CN114950584B - Three-dimensional micro-channel chip structure for generating liquid drops and manufacturing method - Google Patents

Three-dimensional micro-channel chip structure for generating liquid drops and manufacturing method Download PDF

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CN114950584B
CN114950584B CN202210451067.1A CN202210451067A CN114950584B CN 114950584 B CN114950584 B CN 114950584B CN 202210451067 A CN202210451067 A CN 202210451067A CN 114950584 B CN114950584 B CN 114950584B
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CN114950584A (en
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赵才明
马盛林
夏雁鸣
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Xiamen University
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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
    • B81MICROSTRUCTURAL TECHNOLOGY
    • B81BMICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B7/00Microstructural systems; Auxiliary parts of microstructural devices or systems
    • B81B7/02Microstructural systems; Auxiliary parts of microstructural devices or systems containing distinct electrical or optical devices of particular relevance for their function, e.g. microelectro-mechanical systems [MEMS]
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/061Counting droplets
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0636Focussing flows, e.g. to laminate flows
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0883Serpentine channels
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B81MICROSTRUCTURAL TECHNOLOGY
    • B81BMICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B2201/00Specific applications of microelectromechanical systems
    • B81B2201/05Microfluidics

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Abstract

The invention discloses a three-dimensional micro-channel chip structure for generating liquid drops and a manufacturing method thereof, comprising five micro-channel layers which are arranged up and down, wherein a first micro-channel layer and a second micro-channel layer are used for introducing and shunting a first phase and a second phase, a third micro-channel layer is provided with mixing units which are arranged in a matrix manner and are used for mixing the first phase and the second phase, a fourth micro-channel process is provided with liquid drop release units which are in one-to-one correspondence with the mixing units and are used for forming liquid drops after mixing the first phase and the second phase, and a fifth micro-channel is used for collecting and extracting the liquid drops. The invention solves the problem that the planar liquid drop generating chip can produce fewer liquid drops, reduces the occupied area of a single liquid drop generating module by using a three-dimensional micro-channel, can realize the liquid drop yield of a plurality of liters per hour through matrix arrangement, and is expected to realize annual ton level.

Description

Three-dimensional micro-channel chip structure for generating liquid drops and manufacturing method
Technical Field
The invention belongs to the technical field of micromachining, and particularly relates to a three-dimensional micro-channel chip structure for generating liquid drops and a manufacturing method thereof.
Background
The traditional liquid drops are generated by adopting methods such as an oscillation method, a stirring method, ultrasonic emulsification and the like, and are applied to the fields of fixed-point transportation of foods, cosmetics and medicines and the like. With the rapid development of biological detection technology and micro-nano materials, micro-nano-sized liquid drops start to be applied to the work of biological detection of micro-molecules, preparation of micro-capsules, preparation of micro-nano particles and the like.
For the preparation of microcapsules and micro-nanoparticles, how to realize high-throughput droplet generation is a key to commercialization of droplet generation chips. The number of parallel liquid drop generating modules is increased in a parallel array mode by the existing plane microfluidic liquid drop generating chip, glass-silicon-glass materials are adopted, wherein the length of a single plane liquid drop generating module is 1.4mm, the width of the single plane liquid drop generating module is 80um, the size of generated liquid drops is 21-28um, the highest per-hour yield reaches the ascending order, and the yield of liquid drops needs to be further improved.
Disclosure of Invention
Aiming at the problems and the defects of the prior art, the invention discloses a three-dimensional array type three-dimensional micro-channel chip structure applied to droplet generation and a manufacturing method thereof.
In order to achieve the above object, the technical scheme of the present invention is as follows:
a three-dimensional micro-channel chip structure for generating liquid drops,
the beneficial effects of the invention are as follows:
1) The chip three-dimensional array type micro-flow channel structure for generating micro-fluid liquid drops and the manufacturing method thereof are provided, the problem that the planar micro-fluid liquid drop generating chip can generate fewer liquid drops is solved, the three-dimensional micro-flow channel is used for reducing the occupied area of a single liquid drop generating flow channel, and the size of a fluid shearing position can be as small as 1-2um;
2) Through the three-dimensional micro-channel of array type, the droplet size is in the range of 5um to hundreds of um, and can reach the higher output of several liters of droplets per hour, be expected to realize the production of ton class each year.
Drawings
FIG. 1 is a three-dimensional array micro-channel structure;
FIG. 2 is a disassembled view of a three-dimensional array micro-channel structure;
FIG. 3 is a cross-sectional view of a three-dimensional array micro-fluidic channel structure;
FIG. 4 is a schematic diagram (three-dimensional diagram) of three-dimensional array micro-channel droplet generation;
FIG. 5 is a schematic diagram (cross-sectional view) of three-dimensional array micro-channel droplet generation;
fig. 6-12 are flow charts of three-dimensional array micro-fluidic channel manufacturing process.
Figure BDA0003618641260000021
Detailed Description
The invention is further explained below with reference to the drawings and specific embodiments. The drawings of the present invention are merely schematic to facilitate understanding of the present invention, and specific proportions thereof may be adjusted according to design requirements.
The present example discloses a three-dimensional array micro-fluidic chip structure for droplet generation, which can refer to fig. 1-3, and includes five micro-fluidic channel layers, namely, a first micro-fluidic channel layer 100, a second micro-fluidic channel layer 200, a third micro-fluidic channel layer 300, a fourth micro-fluidic channel layer 400 and a fifth micro-fluidic channel layer 500 from bottom to top.
The first microchannel layer 100 has a first vertical microchannel 101 and a first half-open planar microchannel 102;
the second microchannel layer 200 has a second vertical microchannel 201;
the third microchannel layer 300 has a second semi-open planar microchannel 301, a third vertical microchannel 302, and a third semi-open planar microchannel 303;
the fourth microchannel layer 400 has a fourth vertical microchannel 401 and a fifth vertical microchannel 402;
the fifth microchannel layer 500 has a fourth half-open planar microchannel 501 and a sixth vertical microchannel 502.
If the micro-channel chip structure is used for generating oil droplets in water, the micro-channel wall needs to have hydrophilicity; if water-in-oil droplets are to be produced, the walls of the microchannels need to be hydrophobic. The hydrophilicity and hydrophobicity of the microchannels can be achieved by material selection or surface modification of the channel walls.
The five micro-channel layers are stacked and communicated to form a plurality of channels for introducing, splitting and collecting fluid, for example, when the micro-channel layers are used for generating liquid drops by continuous phase fluid and discrete phase fluid:
the first half open-type planar micro-channel 102 is divided into a continuous phase dispersion channel 105 and a discrete phase dispersion channel 106 which are designed in an interdigital manner, and the first vertical micro-channel 101 is divided into a continuous phase inlet 103 and a discrete phase inlet 104 which are communicated with the continuous phase dispersion channel 105 and the discrete phase dispersion channel 106 in one-to-one correspondence; the first microchannel layer 100 is used for independent entry and transport of multiphase fluid;
the second vertical micro flow channel 201 is divided into a plurality of continuous phase flow channels 202 and discrete phase flow channels 203 respectively communicating with the continuous phase dispersion flow channels 105 and the discrete phase dispersion flow channels 106; the second micro flow channel layer 200 is used for splitting fluid;
the third micro-channel layer 300 forms a plurality of mixing units which are arranged in an array manner, each mixing unit is formed by combining a second semi-open type plane micro-channel 301, a third vertical micro-channel 302 and a third semi-open type plane micro-channel 303 from bottom to top, is divided into a continuous phase channel 304 and a discrete phase channel 305, and is correspondingly communicated with the continuous phase channel 202 and the discrete phase channel 203 respectively, so that the continuous phase and the discrete phase respectively enter the mixing units; in this embodiment, each mixing unit is connected to 1 discrete phase flow channel 203 and 2 continuous phase flow channels 202, and the discrete phase flow channels 203 are located between the two continuous phase flow channels 202; the second semi-open planar micro-fluidic channel 301 has a serpentine channel structure to serve as a fluid flow resistance channel to ensure consistent dynamic pressure of the continuous phase and the discrete phase entering the mixing unit; the third semi-open planar fluidic channel 303 forms a fluid pool that communicates the continuous phase channel 304 with the discrete phase channel 305.
The fourth vertical micro-flow channel 401 and the fifth vertical micro-flow channel 402 are connected up and down one by one to form a liquid drop release unit, and are communicated with the mixing units one by one, the fourth vertical micro-flow channel 401 forms fluid shearing, the fifth vertical micro-flow channel 402 is used for releasing liquid drops, and the fluid of each mixing unit is mixed to form liquid drops on the fourth micro-flow channel layer 400; that is, the third and fourth micro flow channel layers 300 and 400 are combined to form a single droplet generation module, and a plurality of modules are arranged in an array.
The fifth vertical micro-channel 402, the fourth half-open planar micro-channel 501 and the sixth vertical micro-channel 502, wherein the fourth half-open planar micro-channel 501 is used for collecting liquid drops, and the sixth vertical micro-channel 502 is provided with a liquid drop outlet for leading out liquid drops.
For the three-dimensional array micro-channel chip structure for generating the liquid drops, referring to fig. 4 to 5, the continuous phase and the discrete phase fluid respectively pass through the first micro-channel layer, the second micro-channel layer, the third micro-channel layer and the fourth micro-channel layer to form the liquid drops, and the liquid drops are collected and led out by utilizing the fifth micro-channel layer.
First, the continuous phase fluid 602 is introduced into the micro flow channel through the continuous phase inlet 103, and the discrete phase fluid 601 reaches the single droplet generation module through the continuous phase dispersion flow channel 105 and the discrete phase dispersion flow channel 106 after being introduced into the micro flow channel through the discrete phase inlet 104. Further, after the fluid flowing through the continuous phase runner 202 (discrete phase runner 203), the second semi-open planar micro runner 301, and the continuous phase runner 304 (discrete phase runner 305) to the third semi-open planar micro runner 303 is converged, the fluid is converged in the fourth vertical micro runner 401 and forms a droplet 603 through the fifth vertical micro runner 402. Finally, droplets are generated at the same positions in the array as the fourth vertical micro flow channel 401 and the fifth vertical micro flow channel 402, and are communicated with the fourth semi-open planar micro flow channel 501, and a large number of droplets are led out through the sixth vertical micro flow channel 502. By controlling the flow rate (ul/min) of the continuous phase fluid and the discrete phase fluid entering the chip and the size of the shearing place of the micro-channel fluid to reach a scale of several micrometers/tens of micrometers, the generation of liquid drops with the level of 5um to hundreds of um can be realized.
The fluid flow resistance channel designed in the third micro flow channel layer 300 ensures that dynamic pressures of the continuous phase and the disperse phase entering each droplet generation module in the array are consistent. Tens of thousands of single three-dimensional micro-channel array droplet generation modules are arranged in an array mode, namely droplets of a few liters per hour are generated.
With further reference to fig. 6-12, the present example also discloses a method for manufacturing a three-dimensional array micro-fluidic chip for generating oil droplets in water, comprising the following steps:
step 1, as shown in fig. 6 (a), the first micro flow channel layer 100 uses polydimethylsiloxane as a substrate, and a first vertical micro flow channel 101 is processed on a lower surface 110 by a polymer replication forming technology, and as shown in fig. 6 (b), a first half open planar micro flow channel 102 is processed on an upper surface 120, and the first vertical micro flow channel 101 is communicated with the first half open planar micro flow channel 102, and a hydrophilic coating is formed on the micro flow channel;
step 2, as shown in fig. 7, the second micro flow channel layer 200 uses glass as a substrate, and a second vertical micro flow channel layer 201 communicating the lower surface 210 and the upper surface 220 can be formed by a laser processing technology;
step 3, as shown in fig. 8 (a), the third micro-channel layer 300 uses silicon as a substrate, and a second semi-open planar micro-channel 301 is etched on the lower surface 310 by a deep reactive ion etching technology, as shown in fig. 8 (b), and a third semi-open planar micro-channel 303 is etched on the upper surface 320, as shown in fig. 8 (c), and a third vertical micro-channel 302 is processed downward in the second semi-open planar micro-channel 303;
step 4, as shown in fig. 9 (a), after the fifth vertical micro flow channel 402 is processed on the upper surface 420 by using glass as a substrate in the fourth flow channel layer 400 and the fifth vertical micro flow channel 401 is processed on the lower surface 410 by using a laser processing technique, as shown in fig. 9 (b);
step 5, as shown in fig. 10 (a), the fifth micro flow channel layer 500 uses polydimethylsiloxane as a substrate, and a fourth half open type planar micro flow channel 501 is processed on the lower surface 510 by a polymer replication forming technology, as shown in fig. 10 (b), a sixth vertical micro flow channel 502 is processed on the upper surface 120, and the fourth half open type planar micro flow channel 501 is communicated with the sixth vertical micro flow channel 502, and a hydrophilic coating is formed on the micro flow channel;
step 6, as shown in fig. 11, bonding the second runner layer 200 and the fourth runner layer 400 on both sides of the third runner layer 300 by using a silicon glass anodic bonding process, so as to communicate the second vertical runner layer 201, the second semi-open planar runner 301, the third vertical runner 302, the third semi-open planar runner 303, the fourth vertical runner 401 and the fifth vertical runner 402;
step 7, as shown in fig. 12, a plasma bonding method is adopted on the basis of step 7, a first micro-channel layer 100 is bonded on the lower surface of the second micro-channel layer 200, and a fifth micro-channel layer 100 is bonded on the upper surface of the fourth micro-channel layer 400, so that the communication between the first vertical micro-channel 101 and the sixth vertical micro-channel is realized.
The minimum characteristic dimension of the micro-channel can reach 1-2um, and can be controlled to be tens or hundreds of micrometers; the footprint of a single droplet generation module is less than 1mm by 50um.
The substrate in the step 1 and the step 5 can be selected from silicon, glass, teflon, acrylic or other high polymer materials besides polydimethylsiloxane; in the steps 1 and 5, a polymer replication forming technology is adopted, and a deep reactive ion etching technology, a laser induced etching rapid forming technology, a wet etching or hot embossing technology, a laser ablation or sand blasting or ultrasonic micromachining, CNC machining and other methods can be selected;
in the step 2 and the step 4, the substrate can be selected from silicon, teflon, acrylic, polydimethylsiloxane or other high polymer materials besides glass serving as a base; in the steps 2 and 4, a laser processing technology is adopted, and a deep reactive ion etching technology, a laser induced etching rapid forming technology, a wet etching technology, a hot embossing technology, a laser ablation technology, a sand blasting technology, an ultrasonic micromachining technology, a CNC machining technology and the like can be selected;
in the step 3, the substrate can be selected from glass, teflon, acrylic, polydimethylsiloxane or other high polymer materials besides silicon as a base; in the step 3, a deep reactive ion etching technology is adopted, and a laser induced etching rapid forming technology, a wet etching or hot embossing technology, a laser ablation or sand blasting or ultrasonic micromachining or CNC machining and other methods can be selected;
in the step 6, besides the silicon glass anode bonding process, thermal bonding, adhesive bonding, bonding of a metal intermediate layer, low-temperature bonding technology and other methods can be adopted.
In the step 7, besides the plasma bonding method, thermal bonding, adhesive bonding, bonding of a metal intermediate layer, low-temperature bonding technology and the like can be adopted.
The above embodiments are only used for further illustrating a three-dimensional array micro-fluidic chip structure for droplet generation and a method for manufacturing the same, but the invention is not limited to the embodiments, and any simple modification, equivalent variation and modification of the above embodiments according to the technical substance of the invention falls within the scope of the technical solution of the invention.

Claims (7)

1. A three-dimensional micro-channel chip structure for droplet generation which characterized in that: the micro-fluidic device comprises a first micro-fluidic channel layer, a second micro-fluidic channel layer, a third micro-fluidic channel layer, a fourth micro-fluidic channel layer and a fifth micro-fluidic channel layer from bottom to top;
the first micro-channel layer is provided with a first vertical micro-channel for fluid to enter and a first half-open plane micro-channel for fluid to disperse; the first half open type plane micro-flow channel is divided into a first phase dispersion flow channel and a second phase dispersion flow channel which are designed in an interdigital way, and the first vertical micro-flow channel is divided into a first phase inlet and a second phase inlet which are communicated with the first phase dispersion flow channel and the second phase dispersion flow channel in a one-to-one correspondence way;
the second micro-channel layer is provided with a plurality of second vertical micro-channels which are arranged in an array manner; the first vertical micro-flow channel, the first half open type plane micro-flow channel and the second vertical micro-flow channel form a first-phase flow channel and a second-phase flow channel which are mutually independent;
the third micro-channel layer is provided with a plurality of mixing units which are arranged in an array manner, and each mixing unit is formed by combining a second semi-open type plane micro-channel, a third vertical micro-channel and a third semi-open type plane micro-channel from bottom to top; each mixing unit is communicated with a second vertical micro-channel of the first phase and a second vertical micro-channel of the second phase and is used for mixing the first phase and the second phase; the first and second phases are continuous and discrete phase fluids that form droplets through the mixing unit and droplet discharge unit; the mixing unit is communicated with two continuous phase second vertical micro-channels and one discrete phase second vertical micro-channel, the discrete phase second vertical micro-channel is positioned between the two continuous phase second vertical micro-channels, and the discrete phase and the continuous phase are mixed in the third semi-open plane micro-channel;
the fourth micro-channel layer is provided with liquid drop release units which are communicated with the outlets of the mixing units in a one-to-one correspondence manner, and each liquid drop release unit is formed by combining a fourth vertical micro-channel and a fifth vertical micro-channel respectively;
the fifth microchannel layer has a fourth half-open planar microchannel for converging the droplets formed by the droplet discharge unit and a sixth vertical microchannel for droplet extraction.
2. The three-dimensional fluidic channel chip structure for droplet generation according to claim 1, wherein: the fourth vertical micro-channel is connected with the outlet of the mixing unit and used for forming fluid shearing, and the size range of the fourth vertical micro-channel is 1-100 mu m.
3. The three-dimensional fluidic channel chip structure for droplet generation according to claim 1, wherein: the second semi-open planar micro-channel has a serpentine channel structure for enabling dynamic pressure of the first phase and the second phase entering the plurality of mixing units arranged in an array to be consistent as a fluid flow resistance channel.
4. The three-dimensional fluidic channel chip structure for droplet generation according to claim 1, wherein: the mixing unit and the droplet discharging unit form a droplet generating module, and the occupied area of the droplet generating module is smaller than 1mm by 50 mu m.
5. A method for manufacturing a three-dimensional fluidic channel chip structure for droplet generation according to any one of claims 1 to 4, characterized by: the method comprises the following steps:
1) The first micro-channel layer adopts a first substrate, a first vertical micro-channel is processed on the lower surface, a first half-open type plane micro-channel is processed on the upper surface, and the first vertical micro-channel is communicated with the first half-open type plane micro-channel;
2) The second micro-channel layer adopts a second substrate to form a second vertical micro-channel layer communicated with the lower surface and the upper surface;
3) The third micro-channel layer adopts a third substrate, a second semi-open type plane micro-channel is processed on the lower surface, a third semi-open type plane micro-channel is processed on the upper surface, and a third vertical micro-channel is processed downwards in the second semi-open type plane micro-channel;
4) The fourth micro-channel layer adopts a fourth substrate, and a fourth vertical micro-channel is processed on the lower surface after a fifth vertical micro-channel is processed on the upper surface;
5) The fifth micro-channel layer adopts a fifth substrate, a fourth half-open type plane micro-channel is processed on the lower surface, a sixth vertical micro-channel is processed on the upper surface, and the fourth half-open type plane micro-channel is communicated with the sixth vertical micro-channel;
6) Bonding a second substrate and a fourth substrate on two sides of the third substrate respectively to communicate the second vertical micro-channel layer, the second semi-open planar micro-channel, the third vertical micro-channel, the third semi-open planar micro-channel, the fourth vertical micro-channel and the fifth vertical micro-channel;
7) And bonding the first substrate on the lower surface of the second substrate, and bonding the fifth substrate on the upper surface of the fourth substrate, so that the communication from the first vertical micro-channel to the sixth vertical micro-channel is realized.
6. The manufacturing method according to claim 5, characterized in that: the materials of the first substrate, the second substrate, the third substrate, the fourth substrate and the fifth substrate comprise polydimethylsiloxane, acrylic, silicon, glass or Teflon; in the steps 1) to 5), the processing includes a polymer replication forming technology, a deep reactive ion etching technology, a laser induced etching rapid prototyping technology, wet etching, a hot embossing technology, laser ablation, sand blasting, ultrasonic micromachining or CNC machinery.
7. The manufacturing method according to claim 5, characterized in that: in the step 6) and the step 7), the bonding comprises thermal bonding, adhesive bonding, metal interlayer bonding or low-temperature bonding.
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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
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