size of sample and reagent, add sample and reagent compared with
For convenience.Negative pressure may be used for the drop micro-fluidic chip of the present invention or positive pressure is driven, and preferably negative pressure drives.
The material of this drop micro-fluidic chip includes silicon rubber PDMS and transparent polymer plate, wherein PDMS
(Polydimethylsiloxane, dimethyl silicone polymer) is a kind of flexible macromolecule polymer, and transparent polymer plate is
The rigid polymers such as PMMA, PC, PP, PS, ABS.PDMS material is soft, and elasticity is good, it is easy to accomplish fluid channel it is molded；Draw
Enter rigid polymer, the hardness of drop micro-fluidic chip entirety can be improved, convenient for connection pressure source.By flexible material and hard
Material is combined, and is learnt from other's strong points to offset one's weaknesses, and forms flexibility+hard drop micro-fluidic chip, manufacture craft is simple, at low cost.
In the production process, so that supporting layer 30 is integrally formed with flow channel layer 20 equal by method of molding, be formed simultaneously sample
Chamber 211, oil pocket 212 and drop collecting chamber 213, therefore this drop micro-fluidic chip is not only simple in structure, and manufacturing process
Also relatively easy.
Specifically, the relationship of the thickness Ht of the height h and flow channel layer 20 of runner 22 is：10 × h≤Ht≤100 × h, runner
Height h and the relationship of the thickness Hb of bottom plate 10 be：10×h≤Hb≤50×h.Flow channel layer 20 is fixed on branch by connecting pole 21
It supportting on layer 30, flow channel layer 20 needs to meet certain thickness and hardness, when the two ratio is smaller, i.e., when Ht is smaller, flow channel layer 20
Hardness is insufficient, is easy to split away off from supporting layer 30 during demoulding, therefore, it is necessary to the thickness by increasing flow channel layer 20
Ht improves its hardness.The height h of runner is generally tens microns to 100 microns, from the experimental result of the following table 1 it is found that
Convenient for demoulding when Ht=10h, Ht is bigger, and required PDMS is more, considers cost of manufacture, selects following 10 × h of range≤Ht
≤100×h；10 thickness of bottom plate is excessively thin, and bottom plate 10, which is easily deformed, in operation even ruptures, and is not easy to be bonded, from the following table 2
The experimental results showed that, convenient for picking and placeing and being bonded when Hb=10h, hardness and strength are more suitable, and the thickness Hb of bottom plate 10 is got over
Greatly, required PDMS is more, considers cost of manufacture, selects following range：10×h≤Hb≤50×h.
Table 1
Table 2
Specifically, the volume Vd of drop collecting chamber 213 be equal to volume Vo and the sample cavity 211 of oil pocket 212 volume Vs it
With.Since the liquid in oil pocket 212 and sample cavity 211 eventually flows to drop collecting chamber 213, triadic relation should meet Vo+
Vs=Vd.
Specifically, the volume of oil pocket 212, sample cavity 211 and drop collecting chamber 213 is 1-5 times of respective liquid volume, excellent
Select 1.5-3 times.By the experimental result of the following table 3 it is found that ensure that liquid does not overflow, the volume ratio of the two is at least 1.5：1, it examines
Consider cost of manufacture and chip free space, the two ratio cannot be more than 3:1.
Table 3
| The ratio of chamber volume and liquid volume | Whether it is easy to overflow (Y/N) |
| 1:1 | Y |
| 1.2:1 | Y |
| 1.3:1 | Y |
| 1.4: | Y |
| 1.5:1 | N |
Specifically, the diameter and quantity for the connecting hole 31 that the connecting pole 21 of rest part is worn are respectively D and N, supporting layer
30 area is S, wherein 2S/25 π D2≤N≤S/2πD2, D is 1~10mm.The effect of connecting hole 31 is connection 40 He of sealant
Flow channel layer 20,31 quantity of connecting hole is very few, and connection effect is poor, and flow channel layer 20 is easy to fall off；31 quantity of connecting hole is excessive, although protecting
Connection effect has been demonstrate,proved, but the intensity of supporting layer 30 can be caused to reduce, the deformation of supporting layer 30 has been be easy to cause, is sealed when generating drop
The sealing effect of layer 40 can reduce, and gas leakage is easy, and supporting layer 30 is easily broken off, from the test result of the following table 4：Connection
The area relationship of 31 quantity of hole and supporting layer 30 is 1:50≤NπD2/(4S)≤1:When 8, both 2S/25 π D2≤N≤S/2πD2When,
Flow channel layer 20 is least easy to fall off with connecting pole 21 and the intensity of supporting layer 30 can meet the requirement needed for drop formation.
Table 4
Specifically, connecting hole 31 can be round, rectangular, triangle, diamond shape etc., circular, and 31 diameter D of connecting hole is
1-10mm, preferably 2-3mm, connecting hole 31 can also carry internal thread, facilitate fixed connection and sealing layer 40 and flow channel layer 20.
Specifically, the diameter of connecting pole 21 and height are determined by the diameter and height of connecting hole 31.Since connecting pole 21 is
It is poured into a mould and to be formed by method of molding, therefore the size of connecting hole 31 determines the size of connecting pole 21.Connecting pole 21 is used for will be close
Sealing 40 and flow channel layer 20 are fixed on supporting layer 30.
Specifically, runner includes that the oil circuit of connection corresponding with oil pocket 212, sample cavity 211 and drop collecting chamber 213 respectively is logical
Road 221, sample channel 222 and drop channel 223.Drop is generated using flow focusing method, by negative pressure driven devices and collecting chamber
It is connected, under the action of negative pressure driving force, the dispersion sample in sample channel 222 is by the continuous phase of both sides asphalt channel 221
Oil shearing forms drop.Runner is PDMS material, is convenient for surface modification.
Specifically, drop micro-fluidic chip further includes being stacked in the top of supporting layer 30 and being centered around 40 surrounding of sealant
Fence 32, fence 32 and supporting layer 30 are integrally formed or seperated molding.During pouring into a mould part using method of molding, fence 32
Thickness for determining sealant 40, fence 32 are metal or rigid polymer plate, preferably rigid polymer plate, supporting layer 30
It is convenient that drop formation process is observed in real time for clear hard polymer sheet, hard transparent polymer sheet be PMMA, PC,
PP, PS, ABS etc., hard transparent polymer sheet may be reused, and metal is aluminium alloy, stainless steel etc..
Specifically, sealant 40, multiple connecting poles 21, flow channel layer 20 form the first flexible chip, fence 32 and supporting layer
30 form hard chip, and bottom plate 10 forms the second flexible chip, the first flexible core is molded by method of molding in hard cores on piece
Piece, the second flexible chip are molded also by method of molding.
Specifically, sealant 40, multiple connecting poles 21, flow channel layer 20 and bottom plate 10 are flexible PDMS material.Using phase
Same material reduces the difficulty of chip sealing bonding, convenient for being subsequently modified processing, and PDMS and rigid polymer plate
It is transparent material, convenient for being observed in real time drop formation process.
Specifically, the thickness of flow channel layer 20 is 0.5~5mm, preferably 1-3mm.Can meet thickness and hardness requirement and
The requirement of cost can be met, therefore select this range.
Specifically, 10 thickness of bottom plate is 0.5~10mm, and preferably 1-3mm, for bottom plate 10 for sealing runner, formation is closed logical
Road, 10 thickness of bottom plate is excessively thin, is easily deformed in the operating process bottom plate 10 for generating drop and even ruptures, is not easy to be bonded, bottom
10 thickness of plate is blocked up so that cost of manufacture is got higher, therefore selects this range,
Specifically, the thickness of supporting layer 30 is 1~10mm.Supporting layer 30 is used to provide hard branch to sealant 40 and runner
Fixed chip is convenient in support, realizes that chip is connected and detached with the quick of negative pressure system.The intensity of supporting layer 30 needs to meet drop
Formation condition, it is not easy to break, and in view of cost requirement selects this range.
Specifically, the thickness of fence 32 and sealant 40 is 0.5~5mm, the thickness of sealant 40 by fence 32 height
Degree determines.Sealant 40 is used for during drop formation, realizes the sealing between micro-fluidic chip and negative pressure system, Jin Erbao
Hold pressure stability.
As shown in Fig. 6, Fig. 7, Fig. 8 and Figure 12, the present invention also provides a kind of moldings of the above-mentioned drop micro-fluidic chip of molding
Device, including：Runner molding machine and baseplate molding device, runner molding machine include：First base 50, mold 60, first
Profiled sheeting 70, fixed plate 80 and multiple shaping columns 90, first base 50 have first to place groove 53；Mold 60 is placed on first
It places in groove 53, the surface of mold 60 is equipped with the structure for generating runner；First profiled sheeting 70 is stacked in first base
50 top, the first profiled sheeting 70 have placed cavity 71, supporting layer 30 are placed in placed cavity 71；Fixed plate 80 is placed on the first one-tenth
On template 70 and there are multiple mounting holes 81；Multiple shaping columns 90 are each passed through corresponding mounting hole 81 and are inserted on supporting layer 30
In part connecting hole 31, the diameter D2 of shaping column 90 is less than the diameter D1 of corresponding connecting hole 31, mold 60, the first profiled sheeting
70, supporting layer 30 and shaping column 90 form forming cavity.
Runner molding machine is used to make flow channel layer 20, connecting pole 21, sample cavity 211, the oil pocket of drop micro-fluidic chip
212, drop collecting chamber 213 and sealant 40, above structure are an integral molding structure with 30 structure of supporting layer, realize seamless company
It connects.Shaping column 90 is used to form sample cavity 211, oil pocket 212, drop collecting chamber 213, therefore the outer diameter of shaping column 90 is corresponding cavity
The internal diameter of room.It can be facilitated using runner molding machine and make drop micro-fluidic chip, it is easy to operate；Baseplate molding device is used for
10 structure of bottom plate is made, manufacturing process is simple and convenient.
Specifically, first base 50, the first profiled sheeting 70, fixed plate 80 material be polymer or metal, preferred metal,
It can ensure their hardness.
Specifically, the material of shaping column 90 is polymer or metal, preferred polymers, such as fluoroplastics.
Specifically, the material of mold 60 is silicon chip, metal, glass or polymer, preferably silicon chip.
Specifically, the diameter D1 of the diameter D2 of each shaping column 90 and corresponding each connecting hole 31 meets such as ShiShimonoseki
System：1.2×D2≤D1≤2×D2.Shaping column 90 and connecting hole 31 are connected for making sample cavity, oil pocket and drop collecting chamber
Bore dia is more than molding column diameter, after cast so that and being formed between shaping column and connecting hole has certain thickness PDMS layer,
This PDMS layer forms connecting pole, and sealant is connected by PDMS layer with flow channel layer after demoulding, such three chambers and flow channel layer
It is finally all wrapped up by same material PDMS, chamber inner wall does not have any leakage point.In addition, connection bore dia be more than at
Type column diameter, convenient for extracting shaping column in knockout course, PDMS layer needs to meet certain thickness, when extracting shaping column in this way
PDMS layer is not easy to break.
Specifically, first base 50 is equipped with the first mounting hole 51, and the first profiled sheeting 70 is equipped with the second mounting hole 72, stream
Road molding machine further includes the first connector 100, and the first connector 100 passes through from the second mounting hole 72 and is fixed on the first fixation
Hole 51；First base 50 is equipped with first positioning hole 52, and the first profiled sheeting 70 is equipped with second location hole 73, is set in fixed plate 80
It further includes locating piece 110 to have third location hole 82, runner molding machine, and locating piece 110 is fixed from third location hole 82, second successively
Position hole 73 passes through to be coordinated with first positioning hole 52 afterwards.Preferably, the first connector 100 is screw, and locating piece 110 is pin.
Specifically, first base 50 is surrounded by least one step structure, in order to separated first base 50 and
One profiled sheeting 70.Straight flange or right angle in first base 50 is arranged in step structure, and step structure can be triangle, square
Shape, semicircle or any facilitate the separated structure of first base 50 and the first profiled sheeting 70, the step of first base 50
The height of structure is 0.2-5mm, preferably 2-3mm.
As shown in fig. 7, specifically, the inner ring four corners of placed cavity 71 are provided with chamfering 711, and 711 one side of chamfering is convenient for
Drop micro-fluidic chip is taken out from placed cavity 71 when demoulding；On the other hand, prevent cast when PDMS from placed cavity 71
It overflows, chamfering 711 is 30-80 degree, preferably 45-60 degree.
The specific assemble method of runner molding machine is as follows：First between the first profiled sheeting of silicone grease pair 70 and mold 60
It is sealed, in order to prevent liquid PDMS in casting process from generating leakage, and be sealed convenient for more using silicone grease
Mold exchange 60 has placed silicon mould 60, the first profiled sheeting 70 and first base 50 and has carried out positioning by pin and consolidated by screw
It is fixed, the supporting layer 30 for being fixed with fence 32 is put into placed cavity 71, to prevent in casting process PDMS from 30 bottom of supporting layer
Portion lets out, using silicone grease or double faced adhesive tape sealing placed cavity 71 and supporting layer 30.Fixed plate 80 is placed in the first profiled sheeting
70 top, fixed plate 80, the first profiled sheeting 70 and 50 three of first base are positioned by pin, finally by shaping column 90
It is inserted into mounting hole 81.So far, runner molding machine completes assembling.
As shown in Figure 12 and Figure 13, specifically, baseplate molding device includes：Second base 120, molding egative film 122, second
Profiled sheeting 140 and the second connector 150, second base 120 have second to place groove 121；It is molded egative film 122, is placed on the
Two place in groove 121, and the surfacing for being molded egative film 122 is smooth；Second profiled sheeting 140 is stacked in the upper of molding egative film 122
Side simultaneously has the forming through hole 141 for corresponding to molding egative film 122；Second connector 150, the second profiled sheeting 140 and second base
120 are connected by the second connector 150.
Specifically, the surrounding of second base 120 is provided at least one step structure, in order to separated second base 120
With second profiled sheeting 140.
The specific assemble method of baseplate molding device is as follows：It is that silicon chip is placed on the second placement groove by molding egative film 122
In 121, using silicone grease, double faced adhesive tape or epoxy glue sealing silicon chip and the second profiled sheeting 140, preferably epoxy glue, silicon chip can
To ensure to obtain the smooth bottom plate 10 of surfacing, recycle screw that second base 120 and the second profiled sheeting 140 are fixed on one
It rises, so far completes the assembling to baseplate molding device.
The present invention also provides a kind of preparation method preparing drop micro-fluidic chip using above-mentioned molding machine, including it is as follows
Step：
Mold 60 is placed in the first placement groove 53, the first profiled sheeting 70 is stacked in first base 50, by close
Closure material will be sealed between mold 60 and the first profiled sheeting 70, supporting layer 30 is placed in placed cavity 71, supporting layer 30
It is sealed by sealing material between the first profiled sheeting 70, fixed plate 80 is placed on the first profiled sheeting 70, by shaping column 90
It is inserted into mounting hole 81；
By certain mass than preparing PDMS, after being sufficiently stirred, exclusion bubble is vacuumized, liquid PDMS is passed through into the connection
Hole 31 is poured slowly into forming cavity, stands the molding that is heating and curing after PDMS Self-levelings；
Fixed plate 80, shaping column 90 are removed successively, the part after solidification is taken out from placed cavity 71, complete demoulding；
Face to be bonded is handled to part and bottom plate 10, is bonded rapidly after processing, airtight passage is formed.
Specifically, baseplate molding device includes：Second base 120 has second to place groove 121；It is molded egative film 122,
It is placed in the second placement groove 121, the surfacing for being molded egative film 122 is smooth；Second profiled sheeting 140, is stacked in formed sole
The top of piece 122 simultaneously has the forming through hole 141 for corresponding to molding egative film 122, before handling face to be bonded to bottom plate 10 also
Include the following steps：Egative film 122 will be molded to be placed in the second placement groove 121 of second base 120, by the second profiled sheeting
140 are stacked in second base 120, liquid PDMS are poured into the forming through hole 141 of the second profiled sheeting 140, and standing waits for PDMS
Be heating and curing molding after Self-leveling；Bottom plate 10 is taken out from forming through hole 141, completes demoulding.
Specifically, further include following steps after forming airtight passage：Hydrophobic treatment is carried out to airtight passage, after processing
Purge airtight passage.
Specifically, hydrophobic treatment includes the following steps：Oil pocket 212 and sample cavity 211, infiltration one is added in surfactant
After the section time, negative pressure is applied to drop collecting chamber, the surfactant in oil pocket 212 and sample cavity 211 is discharged.
In conjunction with Fig. 9, Figure 10 and Figure 11, the preparation method of drop micro-fluidic chip is described in detail：
Assemble runner molding machine and baseplate molding device；
By certain mass than preparing PDMS, after being sufficiently stirred, exclusion bubble is vacuumized；
Liquid PDMS is poured slowly by the connecting hole 31 of supporting layer 30 in the placed cavity 71 of the first profiled sheeting 70, is stood
Wait for PDMS Self-levelings；Liquid PDMS is poured into the forming through hole 141 of the second profiled sheeting 140, standing waits for PDMS Self-levelings；
Runner molding machine and baseplate molding device are put into baking oven or hot plate and heated, curing molding, the solidification of PDMS
Temperature should be less than the softening point of hard transparent polymer；
Pin, fixed plate 80, shaping column 90 are removed successively, the part after solidification are taken out out of placed cavity 71, by bottom plate
10 take out out of second profiled sheeting 140, complete demoulding；
The part for completing cast and bottom plate are put into oxygen plasma treatment equipment, key is waited for using oxygen plasma treatment
Conjunction face；
Part and 10 plate of bottom plate are taken out, it is rapid to be bonded, form airtight passage；
Hydrophobic treatment is carried out to airtight passage using liquid phase method of modifying, oil pocket 212 and sample is added in surfactant
Chamber 211, activating agent quickly fill with runner under the action of capillary force.After infiltrating a period of time, apply negative pressure in drop collecting chamber,
The activating agent in oil pocket 212 and sample cavity 211 is discharged；
Nitrogen purges runner, and remaining activating agent in runner is further discharged.
Described above is how to make single channel drop micro-fluidic chip, in practical applications to improve flux, is needed
It realizes multiple sample parallel generation drops, multichannel drop micro-fluidic chip can be prepared using identical method.
Embodiment 2
As shown in figure 14, it is on the basis of embodiment 1 the present embodiment provides a kind of four-way drop micro-fluidic chip
Deformation, difference lies in four groups of structures for generating drop.The present embodiment can make multiple sample parallel generation drops, into
And improve flux.
Embodiment 3
As shown in figure 15, it is on the basis of embodiment 1 the present embodiment provides a kind of eight channel drop micro-fluidic chips
Deformation, difference lies in eight groups of structures for generating drop.The present embodiment can make multiple sample parallel generation drops, into
And improve flux.
Embodiment 4
As shown in figure 16, it is on the basis of embodiment 1 the present embodiment provides a kind of axial symmetry drop micro-fluidic chip
Deformation, difference lies in tools there are one collecting chamber, and collecting chamber both sides structure is symmetrical, and the both sides of collecting chamber are all provided with that there are one oil pockets
212 and a sample cavity 211.Single channel drop micro-fluidic chip is subjected to array to get to the axial symmetry miniflow of the present embodiment
Chip is controlled, the drop that two groups of chip generates can be converged in the same drop collecting chamber, made by this drop micro-fluidic chip
It obtains drop formation rate and promotes one times, to realize that high speed mass generates the function of drop.
Embodiment 5
As shown in figure 17, it is in 4 base of embodiment the present embodiment provides a kind of eight channel axial symmetry drop micro-fluidic chips
Deformation on plinth, difference lies in eight collecting chambers, and the straight line being linked to be using the center of circle of each collecting chamber is symmetry axis, symmetrically
Axis both sides structure is symmetrical, and the both sides of each collecting chamber are all provided with that there are one oil pocket 212 and a sample cavities 211.Pass through array
Axial symmetry drop micro-fluidic chip can obtain the drop micro-fluidic chip of the present embodiment, and this drop micro-fluidic chip not only may be used
To improve drop formation rate, but also can meet the needs of multiple sample parallel generation drops.
Embodiment 6
As shown in figure 18, it is on the basis of embodiment 1 the present embodiment provides a kind of central symmetry drop micro-fluidic chip
Deformation, difference lies in tools there are one collecting chamber, and several 212 Hes of oil pocket are arranged by symmetric points of the center of circle of this collecting chamber
Sample cavity 211 so that symmetric figure centered on the vertical view of drop micro-fluidic chip.The drop micro-fluidic chip of the present embodiment will
The drop that eight channel designs generate converges in a collecting chamber, improves drop formation rate, to realize high speed batch
Amount generates the function of drop.
Obviously, the above embodiments are merely examples for clarifying the description, and does not limit the embodiments.It is right
For those of ordinary skill in the art, can also make on the basis of the above description it is other it is various forms of variation or
It changes.There is no necessity and possibility to exhaust all the enbodiments.And it is extended from this it is obvious variation or
It changes still within the protection scope of the invention.
Claims (15)
1. a kind of drop micro-fluidic chip, which is characterized in that including：
Bottom plate (10)；
Flow channel layer (20) is stacked in the top of the bottom plate (10), and the bottom surface of the flow channel layer (20), which is equipped with, is used to form liquid
The runner (22) of drop, the bottom plate (10) seal the runner (22), and the top surface of the flow channel layer (20) is equipped with multiple connections
Column (21)；
Supporting layer (30), is stacked in the top of the flow channel layer (20), and the supporting layer (30) has for the connecting pole (21)
The connecting hole (31) worn；
Sealant (40), is stacked in the top of the supporting layer (30)；
Wherein, the corresponding position on the sealant (40), the part connecting pole (21) and the flow channel layer (20) is equipped with
Sample cavity (211), oil pocket (212) and drop collecting chamber (213), the sealant (40), the part connecting pole (21) and institute
The corresponding sample cavity (211), the oil pocket (212) and the drop collecting chamber (213) are mutual between stating flow channel layer (20)
It is connected to, the sealant (40), the part connecting pole (21) and the flow channel layer (20) on the flow channel layer (20) and institute
Runner (22) connection is stated, the connecting pole (21) of rest part connects the sealant (40) and the flow channel layer (20).
2. drop micro-fluidic chip according to claim 1, which is characterized in that the height h of the runner (22) with it is described
The relationship of the thickness Ht of flow channel layer (20) is：10 × h≤Ht≤100 × h, and/or, the height h of the runner (22) with it is described
The relationship of the thickness Hb of bottom plate (10) is：10×h≤Hb≤50×h.
3. drop micro-fluidic chip according to claim 1, which is characterized in that the volume of the drop collecting chamber (213)
Vd is equal to the sum of the volume Vs of the volume Vo and the sample cavity (211) of the oil pocket (212).
4. drop micro-fluidic chip according to claim 1, which is characterized in that the connecting pole (21) of rest part is worn
If the connecting hole (31) diameter and quantity be respectively D and N, the area of the supporting layer (30) is S, wherein 2S/25 π
D2≤N≤S/2πD2, D is 1~10mm.
5. drop micro-fluidic chip according to claim 1, which is characterized in that the runner (22) include respectively with it is described
Asphalt channel (221), the sample of the corresponding connection of oil pocket (212), the sample cavity (211) and the drop collecting chamber (213) are logical
Road (222) and drop channel (223).
6. drop micro-fluidic chip according to claim 1, which is characterized in that the drop micro-fluidic chip further includes folding
Set in the top of the supporting layer (30) and be centered around the fence (32) of the sealant (40) surrounding, the fence (32) and institute
State supporting layer (30) integrated molding or seperated molding.
7. drop micro-fluidic chip according to claim 6, which is characterized in that the sealant (40), multiple companies
Connect column (21), the flow channel layer (20) forms the first flexible chip, the fence (32) and the supporting layer (30) formation hard
Chip, the bottom plate (10) form the second flexible chip, and it is soft by method of molding to mold described first in the hard cores on piece
Property chip, second flexible chip are molded also by method of molding.
8. drop micro-fluidic chip according to claim 7, which is characterized in that the sealant (40), the connecting pole
(21) and the flow channel layer (20) and the bottom plate (10) are PDMS material, and/or, the supporting layer (30) and the fence
(32) it is stiff polymer material.
9. drop micro-fluidic chip according to claim 7, which is characterized in that the thickness of the flow channel layer (20) is 0.5
~5mm, and/or, the thickness of the bottom plate (10) is 0.5~10mm, and/or, the thickness of the supporting layer (30) is 1~
10mm, and/or, the thickness of the fence (32) and the sealant (40) is 0.5~5mm.
10. the molding machine of the drop micro-fluidic chip described in a kind of any one of molding claim 1 to 9, feature exist
In, including：Runner molding machine and baseplate molding device, the runner molding machine include：
First base (50), the first base (50) have first to place groove (53)；
Mold (60) is placed on described first and places in groove (53), and the surface of the mold (60) is equipped with for generating
State the molding structure of runner (22)；
First profiled sheeting (70), is stacked in the top of the first base (50), and first profiled sheeting (70) has placed cavity
(71), the supporting layer (30) is placed in the placed cavity (71)；
Fixed plate (80) is arranged on first profiled sheeting (70) and has multiple mounting holes (81)；
Multiple shaping columns (90), multiple shaping columns (90) are each passed through the corresponding mounting hole (81) and are inserted into the support
In the part connecting hole (31) on layer (30), the diameter D2 of the shaping column (90) is less than the corresponding connecting hole (31)
Diameter D1, the mold (60), first profiled sheeting (70), the supporting layer (30) and the shaping column (90) formed at
Cavity.
11. molding machine according to claim 10, which is characterized in that the diameter D2 and phase of each shaping column (90)
The diameter D1 of corresponding each connecting hole (31), meets following relationship：1.2×D2≤D1≤2×D2.
12. molding machine according to claim 10, which is characterized in that the first base (50) is equipped with first and fixes
Hole (51), first profiled sheeting (70) are equipped with the second mounting hole (72), and the runner molding machine further includes the first connection
Part (100), first connector (100) pass through from second mounting hole (72) and are fixed on first mounting hole
(51)；
The first base (50) is equipped with first positioning hole (52), and first profiled sheeting (70) is equipped with second location hole
(73), the fixed plate (80) is equipped with third location hole (82), and the runner molding machine further includes locating piece (110), institute
State locating piece (110) successively from the third location hole (82), the second location hole (73) pass through afterwards with it is described first positioning
Hole (52) coordinates.
13. molding machine according to claim 10, which is characterized in that the baseplate molding device includes：
Second base (120) has second to place groove (121)；
It is molded egative film (122), described second is placed on and places in groove (121), the surfacing light of the molding egative film (122)
It is sliding；
Second profiled sheeting (140) is stacked in the top of the molding egative film (122) and with corresponding to the molding egative film
(122) forming through hole (141)；
Second connector (150), second profiled sheeting (140) and the second base (120) pass through second connector
(150) it connects.
14. a kind of molding machine using described in any one of claim 11 to 13 prepares the preparation of drop micro-fluidic chip
Method, which is characterized in that include the following steps：
The mold (60) is placed on described first to place in groove (53), first profiled sheeting (70) is stacked in described the
On one pedestal (50), it will be sealed between the mold (60) and first profiled sheeting (70) by sealing material, by institute
It states supporting layer (30) to be placed in the placed cavity (71), pass through between the supporting layer (30) and first profiled sheeting (70)
Sealing material seals, and the fixed plate (80) is placed on first profiled sheeting (70), and the shaping column (90) are inserted into
Into the mounting hole (81)；
By certain mass than preparing PDMS, after being sufficiently stirred, exclusion bubble is vacuumized, liquid PDMS is passed through into the connecting hole
(31) it is poured slowly into forming cavity, stands the molding that is heating and curing after PDMS Self-levelings；
The fixed plate (80), the shaping column (90) are removed successively, and the part after solidification is taken from the placed cavity (71)
Go out, completes demoulding；
Face to be bonded is handled to the part and bottom plate (10), is bonded rapidly after processing, airtight passage is formed.
15. preparation method according to claim 14, which is characterized in that the baseplate molding device includes：Second base
(120), second places groove (121)；It is molded egative film (122), described second is placed on and places in groove (121), it is described
The surfacing for being molded egative film (122) is smooth；Second profiled sheeting (140) is stacked in the top of the molding egative film (122) and tool
There is the forming through hole (141) corresponding to the molding egative film (122),
Further include following steps before to the bottom plate (10) processing face to be bonded：
Second that the molding egative film (122) is placed on the second base (120) is placed in groove (121), by described the
Two profiled sheetings (140) are stacked in the second base (120), and liquid PDMS is poured into the institute of second profiled sheeting (140)
It states in forming through hole (141), stands the molding that is heating and curing after PDMS Self-levelings；
Bottom plate (10) is taken out from the forming through hole (141), completes demoulding.
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| CN109926112A (en) * | 2019-04-10 | 2019-06-25 | 中南大学 | The layered manufacturing method of three-dimensional microstructures polymeric micro-fluidic chip |
| CN112387316A (en) * | 2019-08-19 | 2021-02-23 | 中国科学院亚热带农业生态研究所 | 3D micro-fluidic chip model, 3D micro-fluidic chip, and preparation method and application thereof |
| CN112387316B (en) * | 2019-08-19 | 2021-09-21 | 中国科学院亚热带农业生态研究所 | 3D micro-fluidic chip model, 3D micro-fluidic chip, and preparation method and application thereof |
| CN112844501A (en) * | 2019-11-28 | 2021-05-28 | 中国科学院大连化学物理研究所 | Multi-liquid-core hydrogel microcapsule chip based on double aqueous phases and application thereof |
| WO2023019447A1 (en) * | 2021-08-17 | 2023-02-23 | 京东方科技集团股份有限公司 | Control valve structure and usage method therefor, microfluidic chip, and nucleic acid extraction device |
| CN115254216A (en) * | 2022-07-21 | 2022-11-01 | 苏州索真生物技术有限公司 | Method for processing micro-fluidic chip |
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