CN113893889A - Method for sealing micro-fluidic chip - Google Patents
Method for sealing micro-fluidic chip Download PDFInfo
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- CN113893889A CN113893889A CN202010639015.8A CN202010639015A CN113893889A CN 113893889 A CN113893889 A CN 113893889A CN 202010639015 A CN202010639015 A CN 202010639015A CN 113893889 A CN113893889 A CN 113893889A
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- microfluidic chip
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- microfluidic
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- 238000000034 method Methods 0.000 title claims abstract description 44
- 238000007789 sealing Methods 0.000 title claims abstract description 29
- 239000000463 material Substances 0.000 claims description 14
- 239000011347 resin Substances 0.000 claims description 13
- 229920005989 resin Polymers 0.000 claims description 13
- 238000000016 photochemical curing Methods 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 12
- 238000005516 engineering process Methods 0.000 claims description 9
- 238000012545 processing Methods 0.000 claims description 8
- 239000004115 Sodium Silicate Substances 0.000 claims description 7
- 238000011049 filling Methods 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 claims description 7
- 229910052911 sodium silicate Inorganic materials 0.000 claims description 7
- 239000000654 additive Substances 0.000 claims description 6
- 230000000996 additive effect Effects 0.000 claims description 6
- 238000004140 cleaning Methods 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 2
- 238000001723 curing Methods 0.000 claims description 2
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 2
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 2
- 239000012153 distilled water Substances 0.000 claims description 2
- 239000011521 glass Substances 0.000 claims description 2
- 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 description 2
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 claims description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 4
- 238000002347 injection Methods 0.000 claims 2
- 239000007924 injection Substances 0.000 claims 2
- 239000003960 organic solvent Substances 0.000 claims 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims 1
- 239000000945 filler Substances 0.000 claims 1
- 229920002674 hyaluronan Polymers 0.000 claims 1
- 229960003160 hyaluronic acid Drugs 0.000 claims 1
- 238000002844 melting Methods 0.000 claims 1
- 230000008018 melting Effects 0.000 claims 1
- 239000012188 paraffin wax Substances 0.000 claims 1
- 229910052710 silicon Inorganic materials 0.000 claims 1
- 239000010703 silicon Substances 0.000 claims 1
- 239000001993 wax Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 5
- 238000010586 diagram Methods 0.000 description 8
- 239000007788 liquid Substances 0.000 description 7
- 238000001746 injection moulding Methods 0.000 description 3
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 2
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 2
- 239000010408 film Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000007639 printing Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000013039 cover film Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000009499 grossing Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
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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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0887—Laminated structure
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/12—Specific details about materials
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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)
- Physical Or Chemical Processes And Apparatus (AREA)
- Micromachines (AREA)
Abstract
The invention relates to a sealing method of a microfluidic chip, belonging to the technical field of preparation of biochemical instrument equipment. The sealing method of the microfluidic chip provided by the embodiment of the invention is simple and easy to implement, can efficiently realize the sealing of the microfluidic chip, and greatly reduces the preparation cost of the microfluidic chip.
Description
Technical Field
The invention belongs to the technical field of biochemical instrument equipment preparation, and particularly relates to a method for sealing a micro-channel in a micro-fluidic chip.
Background
Microfluidics is a technology for controlling the flow of microfluidics on a small scale, and can concentrate a series of processes involved in various disciplines, such as sample preparation, chemical reaction and separation, onto a chip which is only a few square centimeters or even smaller. Because the micro-fluidic chip utilizes the flowing property of fluid under the micro-scale to carry out various operations, and uses various operation technologies to control the fluid to flow in a network formed by micro-channels in the chip, a sample is in the conditions of laminar flow and low Reynolds number when flowing in the chip, and the purpose of accurately controlling the sample is achieved. Therefore, precise formation of microchannels in microfluidic chips is of great importance.
The processing and forming of the flow channel in the microfluidic chip are difficult because the flow channel is too tiny. The microfluidic chip can be made of PDMS, resin, glass, silicon chips and other materials, the processing mode is mostly an injection molding mode, and the method can be used for large-scale production but has lower precision.
Since the height and depth of the micro flow channel holes are too small, it is difficult to control the precision of the micro flow channel holes during processing. And the material has certain deflection after processing, especially because the micro-channel chip requires high precision, the micro deflection can cause the micro-channel in the chip to deform and the pore diameter of the micro-channel to be uneven, even to be blocked, thereby affecting the use effect. And the deformation of the surface of the microfluidic chip after processing can affect the bonding process between the rear plate and the front plate. Therefore, a method of processing a micro flow channel with high accuracy and with certainty is required.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a method for sealing a microfluidic chip to solve the problems of low preparation precision and high difficulty of a microchannel.
The method of the invention is realized by the following technical scheme.
A method for sealing the channel of microfluidic chip by photocuring method is basically implemented as follows
The method comprises the following steps: filling or covering the microchannel and the sample inlet in the unsealed microfluidic chip;
step two: preparing a cover plate on the surface of the filled or covered microfluidic chip by a photocuring additive manufacturing technology to realize sealing of the chip;
step three: removing substances filled in the channel or cleaning a covering on the surface of the channel;
further, the filling material in the first step should have the following characteristics: strong binding power, higher strength, easy to be dissolved in certain liquid or easy to be volatilized under certain conditions and the like. Such as sodium silicate, solid polyethylene glycol, and the like. In the implementation process, the channel filling and the post-processing are convenient.
Further, the specific sealing method in the step two is as follows: the resin tank is filled with liquid photosensitive resin, and the liquid photosensitive resin can be rapidly cured under the irradiation of ultraviolet laser beams. When the forming process is started, the original is placed on a lifting workbench, the original is specifically positioned at the height of the thickness of one cross section layer below the liquid level, and the focused laser beam is controlled by a computer to scan along the liquid level according to the requirements of the cross section profile, so that the resin in the scanned area is cured. Thereby obtaining a resin sheet having the cross-sectional profile. The table is then lowered by the height of one sheet so that the cured resin sheet is covered with a new layer of liquid resin for a second laser shot cure, the newly cured layer being firmly bonded to the previous layer and the first layer being firmly bonded to the original, and so on until the entire product is formed. And finally, lifting the liquid resin surface out of the lifting platform, taking out the workpiece, and performing cleaning, support removal, secondary curing, surface smoothing and the like.
Furthermore, the flushing in the third step should adopt different printing modes according to different filling materials. For example, the solid polyethylene glycol and the solid sodium silicate are both easily dissolved in water, can be washed by clear water, and are repeatedly washed by adopting a heating reflux method, so that the influence on the micro-channel is avoided.
Therefore, the micro-fluidic chip is accurately sealed by using a photo-curing method.
The novel micro-channel sealing-in forming scheme effectively solves the problem that a high polymer product generated in the injection molding of the micro-flow plate is easy to deform in the traditional micro-channel forming process, and simultaneously, a grinding tool is not needed, so that the problems that the mold is difficult to process, easy to wear, inaccurate in precision control and the like in the injection molding process are solved.
The process adopts the photocuring additive manufacturing technology, the method is used for directly printing according to the designed three-dimensional drawing without a mould, and the micro-channel processing cost is lower for the production of products with small scale requirements, so that the process is a novel process which is more efficient and convenient. The material selection is more diversified, wherein the high polymer material can be used as the material of the microfluidic chip and can also be used for completing the sealing task by the photocuring additive manufacturing technology.
Drawings
Fig. 1 to 4 are schematic views of process steps specifically carried out in example 1 of the present invention, and fig. 5 to 8 are schematic views of process steps specifically carried out in example 2 of the present invention.
Fig. 1 is a schematic diagram of a microfluidic chip without sealing treatment according to the present invention.
Fig. 2 is a schematic diagram of the filled microfluidic chip of the present invention.
Fig. 3 is a schematic diagram of the sealing process performed on the filled microfluidic chip in the present invention.
Fig. 4 is a schematic diagram of the present invention showing the filling material being flushed to the sealed microfluidic chip.
Fig. 5 is a schematic diagram of a microfluidic chip without sealing treatment according to the present invention.
Fig. 6 is a schematic diagram of the covering process of the filled microfluidic chip according to the present invention.
Fig. 7 is a schematic diagram of the sealing process performed on the covered microfluidic chip according to the present invention.
Fig. 8 is a schematic diagram of the present invention showing the dissolution and washing of the cover film for the sealed microfluidic chip.
Detailed Description
The invention is further illustrated by the following specific embodiments.
The implementation scheme is as follows:
as shown in FIGS. 1 to 4, a method for sealing a microfluidic chip comprises the following steps
(1) Filling or covering the microchannel and the sample inlet in the unsealed microfluidic chip;
(2) preparing a cover plate on the surface of the filled or covered microfluidic chip by a photocuring additive manufacturing technology to realize sealing of the chip;
(3) and removing the materials filled in the channel or cleaning the surface covering of the channel.
The invention is further illustrated by the following specific examples.
Example 1
As shown in fig. 1 and 2, the microchannel 1 in the unsealed microfluidic chip is filled with solid sodium silicate 3, so that the whole microfluidic channel is filled with the solid sodium silicate, and the upper surface of the microfluidic chip is kept flat. As shown in fig. 3, a cover plate 2 is prepared on the surface of the microfluidic chip filled with the solid sodium silicate by a three-dimensional photocuring forming method, so as to realize sealing of the microfluidic chip. And finally, as shown in fig. 4, introducing distilled water into the sample inlet to flush the solid sodium silicate in the channel, and finally realizing the sealing of the microfluidic chip.
Example 2
As shown in fig. 5 and 6, a layer of film 4 is coated on the microchannel 1 in the unsealed microfluidic chip by using solid phthalic anhydride, so that the whole upper surface of the microfluidic chip is covered and the upper surface of the microfluidic chip is kept flat. As shown in fig. 7, a cover plate 2 is prepared on the surface of the microfluidic chip covered with the solid phthalic anhydride film by a three-dimensional photocuring molding method, so as to seal the microfluidic chip. Finally, as shown in fig. 8, the chip is heated to dissolve the low-melting-point thin film, and the micro-channel is flushed with a solvent to complete the sealing of the micro-fluidic chip.
Claims (11)
1. A sealing method of a microfluidic chip is characterized by comprising the following steps:
(1) filling or covering the microchannel and the sample inlet in the unsealed microfluidic chip;
(2) preparing a cover plate on the surface of the filled or covered microfluidic chip by a photocuring additive manufacturing technology to realize sealing of the chip;
(3) and removing the materials filled in the channel or cleaning the surface covering of the channel.
2. A method for sealing microfluidic chips according to claim 1, wherein the microfluidic chips made of PDMS, resin, glass, silicon wafer, etc. can be sealed.
3. A method for sealing a microfluidic chip according to claim 1, wherein the filler used to fill the microchannel and the injection port in the unsealed microfluidic chip in step (1) is selected from semi-solid organic and inorganic substances such as paraffin, hyaluronic acid wax, solid polyethylene glycol, and solid sodium silicate.
4. A method for sealing a microfluidic chip according to claim 1, wherein the material for covering the microchannel and the injection port in the unsealed microfluidic chip in step (1) is a resin film having a softening temperature lower than that of the material of the microfluidic chip.
5. The method for sealing the microfluidic chip according to claim 1, wherein the photocuring additive manufacturing technology in the step (2) can be a 3D forming technology using ultraviolet rays as curing conditions, such as Stereolithography (SLA), Digital Light Processing (DLP), LCD mask, and the like.
6. A method for sealing and sealing a microfluidic chip according to claim 1, wherein the substance filled in the channel in step (3) is removed by heating and introducing a corresponding solvent for washing, or solvent washing can be directly used.
7. A method for sealing a microfluidic chip according to claim 1, wherein the step (3) of cleaning the channel surface covering material is heating to make it adhere to the photocured covering layer or heating and introducing a solvent for washing.
8. A photocuring sealing-in method for microfluidic chips according to claim 5, wherein the optional photocuring resin is an ultraviolet-curable resin.
9. The method for removing the substance filled in the channel according to claim 6, wherein the washing solvent is an organic solvent such as methanol and ethanol or distilled water.
10. The method of claim 7, wherein the heating temperature is lower than the softening point temperature or the melting temperature of the microfluidic chip material.
11. The method for cleaning the channel surface covering material according to claim 7, wherein the washing solvent is an organic solvent such as methanol or ethanol.
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CN202010639015.8A CN113893889A (en) | 2020-07-06 | 2020-07-06 | Method for sealing micro-fluidic chip |
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CN202010639015.8A CN113893889A (en) | 2020-07-06 | 2020-07-06 | Method for sealing micro-fluidic chip |
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004205225A (en) * | 2002-12-20 | 2004-07-22 | Sumitomo Bakelite Co Ltd | Method for bonding microchip substrate and microchip |
CN101510518A (en) * | 2009-03-31 | 2009-08-19 | 中国科学院化学研究所 | Method for sealing micro-fluidic chip and use thereof |
CN102380428A (en) * | 2011-09-26 | 2012-03-21 | 复旦大学 | Solvent packaging method for polymer micro fluidic chips based on hydrogel |
CN109046479A (en) * | 2018-07-25 | 2018-12-21 | 北京化工大学 | The photocuring bonding method of micro-fluidic chip |
US20200047399A1 (en) * | 2018-08-08 | 2020-02-13 | New Jersey Institute Of Technology | Additive Manufacturing of Channels |
-
2020
- 2020-07-06 CN CN202010639015.8A patent/CN113893889A/en active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004205225A (en) * | 2002-12-20 | 2004-07-22 | Sumitomo Bakelite Co Ltd | Method for bonding microchip substrate and microchip |
CN101510518A (en) * | 2009-03-31 | 2009-08-19 | 中国科学院化学研究所 | Method for sealing micro-fluidic chip and use thereof |
CN102380428A (en) * | 2011-09-26 | 2012-03-21 | 复旦大学 | Solvent packaging method for polymer micro fluidic chips based on hydrogel |
CN109046479A (en) * | 2018-07-25 | 2018-12-21 | 北京化工大学 | The photocuring bonding method of micro-fluidic chip |
US20200047399A1 (en) * | 2018-08-08 | 2020-02-13 | New Jersey Institute Of Technology | Additive Manufacturing of Channels |
Non-Patent Citations (1)
Title |
---|
RYAN T. KELLY ET AL: "Phase-Changing Sacrificial Materials for Solvent Bonding of High-Performance Polymeric Capillary Electrophoresis Microchips", 《ANALYTICAL CHEMISTRY》 * |
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