CN119657244A - Preparation method of capillary electrophoresis micro-fluidic chip and capillary electrophoresis micro-fluidic chip - Google Patents
Preparation method of capillary electrophoresis micro-fluidic chip and capillary electrophoresis micro-fluidic chip Download PDFInfo
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- CN119657244A CN119657244A CN202411914837.7A CN202411914837A CN119657244A CN 119657244 A CN119657244 A CN 119657244A CN 202411914837 A CN202411914837 A CN 202411914837A CN 119657244 A CN119657244 A CN 119657244A
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Abstract
本发明涉及一种毛细管电泳微流控芯片制备方法及毛细管电泳微流控芯片，该制备方法包括步骤：在塑料芯片基底和/或塑料芯片盖板上成型毛细槽结构，在基底与盖板中的一个成型毛细开口；塑料芯片基底与塑料芯片盖板键合封装成塑料芯片主体，将毛细槽结构围成毛细管道，毛细管道具有2~3条进样管道臂，进样管道臂的一端连接有毛细开口，各进样管道臂的另一端形成十字或T字交叉结构；对毛细管道内壁进行表面处理；将丙烯酰胺类物质单体溶液注入毛细管道，通过将塑料芯片主体暴露于低温和保护气曝气环境下，使丙烯酰胺类物质单体溶液在毛细管道内发生原位聚合反应，形成胶体填充物；采用密封结构件对毛细开口进行封装，形成毛细管电泳微流控芯片。
The invention relates to a method for preparing a capillary electrophoresis microfluidic chip and a capillary electrophoresis microfluidic chip. The method comprises the following steps: forming a capillary groove structure on a plastic chip substrate and/or a plastic chip cover plate, and forming a capillary opening in the substrate and the cover plate; bonding and packaging the plastic chip substrate and the plastic chip cover plate into a plastic chip body, enclosing the capillary groove structure into a capillary channel, wherein the capillary channel has 2-3 injection channel arms, one end of the injection channel arm is connected with the capillary opening, and the other end of each injection channel arm forms a cross or T-shaped cross structure; surface treatment is performed on the inner wall of the capillary channel; an acrylamide substance monomer solution is injected into the capillary channel, and by exposing the plastic chip body to a low temperature and a protective gas aeration environment, the acrylamide substance monomer solution undergoes an in-situ polymerization reaction in the capillary channel to form a colloidal filler; and the capillary opening is packaged by a sealing structural member to form a capillary electrophoresis microfluidic chip.
Description
Technical Field
The invention relates to the technical field of microfluidic chips, in particular to a preparation method of a capillary electrophoresis microfluidic chip and the capillary electrophoresis microfluidic chip.
Background
Capillary electrophoresis is an analytical method based on the migration of charged particles in a solution in a capillary under the influence of an electric field. The basic principle is that the difference between the acting force of an electric field and the migration speed of charged particles in a solution is utilized to realize sample separation. Charged particles in the solution begin to migrate under the action of an electric field, and the migration speed is related to factors such as the size of the particles, the charge, the nature of the solution and the like, so that the particles are gradually separated out due to the difference. The capillary electrophoresis technology is widely applied to a plurality of fields such as biomolecule separation and enrichment, environmental pollutant analysis, clinical medicine application and the like due to the characteristics of high sensitivity, high resolution, rapidness, small sample consumption and the like.
Conventional nucleic acid capillary electrophoresis is generally performed in a glass capillary, and needle-like metal electrodes are respectively mounted at both ends of the glass capillary. During electrophoresis, a fixed-length glass capillary is filled with a colloidal screening medium (generally linear polyacrylamide) with a specific concentration, and then metal electrodes at two ends are respectively pricked into a sample solution and a buffer solution, and the sample is injected by power-on. After sampling for a period of time, the electrode needle in the sample solution is pricked into another buffer solution to complete the whole separation detection flow. In the traditional capillary electrophoresis process, the processing technology of the glass capillary is very complex, the material is high in price, and the cost is always high, so that in the actual commercial application process, the replaceable screening medium is used for electrophoresis detection. The glass capillary is used as a reusable consumable system, the glass capillary is replaced or scrapped after being used for a fixed number of times, and screening media are poured into the capillary for electrophoresis detection after pretreatment steps such as cleaning, blow-drying, surface modification and the like are needed before running electrophoresis detection each time. After each detection, the screening medium is pumped out and then the capillary electrophoresis pipeline is cleaned so as to ensure the cleaning of the interior of the capillary before the next experiment, otherwise, the secondary use of the electrophoresis pipeline is affected.
On the other hand, there is no way to pour a net-like or solid gel such as agarose or polymethylacrylamide into the capillary tube by positive or negative pressure such as injection, pouring, suction, etc., as in a liquid or gel-like gel, which greatly limits the application field of sieving the capillary tube.
Therefore, the pretreatment operation and experimental operation of the whole electrophoresis detection are very complex and complicated, the glass capillary is also very fragile, the maintenance is needed in time, the robustness of the whole system is low, and the environmental requirement is high.
Disclosure of Invention
The first object of the present invention is to provide a method for preparing a capillary electrophoresis microfluidic chip, which is to pour solid or extremely viscous gel into the capillary and store the gel in a sealed manner, simplify the pretreatment operation and experimental operation steps of electrophoresis detection, improve the robustness of the system, and reduce the cost.
The second object of the invention is to provide a capillary electrophoresis microfluidic chip based on the preparation method of the capillary electrophoresis microfluidic chip.
In order to achieve the above purpose, the present invention provides the following technical solutions:
a preparation method of a capillary electrophoresis micro-fluidic chip comprises the following steps:
forming a capillary groove structure on a plastic chip substrate and/or a plastic chip cover plate, and forming a capillary opening in the plastic chip substrate and the plastic chip cover plate;
The plastic chip substrate and the plastic chip cover plate are bonded and packaged into a plastic chip main body, the capillary groove structure is enclosed into a capillary channel, the capillary channel is provided with 2-3 sample injection channel arms, one end of each sample injection channel arm is connected with the capillary opening, and the other end of each sample injection channel arm forms a cross or T-shaped cross structure;
carrying out surface treatment on the inner wall of the capillary channel;
Injecting an acrylamide substance monomer solution into the capillary channel, and exposing the plastic chip main body to low temperature and a protective gas aeration environment to enable the acrylamide substance monomer solution to undergo an in-situ polymerization reaction in the capillary channel to form a colloid filler;
and packaging the capillary opening by adopting a sealing structural member to form the capillary electrophoresis microfluidic chip.
In one embodiment of the present application, the plastic chip substrate and the plastic chip cover plate are packaged by a thermocompression bonding process and/or a laser bonding process.
In one embodiment of the application, the in situ polymerization process is carried out in an aeration apparatus comprising:
The aeration container is provided with an air inlet and an air outlet which are used for being connected with the protection gas path system, the air inlet and the air outlet are communicated with a cavity of the aeration container, and the cavity is provided with a chip inlet and a chip outlet;
And the sealing cover plate is in sealing fit with the aeration container so as to cover the chip inlet and outlet.
In one embodiment of the application, the in situ polymerization process comprises:
the capillary openings of the plastic chip main bodies filled with the acrylamide substance monomer solution are upwards, horizontally arranged in the aeration container, and the aeration container is sealed by the sealing cover plate;
And the aeration device is connected into the protective gas circuit system, is arranged in the cold output device, adjusts the protective gas flow and pressure to be stable, and starts the in-situ polymerization reaction.
In one embodiment of the present application, the sealing structure includes a structure body, a cavity is disposed on a surface of the structure body, which is in contact with the plastic chip body, and a glue injection groove is disposed around the cavity, the cavity is configured to cover the capillary opening, and the glue injection groove is connected with a glue injection hole and a vent hole, and the glue injection hole and the vent hole extend to a surface of the structure body, which is opposite to the plastic chip body.
In one embodiment of the present application, the sealing the capillary opening with a sealing structure includes:
pressing the cavity of the sealing structure tightly against the plastic chip body in alignment with the capillary opening;
And injecting glue into the glue injection holes of the sealing structural part.
A capillary electrophoresis microfluidic chip manufactured based on the capillary electrophoresis microfluidic chip manufacturing method according to any one of the above, comprising:
The plastic chip comprises a plastic chip main body, wherein a capillary channel is arranged in the plastic chip main body, acrylamide polymer gel is stored in the capillary channel, the capillary channel is provided with 2-3 sample injection channel arms, one end of each sample injection channel arm is connected with a capillary opening, and the other end of each sample injection channel arm forms a cross or T-shaped cross structure;
and the sealing structure is adhered to the plastic chip main body in a sealing way so as to cover the capillary opening.
In one embodiment of the application, the plastic chip main body comprises a plastic chip substrate and a plastic chip cover plate, wherein a capillary groove structure is arranged on the plastic chip substrate and/or the plastic chip cover plate, one of the plastic chip substrate and the plastic chip cover plate is provided with the capillary opening, and the plastic chip substrate and the plastic chip cover plate are bonded and mutually attached to enclose the capillary groove structure into the capillary channel, and are bonded and packaged into the plastic chip main body.
In one embodiment of the present application, the sealing structure includes a structure body, a cavity is disposed on a surface of the structure body, which is in contact with the plastic chip body, and a glue injection groove is disposed around the cavity, the cavity is configured to cover the capillary opening, and the glue injection groove is connected with a glue injection hole and a vent hole, and the glue injection hole and the vent hole extend to a surface of the structure body, which is opposite to the plastic chip body.
In one embodiment of the present application, the acrylamide polymer gel is formed by cross-linking and polymerizing one or more of acrylamide, methylene acrylamide and methylene bisacrylamide, and the acrylamide polymer gel is a non-newtonian fluid or a solid.
According to the technical scheme, the preparation method of the capillary electrophoresis microfluidic chip comprises the steps of forming a capillary groove structure on a plastic chip substrate and/or a plastic chip cover plate, forming a capillary opening in the plastic chip substrate and one of the plastic chip cover plate, bonding and packaging the plastic chip substrate and the plastic chip cover plate into a plastic chip main body, enclosing the capillary groove structure into a capillary channel, wherein the capillary channel is provided with 2-3 sample channel arms, one end of each sample channel arm is connected with the capillary opening, the other end of each sample channel arm forms a cross or T-shaped cross structure, carrying out surface treatment on the inner wall of the capillary channel, injecting acrylamide monomer solution into the capillary channel, enabling the acrylamide monomer solution to undergo in-situ polymerization reaction in the capillary channel to form a colloid filler by exposing the plastic chip main body to a low-temperature protective gas aeration environment, and packaging the capillary opening by adopting a sealing structural member to form the capillary electrophoresis microfluidic chip.
According to the preparation method of the capillary electrophoresis microfluidic chip, the acrylamide monomer solution is injected into the capillary channel and polymerized in situ in the capillary channel to form the colloid filler, so that the purposes of injecting solid or extremely viscous gel into the capillary and sealing and storing the gel can be achieved, and complex pretreatment operations such as cleaning, surface coating and glue filling of the capillary electrophoresis channel are greatly simplified. The preparation method and the chip prepared by the preparation method are based on plastic materials, the cost of the chip materials is low, and meanwhile, various technological processes of preparation, molding and sealing of the electrophoresis gel are further simplified, so that the cost of the chip is greatly reduced, and the chip can be directly discarded after use. The structural design of the capillary channel is not dependent on the preparation process of gel, and the gel can be filled into the ultra-long capillary channel no matter the gel is a high-concentration viscous LPA gel or a solid-state methylene acrylamide polymer gel, so that the solid-state gel can be completely filled in the capillary channel, and the capillary electrophoresis can be suitable for richer application scenes. The preparation method is designed and constructed aiming at an automatic production line, and each process link can be automatically operated on the production line in batches, so that the production cost of the capillary electrophoresis microfluidic chip is further reduced, and the production efficiency is improved.
Drawings
In order to more clearly illustrate the embodiments of the invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, it being obvious that the drawings in the following description are only some embodiments of the invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
Fig. 1 is a flowchart of a method for preparing a capillary electrophoresis microfluidic chip according to an embodiment of the present invention;
fig. 2 is a schematic structural diagram of a plastic chip main body prepared by the capillary electrophoresis microfluidic chip preparation method according to the embodiment of the present invention;
FIG. 3 is an enlarged partial schematic view of FIG. 2 at A in one embodiment;
FIG. 4 is an enlarged partial schematic view of FIG. 2 at A in another embodiment;
fig. 5 is a cross-sectional view of an aeration device used in the preparation method of a capillary electrophoresis microfluidic chip according to the embodiment of the present invention;
Fig. 6 is a top view of an aeration device used in the preparation method of a capillary electrophoresis microfluidic chip according to the embodiment of the present invention;
Fig. 7 is a cross-sectional view of a sealing structure used in the preparation method of a capillary electrophoresis microfluidic chip according to the embodiment of the present invention when no glue is injected;
Fig. 8 is a bottom view of a sealing structure used in the preparation method of a capillary electrophoresis microfluidic chip according to the embodiment of the present invention when no glue is injected;
Fig. 9 is a cross-sectional view of a sealing structure member used in the method for manufacturing a capillary electrophoresis microfluidic chip according to the embodiment of the present invention after glue injection;
fig. 10 is a cross-sectional view of a sealing structure member used in the method for manufacturing a capillary electrophoresis microfluidic chip according to the embodiment of the present invention after glue injection;
Fig. 11 is a schematic diagram of a bonding process of a sealing structure in a preparation method of a capillary electrophoresis microfluidic chip according to an embodiment of the present invention;
Fig. 12 is a schematic partial view of a sealing structure of a capillary electrophoresis microfluidic chip produced by the method for preparing a capillary electrophoresis microfluidic chip according to the embodiment of the present invention.
Wherein:
1 is a plastic chip main body; 2 is a capillary channel, 201 is a sample feeding pipeline arm, 3 is a capillary opening, 4 is an aeration device, 401 is an aeration container, 402 is an air inlet, 403 is an air outlet, 404 is a containing cavity, 405 is a sealing cover plate, 5 is a sealing structural member, 501 is a structural member main body, 502 is a cavity, 503 is a glue injection groove, 504 is a glue injection hole, 505 is an air vent, 6 is sealing glue, 7 is acrylamide polymer gel, 8 is a pressing head, and 9 is a glue dispensing head.
Detailed Description
The invention provides a preparation method of a capillary electrophoresis microfluidic chip, which can be used for pouring solid or extremely viscous gel into a capillary tube and sealing and storing the gel, and meanwhile, the pretreatment operation and experimental operation steps of electrophoresis detection are simplified, the robustness of a system is improved, and the cost is reduced.
The invention further provides a capillary electrophoresis micro-fluidic chip based on the preparation method of the capillary electrophoresis micro-fluidic chip.
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Referring to fig. 1 to 4, fig. 1 is a flowchart of a method for preparing a capillary electrophoresis microfluidic chip according to an embodiment of the present invention, fig. 2 is a schematic structural diagram of a plastic chip main body prepared by the method for preparing a capillary electrophoresis microfluidic chip according to an embodiment of the present invention, fig. 3 is a schematic enlarged partial view at a of fig. 2 in one embodiment, and fig. 4 is a schematic enlarged partial view at a of fig. 2 in another embodiment.
The embodiment of the invention discloses a preparation method of a capillary electrophoresis micro-fluidic chip, which comprises the following steps:
The capillary groove structure is formed on the plastic chip substrate and/or the plastic chip cover plate, and the capillary opening 3 is formed in the plastic chip substrate and the plastic chip cover plate.
The chip is prepared by adopting plastics, the plastic materials comprise but are not limited to cycloolefin polymer plastic (COP plastic) and polycarbonate plastic (PC plastic), in the actual preparation process, the capillary groove structure can be formed on one of the plastic chip substrate and the plastic chip cover plate, the other of the plastic chip substrate and the plastic chip cover plate is not processed, the plastic chip substrate and the plastic chip cover plate is a smooth surface structure, the capillary groove structure with corresponding shapes can be formed on the plastic chip substrate and the plastic chip cover plate at the same time, the capillary groove structure of the plastic chip substrate and the capillary groove structure of the plastic chip cover plate are mutually matched to form the capillary channel 2, the capillary opening 3 can be arranged on one of the plastic chip substrate and the plastic chip cover plate, which is not processed, as long as the capillary opening 3 corresponds to the inlet position of the capillary groove structure on the other of the plastic chip substrate and the plastic chip cover plate, or the capillary groove structure and the capillary opening 3 can be processed on the same chip component, and the cross section area of the capillary channel 2 is preferably between 3×10 2μm2~3×104μm2 in one embodiment of the application. The plastic chip substrate and the plastic chip cover plate are bonded and packaged into a plastic chip main body 1, the capillary groove structure is enclosed into a capillary channel 2, the capillary channel 2 is provided with 2-3 sample injection channel arms 201, one end of each sample injection channel arm 201 is connected with a capillary opening 3, and the other end of each sample injection channel arm 201 forms a cross or T-shaped cross structure.
It should be noted that, the shape of the plastic chip main body 1 is square or rectangular, and the capillary channel 2 on the plastic chip main body must have 2-3 sample channel arms 201 with cross or T-shaped cross structures, as shown in fig. 3, when the capillary channel 2 has 2 sample channel arms 201, the T-shaped cross structures are formed between the 2 sample channel arms 201 and the main pipe of the capillary channel 2, as shown in fig. 4, when the capillary channel 2 has 3 sample channel arms 201, the cross structures are formed between the 3 sample channel arms 201 and the main pipe of the capillary channel 2, and then the processing, production and preparation can be performed by adopting the process method described in the present application.
The inner wall of the capillary channel 2 is surface treated.
The surface treatment steps are not exactly the same, depending on the type of plastic, and in general, the surface treatment includes surface cleaning and chemical modification, although some types of plastic only require surface cleaning and no chemical modification.
The acrylamide monomer solution is injected into the capillary channel 2, and the plastic chip main body 1 is exposed to low temperature and protective gas aeration environment, so that the acrylamide monomer solution is subjected to in-situ polymerization reaction in the capillary channel 2 to form the colloid filler.
The colloid filler formed by the in-situ polymerization reaction is acrylamide polymer gel such as linear polyacrylamide, methylene acrylamide and the like, and can be polymerized by using various modes such as chemical initiation, photoinitiation and the like.
The preparation method in the embodiment of the application is only aimed at acrylamide gel, and the acrylamide polymerization reaction is an anaerobic reaction, so that air needs to be removed, and therefore, the plastic chip main body 1 needs to be protected by using a shielding gas for aeration in the polymerization process.
And packaging the capillary opening 3 by adopting a sealing structural member 5 to form the capillary electrophoresis microfluidic chip.
The sealing structure 5 is preferably made of the same material as the plastic chip main body 1, and is mainly used for sealing and adhering to the capillary opening 3 of the plastic chip main body 1 to form a complete seal, so that the acrylamide gel can be stored in the capillary channel 2 for a long time.
Compared with the prior art, the preparation method of the capillary electrophoresis microfluidic chip provided by the embodiment of the invention has the advantages that the acrylamide substance monomer solution is injected into the capillary channel 2 and is polymerized in situ in the capillary channel 2 to form the colloid filler, so that the purposes of injecting solid or extremely viscous gel into the capillary and performing sealed storage can be achieved, and complex pretreatment operations such as cleaning, surface coating and glue filling of the capillary electrophoresis channel are greatly simplified. The preparation method and the chip prepared by the preparation method are based on plastic materials, the cost of the chip materials is low, and meanwhile, various technological processes of preparation, molding and sealing of the electrophoresis gel are further simplified, so that the cost of the chip is greatly reduced, and the chip can be directly discarded after use. The structural design of the capillary channel 2 is not dependent on the preparation process of gel, and the gel can be filled into the overlength capillary channel 2 no matter the gel is a high-concentration viscous LPA gel or a solid state methylene acrylamide polymer gel, so that the complete filling of the solid state gel in the capillary channel 2 is realized, and the capillary electrophoresis can be suitable for richer application scenes. The preparation method is designed and constructed aiming at an automatic production line, and each process link can be automatically operated on the production line in batches, so that the production cost of the capillary electrophoresis microfluidic chip is further reduced, and the production efficiency is improved.
Specifically, in one embodiment of the present application, the capillary groove structure and the capillary opening 3 are formed on the plastic chip substrate or the plastic chip cover plate by an embossing or injection molding process. It is of course understood that the above-mentioned molding mode of the capillary groove structure and the capillary opening 3 and the packaging mode of the plastic chip body 1 are merely preferred embodiments provided by the embodiments of the present application, and are not limited to the above-mentioned embodiments, and those skilled in the art can select a suitable mode to realize molding and packaging according to the needs.
Specifically, in the above-mentioned method of preparation, the surface treatment of the inner wall of the capillary channel 2 comprises:
the surface treatment process is determined according to the material of the plastic chip main body 1, wherein the surface treatment process is that the cleaning solvent cleans the inner wall of the capillary channel 2, or the surface treatment process is that the chemical modification solvent is adopted to coat the inner wall of the capillary channel 2 after the cleaning solvent cleans the inner wall of the capillary channel 2.
For different types of plastics, the difference of the surface treatment process is large, and taking COP plastics as an example, the plastics do not need to be subjected to chemical modification, only the surface of the capillary channel 2 is required to be cleaned, ethanol, water and other solvents can be used for repeatedly cleaning the capillary channel 2, the electric neutral surface can be obtained after the liquid is pumped out, the PC plastics need to be subjected to chemical modification, ethanol, water and other solvents are required to be used for repeatedly cleaning the capillary channel 2, and the DEH solvent is used for coating the inner wall of the capillary channel 2 after the liquid is pumped out.
And adopting a determined surface treatment process to carry out surface treatment on the inner wall of the capillary channel 2.
After the surface treatment process is determined, the inner wall of the capillary channel 2 is subjected to surface treatment according to the surface treatment process.
In order to ensure smooth in-situ polymerization, the embodiment of the application provides a device specially used for aeration of shielding gas, and the in-situ polymerization process is carried out in the aeration device 4, as shown in fig. 5 and 6, the aeration device 4 comprises an aeration container 401 and a sealing cover plate 405, wherein the aeration container 401 is provided with an air inlet 402 and an air outlet 403 for accessing a shielding gas path system, the air inlet 402 and the air outlet 403 are communicated with a cavity 404 of the aeration container 401, the cavity 404 is provided with a chip inlet and a chip outlet, and the sealing cover plate 405 is in sealing fit with the aeration container 401 so as to cover the chip inlet and the chip outlet.
In a specific embodiment of the present application, the cavity 404 of the aeration container 401 is a ship shape, the bottom of the cavity 404 is a relatively wide plane, the capillary openings 3 of the plastic chip main body 1 filled with the acrylamide monomer solution are upwards, and the plastic chip main body is horizontally placed on the plane of the bottom of the container side by side, and the protective gas is introduced from the air inlet 402, and is constant-current and constant-pressure under the action of the internal structure of the aeration container 401 to the air outlet 403 on the other side so as to discharge air, so that the upper part of the plastic chip main body 1 is completely covered by the protective gas, and meanwhile, the polymerization process is also required to be performed at a low temperature, so that the aeration container 401 is made of a thermal good conductor material, such as stainless steel or aluminum alloy, and the sealing cover plate 405 is made of a transparent material, such as glass or acrylic material, and a sealing ring is arranged between the sealing cover plate 405 and the aeration container 401 so as to seal.
Based on the aeration device 4 described above, in one embodiment of the present application, the in-situ polymerization process comprises:
A plurality of plastic chip bodies 1 filled with acrylamide monomer solution are placed in an aeration container 401, capillary openings 3 of the plastic chip bodies 1 are horizontally placed side by side upwards, and after the plastic chip bodies 1 are placed in the aeration container 401, a sealing cover plate 405 is used for sealing the aeration container 401 to form a sealed aeration space.
The aeration device 4 is connected into a protective gas circuit system through the gas inlets 402 and the gas outlets 403 at two ends, protective gas is introduced into the cavity 404 of the aeration container 401, and the aeration device 4 is arranged in a cold output device, and the cold output device can be a refrigerator, an ice box and the like, and can also realize the temperature control of the environment where the plastic chip main body 1 is positioned by controlling the temperature of the protective gas, adjust the protective gas flow and pressure to be stable and start in-situ polymerization reaction.
As shown in fig. 7 and 8, in one embodiment of the present application, the sealing structure 5 includes a structure body 501, a cavity 502 is disposed on a surface of the structure body 501 for contacting the plastic chip body 1, and a glue injection groove 503 is disposed around the cavity 502, the cavity 502 is configured to cover the capillary opening 3, the glue injection groove 503 is connected with a glue injection hole 504 and a vent hole 505, and the glue injection hole 504 and the vent hole 505 extend to a surface of the structure body 501 facing away from the plastic chip body 1.
When bonding the sealing structure 5 to the plastic chip body 1, as shown in fig. 9 and 10, the sealant 6 is injected into the sealant injection hole 504, the sealant 6 enters the sealant injection groove 503 from the sealant injection hole 504, and gradually fills the sealant injection groove 503, and simultaneously, the gas in the sealing structure 5 is discharged from the vent hole 505, and when the sealant 6 is observed in the vent hole 505, the completion of the filling of the sealant 6 is indicated.
Based on the sealing structure 5, in an embodiment of the present application, the sealing structure 5 is used to encapsulate the capillary opening 3, which includes:
the cavity 502 of the sealing structure 5 is pressed tightly against the plastic chip body 1 in alignment with the capillary opening 3.
This step is achieved by means of a pressing mechanism adapted to the sealing structure 5, the pressing mechanism having a pressing head 8, the pressing head 8 being made of polytetrafluoroethylene, and being provided with a glue injection port and a vent port corresponding to the glue injection hole 504 and the vent hole 505 of the sealing structure 5, respectively.
Glue is injected into the glue injection holes 504 of the sealing structure 5.
As shown in fig. 11, the pressing head 8 presses the sealing structure 5 on the to-be-bonded position of the plastic chip main body 1 from above, so that the pressing head 8 is relatively fixed with the plastic chip main body 1, the dispensing head 9 of the sealing glue 6 is pressed against the dispensing hole 504 of the sealing structure 5 from the passing dispensing opening of the pressing head 8, the dispensing and dispensing operations of the sealing glue 6 are performed, after the dispensing operation of the sealing glue 6 is completed, the dispensing head 9 is lifted, and then the pressing head 8 is lifted, so that the whole packaging process of the capillary electrophoresis micro-fluidic chip is completed, as shown in fig. 12.
It should be noted that, in order to ensure the adhesion effect between the sealing structure 5 and the plastic chip body 1, in an embodiment of the present application, before the sealing structure 5 is used to encapsulate the capillary opening 3, the excess acrylamide polymer gel 7 at the capillary opening 3 is removed, so as to avoid that the acrylamide polymer gel 7 overflowed from the capillary channel 2 during the in-situ polymerization process affects the adhesion effect between the sealing structure 5 and the plastic chip body 1.
The embodiment of the application also provides a capillary electrophoresis microfluidic chip manufactured based on the capillary electrophoresis microfluidic chip manufacturing method, which is characterized in that the capillary electrophoresis microfluidic chip comprises a plastic chip main body 1 and a sealing structural member 5, wherein the plastic chip main body 1 comprises, but is not limited to, COP plastic and PC plastic, a capillary channel 2 is arranged in the plastic chip main body 1, an acrylamide polymer gel 7 is stored in the capillary channel 2, the capillary channel 2 is provided with 2-3 sample-taking channel arms 201, one end of each sample-taking channel arm 201 is connected with a capillary opening 3, the other end of each sample-taking channel arm 201 forms a cross or T-shaped cross structure, the sealing structural member 5 is sealed and adhered to the plastic chip main body 1 to cover the capillary opening 3, the capillary electrophoresis microfluidic chip is manufactured by plastic, and various processes of gel electrophoresis preparation, molding and sealing are further simplified while the cost of the chip is greatly reduced, and the chip can be directly discarded after being used. Meanwhile, the acrylamide polymer gel 7 is directly stored in the capillary channel 2, so that complex pretreatment operations such as cleaning, surface coating and glue filling of the capillary electrophoresis channel are greatly simplified.
Further optimizing the above technical scheme, in a specific embodiment, the plastic chip main body 1 comprises a plastic chip substrate and a plastic chip cover plate, a capillary groove structure is arranged on the plastic chip substrate and/or the plastic chip cover plate, one of the plastic chip substrate and the plastic chip cover plate is provided with a capillary opening 3, and the plastic chip substrate and the plastic chip cover plate are bonded and mutually attached to enclose the capillary groove structure into a capillary channel 2, and are bonded and packaged into the plastic chip main body 1.
As shown in fig. 7, 8 and 12, in one embodiment of the present application, the sealing structure 5 includes a structure body 501, a cavity 502 is disposed on a surface of the structure body 501, which is used for contacting with the plastic chip body 1, and a glue injection groove 503 disposed around the cavity 502, the cavity 502 is used for covering the capillary opening 3, the glue injection groove 503 is connected with a glue injection hole 504 and a vent hole 505, and the glue injection hole 504 and the vent hole 505 extend to a surface of the structure body 501, which is opposite to the plastic chip body 1.
In the present application, the acrylamide polymer gel 7 is formed by cross-linking and polymerizing one or more of acrylamide, methylene acrylamide and methylene bisacrylamide, and the acrylamide polymer gel 7 is a non-newtonian fluid or a solid, and it should be noted that acrylamide, methylene acrylamide and methylene bisacrylamide are only preferred embodiments provided in the embodiments of the present application, and in practice, the present application is not limited to these three types of acrylamide polymer gels, and other acrylamide materials may be used.
In the present specification, each embodiment is described in a progressive manner, and each embodiment is mainly described in a different point from other embodiments, and identical and similar parts between the embodiments are all enough to refer to each other.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (10)
1. The preparation method of the capillary electrophoresis micro-fluidic chip is characterized by comprising the following steps:
forming a capillary groove structure on a plastic chip substrate and/or a plastic chip cover plate, and forming a capillary opening in the plastic chip substrate and the plastic chip cover plate;
The plastic chip substrate and the plastic chip cover plate are bonded and packaged into a plastic chip main body, the capillary groove structure is enclosed into a capillary channel, the capillary channel is provided with 2-3 sample injection channel arms, one end of each sample injection channel arm is connected with the capillary opening, and the other end of each sample injection channel arm forms a cross or T-shaped cross structure;
carrying out surface treatment on the inner wall of the capillary channel;
Injecting an acrylamide substance monomer solution into the capillary channel, and exposing the plastic chip main body to low temperature and a protective gas aeration environment to enable the acrylamide substance monomer solution to undergo an in-situ polymerization reaction in the capillary channel to form a colloid filler;
and packaging the capillary opening by adopting a sealing structural member to form the capillary electrophoresis microfluidic chip.
2. The method for preparing a capillary electrophoresis microfluidic chip according to claim 1, wherein said plastic chip substrate and said plastic chip cover plate are packaged by a thermocompression bonding process and/or a laser bonding process.
3. The method for preparing a capillary electrophoresis microfluidic chip according to claim 1, wherein said in situ polymerization process is performed in an aeration device comprising:
The aeration container is provided with an air inlet and an air outlet which are used for being connected with the protection gas path system, the air inlet and the air outlet are communicated with a cavity of the aeration container, and the cavity is provided with a chip inlet and a chip outlet;
And the sealing cover plate is in sealing fit with the aeration container so as to cover the chip inlet and outlet.
4. The method for preparing a capillary electrophoresis microfluidic chip according to claim 3, wherein said in situ polymerization process comprises:
the capillary openings of the plastic chip main bodies filled with the acrylamide substance monomer solution are upwards, horizontally arranged in the aeration container, and the aeration container is sealed by the sealing cover plate;
And the aeration device is connected into the protective gas circuit system, is arranged in the cold output device, adjusts the protective gas flow and pressure to be stable, and starts the in-situ polymerization reaction.
5. The method for preparing a capillary electrophoresis microfluidic chip according to claim 1, wherein said sealing structure comprises a structure body, a cavity and a glue injection groove are arranged on the surface of said structure body, said surface is in contact with said plastic chip body, said cavity is used for covering said capillary opening, said glue injection groove is connected with a glue injection hole and a vent hole, and said glue injection hole and said vent hole extend to the surface of said structure body, said surface being opposite to said plastic chip body.
6. The method of manufacturing a capillary electrophoresis microfluidic chip according to claim 5, wherein said encapsulating said capillary openings with sealing structures comprises:
pressing the cavity of the sealing structure tightly against the plastic chip body in alignment with the capillary opening;
And injecting glue into the glue injection holes of the sealing structural part.
7. A capillary electrophoresis microfluidic chip manufactured based on the method for manufacturing a capillary electrophoresis microfluidic chip according to any one of claims 1-6, comprising:
The plastic chip comprises a plastic chip main body, wherein a capillary channel is arranged in the plastic chip main body, acrylamide polymer gel is stored in the capillary channel, the capillary channel is provided with 2-3 sample injection channel arms, one end of each sample injection channel arm is connected with a capillary opening, and the other end of each sample injection channel arm forms a cross or T-shaped cross structure;
and the sealing structure is adhered to the plastic chip main body in a sealing way so as to cover the capillary opening.
8. The capillary electrophoresis microfluidic chip according to claim 7, wherein the plastic chip main body comprises a plastic chip substrate and a plastic chip cover plate, a capillary groove structure is arranged on the plastic chip substrate and/or the plastic chip cover plate, the capillary opening is arranged on one of the plastic chip substrate and the plastic chip cover plate, the plastic chip substrate and the plastic chip cover plate are bonded and mutually attached to enclose the capillary groove structure into the capillary channel, and the capillary channel structure is bonded and packaged into the plastic chip main body.
9. The capillary electrophoresis microfluidic chip according to claim 7, wherein said sealing structure comprises a structure body, a cavity is arranged on a surface of said structure body, which is used for contacting with said plastic chip body, and a glue injection groove is arranged around said cavity, said cavity is used for covering said capillary opening, said glue injection groove is connected with a glue injection hole and a vent hole, and said glue injection hole and said vent hole extend to a surface of said structure body, which is opposite to said plastic chip body.
10. The capillary electrophoresis microfluidic chip according to claim 7, wherein said acrylamide polymer gel is formed by cross-linking polymerization of one or more of acrylamide, methylene acrylamide and methylene bisacrylamide, and said acrylamide polymer gel is a non-newtonian fluid or solid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411914837.7A CN119657244A (en) | 2024-12-24 | 2024-12-24 | Preparation method of capillary electrophoresis micro-fluidic chip and capillary electrophoresis micro-fluidic chip |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411914837.7A CN119657244A (en) | 2024-12-24 | 2024-12-24 | Preparation method of capillary electrophoresis micro-fluidic chip and capillary electrophoresis micro-fluidic chip |
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| Publication Number | Publication Date |
|---|---|
| CN119657244A true CN119657244A (en) | 2025-03-21 |
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|---|---|---|---|
| CN202411914837.7A Pending CN119657244A (en) | 2024-12-24 | 2024-12-24 | Preparation method of capillary electrophoresis micro-fluidic chip and capillary electrophoresis micro-fluidic chip |
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| Country | Link |
|---|---|
| CN (1) | CN119657244A (en) |
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2024
- 2024-12-24 CN CN202411914837.7A patent/CN119657244A/en active Pending
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