CN117244599B - Method for manufacturing PDMS micro-fluidic chip - Google Patents

Method for manufacturing PDMS micro-fluidic chip Download PDF

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Publication number
CN117244599B
CN117244599B CN202311516236.6A CN202311516236A CN117244599B CN 117244599 B CN117244599 B CN 117244599B CN 202311516236 A CN202311516236 A CN 202311516236A CN 117244599 B CN117244599 B CN 117244599B
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paraffin
micro
pdms
substrate
model
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CN117244599A (en
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刘金刚
陈琛
李明富
肖育劲
彭远刚
王浩新
宋奎
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Xiangtan University
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Xiangtan 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
    • 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

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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

Firstly, cutting a chip substrate according to the outline dimension of the micro-fluidic chip, and then cleaning the substrate; then casting paraffin on the substrate, and processing the paraffin into a microchannel shape comprising an outlet model and an inlet model; molding paraffin by using a PDMS mixed material containing a curing agent and a coagent to obtain a micro-fluidic chip crude product; and finally, heating the crude product, blowing air into the micro-channel to blow out paraffin in the micro-channel, and cleaning and drying to finish the manufacturing of the micro-fluidic chip. The method comprises the steps of processing a model comprising an outlet and an inlet of the microfluidic chip on a substrate by paraffin, then molding the model by PMDS, directly combining the PMDS with the substrate, and then removing the paraffin model, so that a complete microfluidic chip is obtained, the step of combining an upper cover with a negative film is not needed, and the microfluidic chips with various shapes can be flexibly manufactured.

Description

Method for manufacturing PDMS micro-fluidic chip
Technical Field
The application belongs to the field of microfluidic chips, and particularly relates to a manufacturing method of a microfluidic chip made of PDMS (polydimethylsiloxane) material.
Background
The microfluidic chip is a small-volume detection chip integrating a series of operations such as sample injection, reaction, detection and the like, has low cost, portability, simple and convenient operation, less reagent consumption, high analysis speed, good biocompatibility, multiple detection and the like, and has wide application prospect. The manufacturing method of the microfluidic chip comprises 3D printing, injection molding, pouring and the like, wherein a model of a microchannel is required to be manufactured, a cover plate and a base plate are respectively manufactured, then the cover plate and the base plate are combined into a whole, as in the patent application of the invention with the application number of CN201410149225 and the name of a preparation method of the PDMS microfluidic chip, a paraffin male die is firstly manufactured on a glass substrate, then a PDMS negative die is manufactured on the paraffin male die, and finally the PDMS negative die is bonded with the glass substrate to form the PDMS microfluidic chip; the invention patent application with the application number of CN202310040423, named as a PMMA microfluidic chip packaging method and PMMA microfluidic chip, discloses how to package a bottom plate and a cover plate into the PMMA microfluidic chip.
The processing process is complex, the manufacturing period is long, and the requirements on equipment and processing environment are high. For a small number of custom microfluidic chips, none of the above approaches is flexible enough.
Disclosure of Invention
Aiming at the problem that the current microfluidic chip needs additional packaging to cause slower speed, the method for manufacturing the PDMS microfluidic chip is provided, the complete PDMS microfluidic chip can be directly processed on the substrate, and no additional packaging step is needed, so that the flexibility is higher.
The technical means adopted by the application for solving the problems are as follows: firstly, cutting a chip substrate according to the outline dimension of the micro-fluidic chip, and then cleaning the substrate; then casting paraffin on the substrate, and processing the paraffin into a microchannel shape comprising an outlet model and an inlet model; molding paraffin by using a PDMS mixed material containing a curing agent and a coagent to obtain a micro-fluidic chip crude product; and finally, heating the crude product, blowing air into the micro-channel to blow out paraffin in the micro-channel, and cleaning and drying to finish the manufacturing of the micro-fluidic chip. The PDMS mixed material cover plate is directly connected with the substrate in the forming process, so that the subsequent packaging step is omitted.
Further, the paraffin thickness is greater than or equal to the depth at the outlet and inlet of the microfluidic chip. To ensure that the shapes of the outlet and inlet models can be machined in paraffin.
Further, when paraffin is molded, the thickness of the PDMS mixed material is equal to or less than the height at the outlet and inlet molds formed of paraffin. So as to ensure that the outlet and the inlet after the microfluidic chip is formed can be directly communicated with the outside.
Further, the chip substrate comprises a glass silicon wafer or one of PMMA polymers and PDMS polymers.
Further, the cleaning mode of the glass silicon wafer is as follows: placing the glass silicon wafer into a solution containing 98% concentrated sulfuric acid and 30% hydrogen peroxide (volume ratio is 3:1 or 4:1) for micro-boiling treatment for 30 minutes so as to remove an oxide layer and metal impurities on the surface; then taking out the glass silicon wafer, and cleaning the glass silicon wafer by using absolute ethyl alcohol to remove residual acidic substances and organic matters; and finally, putting the glass silicon wafer into a baking oven at 100 ℃ for baking so as to remove the moisture on the surface.
Further, the polymer is cleaned by the following steps: soaking the polymer in absolute ethanol for 15 minutes to dissolve grease and dust on the surface; then taking out the polymer, and cleaning the polymer with deionized water to remove residual ethanol and impurities; and finally, putting the polymer into a 60 ℃ oven for drying so as to remove the moisture on the surface.
Further, the paraffin wax is heated to a molten state prior to casting.
Further, the liquid drop micro-jetting device is adopted to jet paraffin, so that the thickness and uniformity are ensured to meet the requirements of chip channels.
Further, the composition of the curing agent comprises the following components:
an amino compound selected from the group consisting of 3-aminopropyl triethoxysilane, 3-aminopropyl trimethoxysilane, 3-aminopropyl methyldiethoxysilane, in an amount of 0.5 to 2eq;
an alkoxy-containing halogenated phenol selected from 3-methoxy-4-chlorophenol, wherein the weight of the alkoxy-containing halogenated phenol is 0.8-2eq;
an inorganic carbonate selected from sodium carbonate, potassium carbonate, or a mixed solution thereof, the weight of which is 3-6eq;
a catalyst selected from potassium iodide, in an amount of 0.1 to 0.3eq;
a polar organic solvent selected from DMF, which is 20-100eq by weight.
Further, the preparation method of the composition of the curing agent comprises the following steps:
mixing the components according to molar equivalent proportion, blowing nitrogen to remove oxygen for 3-5 times, each time for 10min, and reacting for 12-24h at 80-100 ℃ under the protection of nitrogen;
after the reaction is finished, removing inorganic salt by suction filtration, and concentrating to remove organic solvent;
vacuum drying to obtain the curing agent composition.
Further, mixing PDMS with the composition of the curing agent and the active auxiliary agent according to the proportion of 10 (1-3) (0.1-1), and vacuumizing to remove bubbles; after the molding of the PDMS material was completed, the air bubbles were removed again by vacuum suction, and then allowed to stand for curing.
Further, the standing time is 24 hours or longer.
The beneficial effects of this application are:
1. the method comprises the steps of processing a model comprising an outlet and an inlet of the microfluidic chip on a substrate by paraffin, then molding the model by PMDS, directly combining the PMDS with the substrate, and then removing the paraffin model, so that a complete microfluidic chip is obtained, the step of combining an upper cover with a negative film is not needed, and the microfluidic chips with various shapes can be flexibly manufactured.
2. The paraffin model is blown out of the micro-channel after being heated, so that the shape and the size of the micro-channel in the formed micro-fluidic chip can be guaranteed.
3. According to the method, the self-made curing agent composition is added, so that the PDMS can be cured at room temperature, the interface bonding performance is improved, the processing performance is good, the reaction speed is high, and the operation time is long.
Drawings
FIG. 1 is a schematic diagram of a substrate structure according to an embodiment;
FIG. 2 is a schematic diagram of a paraffin model fabricated on a substrate according to one embodiment;
FIG. 3 is a schematic diagram of a molding structure of paraffin wax using PDMS material;
FIG. 4 is a schematic diagram of a micro-fluidic chip according to an embodiment II;
in the figure: 1. the substrate, 2, paraffin model, 21, outlet model, 22, inlet model, 3.PDMS cover.
Detailed Description
The present application is further described below with reference to the accompanying drawings. Wherein the drawings are for illustrative purposes only and are shown in schematic, non-physical, and not intended to be limiting; for the purpose of better illustrating embodiments of the present application, certain elements of the drawings may be omitted, enlarged or reduced and do not represent the size of the actual product; it will be appreciated by those skilled in the art that certain well-known structures in the drawings and descriptions thereof may be omitted.
Embodiment one: as shown in fig. 1-3, a method for manufacturing a PDMS microfluidic chip includes the following steps:
the first step: substrate 1 processing
Firstly, according to the outline dimension of the micro-fluidic chip, a chip substrate 1 is manufactured through cutting, wherein the substrate 1 can be a glass silicon wafer or a sheet-shaped structure made of polymers such as PMMA, PDMS and the like.
The substrate 1 is then cleaned. (1) cleaning a glass silicon wafer: placing the glass silicon wafer into a solution containing 98% concentrated sulfuric acid and 30% hydrogen peroxide (volume ratio is 3:1 or 4:1) for micro-boiling treatment for 30 minutes so as to remove an oxide layer and metal impurities on the surface; then the glass silicon wafer is taken out and washed by absolute ethyl alcohol so as to remove residual acidic substances and organic matters; and finally, putting the glass silicon wafer into a baking oven at 100 ℃ for baking so as to remove the moisture on the surface. (2) cleaning of the polymer: soaking the polymer in absolute ethanol for 15 minutes to dissolve grease and dust on the surface; then taking out the polymer, and cleaning the polymer with deionized water to remove residual ethanol and impurities; and finally, putting the polymer into a 60 ℃ oven for drying so as to remove the moisture on the surface.
And a second step of: paraffin model making
The paraffin is heated to a molten state and then the molten paraffin is poured onto the substrate 1 to form a uniform paraffin layer, and the thickness of the paraffin is consistent with the maximum depth of the desired micro-channels. The paraffin is sprayed by adopting a liquid drop micro-spraying device so as to ensure that the thickness and uniformity meet the requirements of chip channels.
And finally, cutting the paraffin layer by adopting a precise numerical control milling machine and a superhard cutter (such as a diamond cutter) according to the channel size of the microfluidic chip to form a microchannel shape, and cleaning the paraffin scraps remained after cutting to obtain a paraffin model 2 of the microchannel with the outlet model 21 and the inlet model 22. The technological parameters adopted in the cutting process are as follows: spindle rotation speed is 8000-12000 r/min, cutting depth is 0.02-1mm, and feed rate is 0.6-15 mm/min.
The paraffin model 2 is integrally formed with the substrate 1 after being processed, and does not need to be removed from the substrate 1.
And a third step of: processing micro-fluidic chip
Curing agent and polyethylene glycol were added to PDMS in an amount of 10 (1-3) (0.1-1), and the mixture was uniformly mixed using a mechanical stirrer, and then the mixture was evacuated to remove bubbles. The PDMS can be solidified at room temperature, and meanwhile, the bonding performance is improved, so that the formed cover plate and the substrate 1 can be integrated under the condition of no external force or temperature.
And uniformly coating the PDMS mixed material on the substrate 1, completely covering the paraffin model 2 to mould the paraffin model 2, vacuumizing again to remove bubbles, standing for 24 hours to wait for solidification, and obtaining the PDMS cover plate 3 connected with the substrate 1 after solidification.
And finally, heating the solidified product to 150 ℃, and blowing compressed air into the inlet or the outlet of the chip after the paraffin in the micro-flow channel is melted, and pushing the melted paraffin in the micro-flow channel to blow out from the outlet or the inlet through the compressed air. And cleaning the micro-channel with clear water, and drying to finish the manufacturing of the micro-fluidic chip.
In this example, the curing agent was prepared as follows:
KH550 (0.11 mol,24.35 g), 3-methoxy-4-chlorophenol (0.12 mol,19.03 g), potassium iodide (0.02 mol,3.32 g), potassium carbonate (0.6 mol,82.92 g) were placed in a reaction vessel, and charged withN,N-Dimethylformamide (DMF) (5 mol,365g, 3838 mL). The reaction was stirred at 80℃for 24h under nitrogen protection. After the reaction is finished, filtering, taking out the supernatant, concentrating the solvent, and drying in vacuum to obtain the curing agent.
Embodiment two: as shown in fig. 4, the microfluidic chip may also be manufactured in a shape of a wafer, and at this time, the paraffin model 2 is molded by using a PDMS mixed material in a spin coating manner.
The figure only shows the simplest microchannel model, but the microchannels may have other complex structures, and multiple groups of microchannels with outlets and inlets may be arranged on a chip, and these structures may be implemented in the manner of this embodiment.
The above embodiments are provided for illustrating the present application and not for limiting the present application, and various changes and modifications may be made by one skilled in the relevant art without departing from the spirit and scope of the present application, so that all equivalent technical solutions should be also included in the scope of the present application, which should be defined by the claims.

Claims (5)

1. A manufacturing method of a PDMS micro-fluidic chip is characterized by comprising the following steps: firstly, cutting a chip substrate according to the outline dimension of a microfluidic chip, and cleaning the substrate; then casting paraffin on the substrate, and processing the paraffin into a microchannel shape comprising an outlet model and an inlet model; molding paraffin by using a PDMS mixed material containing a curing agent and a coagent to obtain a micro-fluidic chip crude product; finally heating the crude product, blowing air into the micro-channel to blow out paraffin in the micro-channel, and cleaning and drying to finish the manufacturing of the micro-fluidic chip;
the curing agent is a composition comprising an amino compound, an alkoxy-containing halogenated phenol inorganic carbonate, a catalyst and a polar organic solvent, and the preparation method of the composition of the curing agent is as follows: mixing the components according to molar equivalent proportion, blowing nitrogen to remove oxygen for 3-5 times, each time for 10min, and reacting for 12-24h at 80-100 ℃ under the protection of nitrogen; after the reaction is finished, removing inorganic salt by suction filtration, and concentrating to remove organic solvent; vacuum drying to obtain a curing agent composition;
wherein, the weight ratio of PDMS to curing agent and active auxiliary agent in the PDMS mixed material is: 10:1-3:0.1-1; the chip substrate comprises one of a glass silicon wafer, a PMMA polymer or a PDMS polymer;
the cleaning mode of the glass silicon wafer is as follows: placing the glass silicon wafer into a solution containing 98% concentrated sulfuric acid and 30% hydrogen peroxide for micro-boiling treatment for 30 minutes to remove an oxide layer and metal impurities on the surface, wherein the volume ratio of the 98% concentrated sulfuric acid to the 30% hydrogen peroxide is 3:1 or 4:1; then taking out the glass silicon wafer, and cleaning the glass silicon wafer by using absolute ethyl alcohol to remove residual acidic substances and organic matters; finally, the glass silicon wafer is put into a baking oven at 100 ℃ for baking so as to remove the moisture on the surface;
further, when the chip substrate adopts a PMMA polymer or a PDMS polymer, the polymer is cleaned by the following steps: soaking the polymer in absolute ethanol for 15 minutes to dissolve grease and dust on the surface; then taking out the polymer, and cleaning the polymer with deionized water to remove residual ethanol and impurities; finally, the polymer is put into a baking oven at 60 ℃ for baking so as to remove the moisture on the surface;
further, the paraffin wax is processed into the shape of the micro-channel comprising an outlet model and an inlet model, which is as follows: heating paraffin to a molten state, and then pouring the molten paraffin on a substrate to form a uniform paraffin layer, wherein the thickness of the paraffin is consistent with the maximum depth of a required microchannel, and the paraffin is sprayed by a droplet microjet device so as to ensure that the thickness and uniformity meet the requirements of a chip channel; and finally, cutting the paraffin layer by adopting a precise numerical control milling machine and a diamond cutter according to the channel size of the microfluidic chip to form a microchannel shape, and cleaning the paraffin scraps left after cutting to obtain a paraffin model of the microchannel with an outlet model and an inlet model.
2. The method for manufacturing the PDMS micro-fluidic chip according to claim 1, wherein: the paraffin is heated to a molten state before casting, and is sprayed by adopting a liquid drop micro-spraying device.
3. The method for manufacturing the PDMS micro-fluidic chip according to claim 1, wherein: the amino compound is selected from one of 3-aminopropyl triethoxysilane, 3-aminopropyl trimethoxysilane and 3-aminopropyl methyl diethoxysilane, and the weight of the amino compound is 0.5-2eq;
the alkoxy-containing halogenated phenol is 3-methoxy-4-chlorophenol with the weight of 0.8-2eq;
the inorganic carbonate is sodium carbonate, potassium carbonate or a mixed solution thereof with the weight of 3-6eq;
the catalyst is potassium iodide with the weight of 0.1-0.3eq;
the polar organic solvent is DMF with the weight of 20-100eq.
4. The method for manufacturing the PDMS micro-fluidic chip according to claim 1, wherein: the active auxiliary agent is polyethylene glycol.
5. The method for manufacturing the PDMS micro-fluidic chip according to claim 1, wherein: the PDMS mixed material is prepared by uniformly mixing a curing agent, a coagent and PDMS before paraffin is molded, and vacuumizing to remove bubbles; after the PDMS material is molded, vacuumizing again to remove bubbles, and standing for curing; the standing time is more than 24 hours.
CN202311516236.6A 2023-11-15 2023-11-15 Method for manufacturing PDMS micro-fluidic chip Active CN117244599B (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1477054A (en) * 2002-05-15 2004-02-25 Microstructure manufacture and microsystem integration
CN1700011A (en) * 2004-05-21 2005-11-23 中国科学院生态环境研究中心 Process for preparing polymer microfluidic chips
CN112473756A (en) * 2020-11-06 2021-03-12 重庆工程职业技术学院 Method for processing PDMS micro-fluidic chip
CN113877642A (en) * 2021-08-24 2022-01-04 杭州电子科技大学 Paper-based micro-channel sweat flow monitoring chip structure and preparation method thereof
CN114544574A (en) * 2022-02-24 2022-05-27 江苏大学 Method for detecting organophosphorus pesticide by using micro-fluidic chip based on fluorescent sensing film
CN115740487A (en) * 2022-11-10 2023-03-07 浙江闪铸三维科技有限公司 Method for multi-jet 3D printing of component with complex inner cavity structure
CN116002612A (en) * 2023-01-11 2023-04-25 中国科学技术大学苏州高等研究院 PMMA micro-fluidic chip packaging method and PMMA micro-fluidic chip

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20110995A1 (en) * 2011-05-31 2012-12-01 Ione METHOD FOR THE PRODUCTION OF MONOLITHIC THREE-DIMENSIONAL MICROFLUID DEVICES

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1477054A (en) * 2002-05-15 2004-02-25 Microstructure manufacture and microsystem integration
CN1700011A (en) * 2004-05-21 2005-11-23 中国科学院生态环境研究中心 Process for preparing polymer microfluidic chips
CN112473756A (en) * 2020-11-06 2021-03-12 重庆工程职业技术学院 Method for processing PDMS micro-fluidic chip
CN113877642A (en) * 2021-08-24 2022-01-04 杭州电子科技大学 Paper-based micro-channel sweat flow monitoring chip structure and preparation method thereof
CN114544574A (en) * 2022-02-24 2022-05-27 江苏大学 Method for detecting organophosphorus pesticide by using micro-fluidic chip based on fluorescent sensing film
CN115740487A (en) * 2022-11-10 2023-03-07 浙江闪铸三维科技有限公司 Method for multi-jet 3D printing of component with complex inner cavity structure
CN116002612A (en) * 2023-01-11 2023-04-25 中国科学技术大学苏州高等研究院 PMMA micro-fluidic chip packaging method and PMMA micro-fluidic chip

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