Capillary electrophoresis microfluidic chip preparation method and capillary electrophoresis microfluidic chip

Abstract

The invention relates to a method for preparing a capillary electrophoresis microfluidic chip and the 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 encapsulating 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 sampling channel arms, one end of the sampling channel arm is connected to the capillary opening, and the other end of each sampling channel arm forms a cross or T-shaped cross structure; surface treating the inner wall of the capillary channel; injecting an acrylamide monomer solution into the capillary channel, exposing the plastic chip body to a low temperature and protective gas aeration environment, causing the acrylamide monomer solution to undergo an in-situ polymerization reaction in the capillary channel to form a colloidal filler; and encapsulating the capillary opening with a sealing structure to form the capillary electrophoresis microfluidic chip.

Description

Technical Field

[0001] The present invention relates to the technical field of microfluidic chips, and in particular to a method for preparing a capillary electrophoresis microfluidic chip and the capillary electrophoresis microfluidic chip. Background Art

[0002] Capillary electrophoresis is an analytical method based on the migration of charged particles in a solution through a capillary tube under the influence of an electric field. Its basic principle is to separate samples by exploiting the difference between the force of the electric field and the migration speed of the charged particles in the solution. Charged particles in the solution begin to migrate under the influence of the electric field, and their migration speed is related to factors such as particle size, charge, and the properties of the solution. These differences gradually separate them. Due to its high sensitivity, high resolution, rapid speed, and low sample consumption, capillary electrophoresis is widely used in a variety of fields, including the separation and enrichment of biomolecules, the analysis of environmental pollutants, and clinical applications.

[0003] Traditional nucleic acid capillary electrophoresis is typically performed in glass capillaries with needle-shaped metal electrodes mounted at each end. During electrophoresis, a fixed-length glass capillary is first filled with a colloidal sieving medium (typically linear polyacrylamide) at a specific concentration. The metal electrodes at each end are then inserted into the sample solution and buffer solution, respectively, and a voltage is applied for sample injection. After a period of injection, the electrode needles in the sample solution are inserted into another buffer solution to complete the separation and detection process. Traditional capillary electrophoresis is complex in its processing and the material itself is expensive, resulting in high costs. Therefore, in commercial applications, replaceable sieving media are used for electrophoretic detection. These reusable glass capillaries are used as consumables and are replaced or discarded after a fixed number of uses. Each electrophoretic run requires pretreatment steps such as cleaning, drying, and surface modification before the sieving media is injected into the capillary for electrophoretic detection. After each test is completed, the sieving medium needs to be extracted and the capillary electrophoresis tube needs to be cleaned to ensure the cleanliness of the capillary before the next round of experiments, otherwise it will affect the secondary use of the electrophoresis tube.

[0004] On the other hand, for reticular and solid gels such as agarose and poly(methylene acrylamide), there is no way to infuse them into the capillary through positive or negative pressure methods such as injection, perfusion, and suction like liquid or colloidal gels, which greatly limits the screening application scenarios of the capillary.

[0005] Therefore, the pre-treatment and experimental operations of the entire electrophoresis detection are very complex and tedious. The glass capillaries are also very fragile and require timely maintenance. The robustness of the entire system is low and the environmental requirements are high. Summary of the Invention

[0006] The first object of the present invention is to provide a method for preparing a capillary electrophoresis microfluidic chip, so as to inject a solid or extremely viscous gel into the interior of the capillary and store it in a sealed manner, while simplifying the pre-treatment operations and experimental operation steps of electrophoresis detection, improving the robustness of the system and reducing costs.

[0007] The second object of the present invention is to provide a capillary electrophoresis microfluidic chip based on the above-mentioned capillary electrophoresis microfluidic chip preparation method.

[0008] To achieve the above object, the present invention provides the following technical solutions:

[0009] A method for preparing a capillary electrophoresis microfluidic chip comprises the following steps:

[0010] forming a capillary groove structure on a plastic chip substrate and / or a plastic chip cover, and forming a capillary opening in one of the plastic chip substrate and the plastic chip cover;

[0011] The plastic chip base and the plastic chip cover are bonded and packaged into a plastic chip body, and the capillary groove structure is surrounded by a capillary channel, wherein the capillary channel has 2 to 3 sampling channel arms, one end of each sampling channel arm is connected to the capillary opening, and the other end of each sampling channel arm forms a cross or T-shaped cross structure;

[0012] performing surface treatment on the inner wall of the capillary channel;

[0013] injecting an acrylamide monomer solution into the capillary channel, and exposing the plastic chip body to a low temperature and protective gas aeration environment to cause the acrylamide monomer solution to undergo an in-situ polymerization reaction in the capillary channel to form a colloidal filler;

[0014] The capillary opening is packaged with a sealing structure to form a capillary electrophoresis microfluidic chip.

[0015] In one embodiment of the present application, the plastic chip substrate and the plastic chip cover are packaged by a thermocompression bonding process and / or a laser bonding process.

[0016] In one embodiment of the present application, the in-situ polymerization process is carried out in an aeration device, and the aeration device comprises:

[0017] An aeration container, the aeration container having an air inlet and an air outlet for accessing a protective gas circuit system, the air inlet and the air outlet being in communication with a cavity of the aeration container, the cavity having a chip inlet and outlet;

[0018] A sealing cover plate is sealed and matched with the aeration container to cover the chip inlet and outlet.

[0019] In one embodiment of the present application, the in-situ polymerization process includes:

[0020] Placing a plurality of plastic chip bodies filled with acrylamide monomer solution with the capillary openings facing upwards, horizontally and side by side in the aeration container, and sealing the aeration container with the sealing cover plate;

[0021] The aeration device is connected to the protective gas gas circuit system, and the aeration device is placed in the cold output device, and the protective gas flow and pressure are adjusted to be stable, and the in-situ polymerization reaction is started.

[0022] In one embodiment of the present application, the sealing structural component includes a structural component body, the surface of the structural component body being used to be in contact with the plastic chip body is provided with a cavity and a glue injection groove provided around the cavity, the cavity is used to cover the capillary opening, the glue injection groove is connected with a glue injection hole and an exhaust hole, and the glue injection hole and the exhaust hole extend to the surface of the structural component body facing away from the plastic chip body.

[0023] In one embodiment of the present application, the encapsulating the capillary opening with a sealing structure includes:

[0024] Aligning the cavity of the sealing structure with the capillary opening and pressing it tightly against the plastic chip body;

[0025] Glue is injected into the glue injection hole of the sealing structural component.

[0026] A capillary electrophoresis microfluidic chip manufactured based on the capillary electrophoresis microfluidic chip preparation method described in any one of the above, comprising:

[0027] A plastic chip body having a capillary channel within the plastic chip body, wherein the capillary channel stores an acrylamide polymer gel, the capillary channel having 2 to 3 injection channel arms, one end of each injection channel arm being connected to a capillary opening, and the other end of each injection channel arm forming a cross or T-shaped cross structure;

[0028] A sealing structure is sealed and bonded to the plastic chip body to cover the capillary opening.

[0029] In one embodiment of the present application, the plastic chip body includes a plastic chip base and a plastic chip cover plate, and a capillary groove structure is provided on the plastic chip base and / or the plastic chip cover plate. The capillary opening is provided on one of the plastic chip base and the plastic chip cover plate, and the plastic chip base and the plastic chip cover plate are bonded and adhered to each other to enclose the capillary groove structure into the capillary channel, and are bonded and packaged into the plastic chip body.

[0030] In one embodiment of the present application, the sealing structural component includes a structural component body, the surface of the structural component body being used to be in contact with the plastic chip body is provided with a cavity and a glue injection groove provided around the cavity, the cavity is used to cover the capillary opening, the glue injection groove is connected with a glue injection hole and an exhaust hole, and the glue injection hole and the exhaust hole extend to the surface of the structural component body facing away from the plastic chip body.

[0031] In one embodiment of the present application, the acrylamide polymer gel is formed by cross-linking and polymerization of one or more combinations of acrylamide, methylene acrylamide, and methylene bisacrylamide, and the acrylamide polymer gel is a non-Newtonian fluid or a solid.

[0032] As can be seen from the above technical solution, the present invention discloses a method for preparing a capillary electrophoresis microfluidic chip, which includes the following steps: forming a capillary groove structure on a plastic chip substrate and / or a plastic chip cover, and forming a capillary opening in the plastic chip substrate and the plastic chip cover; bonding and encapsulating the plastic chip substrate and the plastic chip cover into a plastic chip body, enclosing the capillary groove structure into a capillary channel, wherein the capillary channel has 2 to 3 sampling channel arms, one end of the sampling channel arm is connected to the capillary opening, and the other end of each sampling channel arm forms a cross or T-shaped cross structure; surface treating the inner wall of the capillary channel; injecting an acrylamide monomer solution into the capillary channel, and exposing the plastic chip body to a low temperature and protective gas aeration environment to cause the acrylamide monomer solution to undergo an in-situ polymerization reaction in the capillary channel to form a colloidal filler; and encapsulating the capillary opening with a sealing structure to form a capillary electrophoresis microfluidic chip.

[0033] The above-mentioned capillary electrophoresis microfluidic chip preparation method injects an acrylamide monomer solution into the capillary channel and polymerizes the acrylamide monomer solution in situ in the capillary channel to form a colloidal filler, thereby achieving the purpose of pouring a solid or extremely viscous gel into the interior of the capillary channel and sealing and storing it, greatly simplifying the complex pre-treatment operations such as capillary electrophoresis channel cleaning, surface coating, and gel filling. In addition, the preparation method and the chip prepared therefrom are based on plastic materials. While the chip material is inexpensive, the various process steps of electrophoresis gel preparation, molding, and sealing are further simplified, significantly reducing the chip cost and making it possible to directly discard the chip after use. In addition, the structural design of the above-mentioned capillary channel no longer depends on the preparation process of the gel. Whether it is a high-concentration viscous LPA gel or a solid acrylamide polymer gel, it can be filled into the interior of the ultra-long capillary channel, achieving complete filling of the solid gel in the capillary channel, making capillary electrophoresis adaptable to a wider range of application scenarios. The above preparation method is designed and constructed for an automated production line, and each process link can be automatically operated in batches on the assembly line, further reducing the production cost of the capillary electrophoresis microfluidic chip and improving production efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0035] Figure 1 A flow chart of a method for preparing a capillary electrophoresis microfluidic chip according to an embodiment of the present invention;

[0036] Figure 2 A schematic structural diagram of a plastic chip body prepared by the method for preparing a capillary electrophoresis microfluidic chip provided in an embodiment of the present invention;

[0037] Figure 3 In one embodiment Figure 2 A local enlarged schematic diagram of point A;

[0038] Figure 4 In another embodiment Figure 2 A local enlarged schematic diagram of point A;

[0039] Figure 5 A cross-sectional view of an aeration device used in the method for preparing a capillary electrophoresis microfluidic chip provided in an embodiment of the present invention;

[0040] Figure 6A top view of an aeration device used in the method for preparing a capillary electrophoresis microfluidic chip provided in an embodiment of the present invention;

[0041] Figure 7 A cross-sectional view of a sealing structure before glue injection used in the method for preparing a capillary electrophoresis microfluidic chip provided in an embodiment of the present invention;

[0042] Figure 8 A bottom view of a sealing structure before glue injection used in the method for preparing a capillary electrophoresis microfluidic chip provided in an embodiment of the present invention;

[0043] Figure 9 A cross-sectional view of a sealing structure after glue injection used in the method for preparing a capillary electrophoresis microfluidic chip provided by an embodiment of the present invention;

[0044] Figure 10 A cross-sectional view of a sealing structure after glue injection used in the method for preparing a capillary electrophoresis microfluidic chip provided in an embodiment of the present invention;

[0045] Figure 11 A schematic diagram of the bonding process of the sealing structure in the method for preparing a capillary electrophoresis microfluidic chip provided by an embodiment of the present invention;

[0046] Figure 12 A partial schematic diagram of a sealing structure of a capillary electrophoresis microfluidic chip produced by the method for preparing a capillary electrophoresis microfluidic chip provided in an embodiment of the present invention.

[0047] in:

[0048] 1 is the plastic chip body; 2 is the capillary channel; 201 is the injection channel arm; 3 is the capillary opening; 4 is the aeration device; 401 is the aeration container; 402 is the air inlet; 403 is the air outlet; 404 is the cavity; 405 is the sealing cover; 5 is the sealing structural part; 501 is the structural part body; 502 is the cavity; 503 is the glue injection groove; 504 is the glue injection hole; 505 is the exhaust hole; 6 is the sealant; 7 is the acrylamide polymer gel; 8 is the pressing head; 9 is the dispensing head. DETAILED DESCRIPTION

[0049] One of the core points of the present invention is to provide a method for preparing a capillary electrophoresis microfluidic chip. This method can inject solid or extremely viscous gel into the interior of the capillary and store it in a sealed manner. At the same time, it simplifies the pre-treatment operations and experimental operation steps of electrophoresis detection, improves the robustness of the system, and reduces costs.

[0050] Another core of the present invention is to provide a capillary electrophoresis microfluidic chip based on the above-mentioned capillary electrophoresis microfluidic chip preparation method.

[0051] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0052] See also Figures 1 to 4 , Figure 1 Flowchart of the method for preparing a capillary electrophoresis microfluidic chip provided by an embodiment of the present invention, Figure 2 A schematic structural diagram of a plastic chip body prepared by the method for preparing a capillary electrophoresis microfluidic chip according to an embodiment of the present invention. Figure 3 In one embodiment Figure 2 A local enlarged schematic diagram of point A, Figure 4 In another embodiment Figure 2 A local enlarged schematic diagram of point A.

[0053] The present invention discloses a method for preparing a capillary electrophoresis microfluidic chip, which comprises the following steps:

[0054] A capillary groove structure is formed on the plastic chip substrate and / or the plastic chip cover, and a capillary opening 3 is formed in one of the plastic chip substrate and the plastic chip cover.

[0055] The present application adopts plastic to prepare the chip, and the plastic material includes but is 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 only one of the plastic chip substrate and the plastic chip cover plate, and the other of the plastic chip substrate and the plastic chip cover plate is not processed with the capillary groove structure and is a smooth structure. Of course, capillary groove structures of corresponding shapes can also 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 cooperate with each other to form a capillary channel 2. The capillary opening 3 can be provided on the one of the plastic chip substrate and the plastic chip cover plate that is not processed with the capillary groove structure, as long as it 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, which is not limited here. In one embodiment of the present application, the cross-sectional area of ​​the capillary channel 2 is preferably 3×10 2 μm 2 ~3×10 4 μm 2The plastic chip substrate and the plastic chip cover are bonded and packaged to form a plastic chip body 1. The capillary groove structure is surrounded by a capillary channel 2. The capillary channel 2 has two to three injection channel arms 201. One end of the injection channel arm 201 is connected to the capillary opening 3, and the other end of each injection channel arm 201 forms a cross or T-shaped cross structure.

[0056] It should be noted that the shape of the plastic chip body 1 is square or rectangular, and the capillary channel 2 thereon must have 2 to 3 injection channel arms 201 in a cross or T-shaped cross structure, such as Figure 3 As shown, when the capillary channel 2 has two sampling channel arms 201, a T-shaped cross structure is formed between the two sampling channel arms 201 and the main channel of the capillary channel 2, as shown in FIG. Figure 4 As shown, when the capillary channel 2 has three sampling channel arms 201, a cross structure is formed between the three sampling channel arms 201 and the main channel of the capillary channel 2, and then the process method described in this application can be used for processing, production and preparation.

[0057] The inner wall of the capillary channel 2 is surface treated.

[0058] Depending on the type of plastic, the surface treatment steps are not exactly the same. Generally speaking, surface treatment includes surface cleaning and chemical modification. Of course, some types of plastics only require surface cleaning and do not require chemical modification.

[0059] An acrylamide monomer solution is injected into the capillary channel 2 , and the plastic chip body 1 is exposed to a low temperature and protective gas aeration environment to cause the acrylamide monomer solution to undergo in-situ polymerization reaction in the capillary channel 2 to form a colloidal filler.

[0060] The colloidal filler formed by the in-situ polymerization reaction is an acrylamide polymer gel such as linear polyacrylamide and methylene acrylamide, and the polymerization can be initiated by various methods such as chemical initiation and photoinitiation.

[0061] The preparation method in the embodiment of the present application is only for acrylamide gel. The acrylamide polymerization reaction is an anaerobic reaction and the presence of air needs to be excluded. Therefore, during the polymerization process, protective gas aeration needs to be used to protect the plastic chip body 1. The protective gas used in the embodiment of the present application is common argon and nitrogen. Of course, in other embodiments, other protective gases that meet the requirements can also be used. This is not limited here, and it needs to be carried out at low temperature to avoid high temperature causing free radicals to be oxidized and lead to polymerization termination.

[0062] The capillary opening 3 is encapsulated by a sealing structure 5 to form a capillary electrophoresis microfluidic chip.

[0063] The sealing structure 5 is preferably made of the same material as the plastic chip body 1 , and is mainly used for sealing and bonding to the capillary opening 3 of the plastic chip body 1 to form a complete seal and achieve long-term storage of the acrylamide gel in the capillary channel 2 .

[0064] It can be seen that compared with the prior art, the capillary electrophoresis microfluidic chip preparation method provided in the embodiment of the present invention is to inject acrylamide monomer solution into the capillary channel 2 and polymerize the acrylamide monomer solution in situ in the capillary channel 2 to form a colloidal filler, thereby achieving the purpose of pouring a solid or extremely viscous gel into the interior of the capillary and sealing it for storage, greatly simplifying the complex pre-treatment operations such as capillary electrophoresis channel cleaning, surface coating, and glue filling. In addition, the preparation method and the chip prepared therefrom are based on plastic materials. While the chip material is inexpensive, the various process steps of electrophoresis gel preparation, molding, and sealing are further simplified, significantly reducing the chip cost and making it possible to directly discard the chip after use. In addition, the structural design of the capillary channel 2 no longer depends on the preparation process of the gel. Whether it is a high-concentration viscous LPA gel or a solid acrylamide polymer gel, it can be filled into the interior of the ultra-long capillary channel 2, achieving complete filling of the solid gel in the capillary channel 2, so that capillary electrophoresis can be adapted to a richer range of application scenarios. The above preparation method is designed and constructed for an automated production line, and each process link can be automatically operated in batches on the assembly line, further reducing the production cost of the capillary electrophoresis microfluidic chip and improving production efficiency.

[0065] 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 a stamping or injection molding process. The plastic chip substrate and the plastic chip cover plate are packaged by a thermocompression bonding process and / or a laser bonding process. Of course, it is not difficult to understand that the above-mentioned capillary groove structure and capillary opening 3 molding method and the packaging method of the plastic chip body 1 are merely preferred embodiments provided in the embodiments of the present application and are not actually limited to the above-mentioned contents. Those skilled in the art can select appropriate methods to achieve molding and packaging as needed.

[0066] Specifically, in the above-mentioned preparation method, the surface treatment of the inner wall of the capillary channel 2 includes:

[0067] The surface treatment process is determined according to the material of the plastic chip body 1. The surface treatment process is to clean the inner wall of the capillary channel 2 with a cleaning solvent, or to clean the inner wall of the capillary channel 2 with a cleaning solvent and then coat the inner wall of the capillary channel 2 with a chemical modification solvent.

[0068] For different types of plastics, the surface treatment process varies greatly. Taking COP plastic as an example, this type of plastic does not require chemical modification, only the surface of the capillary channel 2 needs to be cleaned. The capillary channel 2 can be repeatedly cleaned with solvents such as ethanol and water. After drying, an electrically neutral surface can be obtained. PC plastic, on the other hand, requires chemical modification. The capillary channel 2 needs to be repeatedly cleaned with solvents such as ethanol and water, and after drying, the inner wall of the capillary channel 2 is coated with DEH solvent.

[0069] The inner wall of the capillary channel 2 is surface treated by using a certain surface treatment process.

[0070] After the surface treatment process is determined, the inner wall of the capillary channel 2 is surface treated according to the surface treatment process.

[0071] In order to ensure the smooth progress of in-situ polymerization, the embodiment of the present application provides a device specifically for protective gas aeration, and the in-situ polymerization process is carried out in the aeration device 4. Figure 5 and Figure 6 As shown, the aeration device 4 includes an aeration container 401 and a sealing cover 405, wherein the aeration container 401 has an air inlet 402 and an air outlet 403 for accessing the protective gas circuit system, the air inlet 402 and the air outlet 403 are connected to the cavity 404 of the aeration container 401, and the cavity 404 has a chip inlet and outlet. The sealing cover 405 is sealed with the aeration container 401 to seal the chip inlet and outlet.

[0072] In a specific embodiment of the present application, the cavity 404 of the aeration container 401 is boat-shaped, and the bottom of the cavity 404 is a relatively wide plane. Multiple plastic chip bodies 1 filled with acrylamide monomer solution are placed horizontally and side by side with their capillary openings 3 facing upward on the bottom plane of the container. Protective gas is introduced from the air inlet 402. Under the action of the internal structure of the aeration container 401, the protective gas is discharged to the air outlet 403 on the other side at a constant flow and pressure to exhaust the air and ensure that the plastic chip body 1 is completely covered by the protective gas. At the same time, since the polymerization process needs to be carried out at low temperature, the aeration container 401 is made of a good thermal conductor material, such as stainless steel or aluminum alloy. For easy observation, the sealing cover 405 is made of a transparent material, such as glass or acrylic material. A sealing ring is set between the sealing cover 405 and the aeration container 401 for sealing.

[0073] Based on the above-mentioned aeration device 4, in a specific embodiment of the present application, the in-situ polymerization process includes:

[0074] A plurality of plastic chip bodies 1 filled with acrylamide monomer solution are placed in an aeration container 401, and the capillary openings 3 of each plastic chip body 1 are placed horizontally and side by side with the capillary openings 3 facing upward. After the plastic chip bodies 1 are arranged in the aeration container 401, the sealing cover 405 is placed on the aeration container 401 to form a sealed aeration space.

[0075] The aeration device 4 is connected to the protective gas gas path system through the air inlet 402 and the air outlet 403 at both ends, and the protective gas is introduced into the cavity 404 of the aeration container 401, and the aeration device 4 is placed in a cold output device. It should be noted that the cold output device can be a refrigerator, an ice box, etc., and the temperature of the protective gas can also be controlled to achieve temperature control of the environment in which the plastic chip body 1 is located, and the protective gas flow and pressure are adjusted to be stable to start the in-situ polymerization reaction.

[0076] like Figure 7 and Figure 8 As shown, in one embodiment of the present application, the sealing structure 5 includes a structural member body 501, and the surface of the structural member body 501 that contacts the plastic chip body 1 is provided with a cavity 502 and a glue injection groove 503 provided around the cavity 502. The cavity 502 is used to cover the capillary opening 3, and the glue injection groove 503 is connected with a glue injection hole 504 and an exhaust hole 505. The glue injection hole 504 and the exhaust hole 505 extend to the surface of the structural member body 501 that is back to the plastic chip body 1.

[0077] When bonding the sealing structure 5 to the plastic chip body 1, as shown in FIG. Figure 9 and Figure 10 As shown, sealant 6 is injected into the injection hole 504, and the sealant 6 enters the injection groove 503 from the injection hole 504 and gradually fills the injection groove 503. At the same time, the gas in the sealing structure 5 is discharged from the exhaust hole 505. When the sealant 6 can be observed in the exhaust hole 505, it means that the sealant 6 is filled.

[0078] Based on the above-mentioned sealing structure 5, in a specific embodiment of the present application, the sealing structure 5 is used to encapsulate the capillary opening 3, including:

[0079] The cavity 502 of the sealing structure 5 is aligned with the capillary opening 3 and is tightly pressed onto the plastic chip body 1 .

[0080] This step needs to be implemented with the help of a pressing mechanism that is compatible with the sealing structure 5. The pressing mechanism has a pressing head 8, which can be made of polytetrafluoroethylene and is provided with a glue injection port and an exhaust port corresponding to the glue injection hole 504 and the exhaust hole 505 on the sealing structure 5 respectively.

[0081] Glue is injected into the glue injection hole 504 of the sealing structural component 5 .

[0082] like Figure 11 As shown, the pressing head 8 presses the sealing structure 5 downward from the top to the part to be bonded of the plastic chip body 1, so that the pressing head 8 and the plastic chip body 1 are relatively fixed, and the dispensing head 9 of the sealant 6 passes through the injection port of the pressing head 8 and presses against the injection hole 504 of the sealing structure 5 to perform the dispensing and injection operations of the sealant 6. After the injection operation of the sealant 6 is completed, the dispensing head 9 is lifted, and then the pressing head 8 is lifted to complete the entire packaging process of the capillary electrophoresis microfluidic chip. Figure 12 shown.

[0083] It should be noted that in order to ensure the bonding effect between the sealing structure 5 and the plastic chip body 1, in one embodiment of the present application, before using the sealing structure 5 to encapsulate the capillary opening 3, the excess acrylamide polymer gel 7 at the capillary opening 3 is removed to avoid the acrylamide polymer gel 7 overflowing from the capillary channel 2 during the in-situ polymerization process affecting the bonding effect between the sealing structure 5 and the plastic chip body 1.

[0084] The embodiment of the present application also provides a capillary electrophoresis microfluidic chip made based on the capillary electrophoresis microfluidic chip preparation method described in the above embodiment, the capillary electrophoresis microfluidic chip includes a plastic chip body 1 and a sealing structure 5, wherein the material of the plastic chip body 1 includes but is not limited to COP plastic and PC plastic, the plastic chip body 1 contains a capillary channel 2, and the capillary channel 2 stores an acrylamide polymer gel 7, the capillary channel 2 has 2 to 3 sampling channel arms 201, one end of the sampling channel arm 201 is connected to a capillary opening 3, and the other end of each sampling channel arm 201 forms a cross or T-shaped cross structure, the sealing structure 5 is sealed and bonded to the plastic chip body 1 to cover the capillary opening 3, and the capillary electrophoresis microfluidic chip is made of plastic, which is low in price and further simplifies the various process steps of electrophoresis gel preparation, molding, and sealing, thereby significantly reducing the chip cost and making it possible to directly discard the chip after use. At the same time, the acrylamide polymer gel 7 is directly stored in the capillary channel 2, which greatly simplifies the complex pre-treatment operations such as capillary electrophoresis channel cleaning, surface coating, and gel filling.

[0085] To further optimize the above technical solution, in a specific embodiment, the plastic chip body 1 includes a plastic chip base and a plastic chip cover plate, a capillary groove structure is provided in the plastic chip base and / or the plastic chip cover plate, a capillary opening 3 is provided in the plastic chip base and the plastic chip cover plate, the plastic chip base and the plastic chip cover plate are bonded and adhered to each other to enclose the capillary groove structure into a capillary channel 2, and are bonded and packaged into the plastic chip body 1.

[0086] like Figure 7 、 Figure 8 and Figure 12As shown, in one embodiment of the present application, the sealing structure 5 includes a structural member body 501, and the surface of the structural member body 501 that contacts the plastic chip body 1 is provided with a cavity 502 and a glue injection groove 503 provided around the cavity 502. The cavity 502 is used to cover the capillary opening 3, and the glue injection groove 503 is connected with a glue injection hole 504 and an exhaust hole 505. The glue injection hole 504 and the exhaust hole 505 extend to the surface of the structural member body 501 that is back to the plastic chip body 1.

[0087] In the present application, the acrylamide polymer gel 7 is formed by cross-linking and polymerization of one or more combinations of acrylamide, methylene acrylamide, and methylene bisacrylamide. The acrylamide polymer gel 7 is a non-Newtonian fluid or solid. Of course, it should be noted that acrylamide, methylene acrylamide, and methylene bisacrylamide are only preferred solutions provided in the embodiments of the present application. In fact, they are not limited to these three types, and other acrylamide substances can also be used.

[0088] The various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referenced to each other.

[0089] The above description of the disclosed embodiments is intended to enable one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not limited to the embodiments shown herein but is intended to conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing a capillary electrophoresis microfluidic chip, characterized in that: Including steps: forming a capillary groove structure on a plastic chip substrate and / or a plastic chip cover, and forming a capillary opening in one of the plastic chip substrate and the plastic chip cover; The plastic chip base and the plastic chip cover are bonded and packaged into a plastic chip body, and the capillary groove structure is surrounded by a capillary channel, wherein the capillary channel has 2 to 3 sampling channel arms, one end of each sampling channel arm is connected to the capillary opening, and the other end of each sampling channel arm forms a cross or T-shaped cross structure; performing surface treatment on the inner wall of the capillary channel; injecting an acrylamide monomer solution into the capillary channel, and exposing the plastic chip body to a low temperature and protective gas aeration environment to cause the acrylamide monomer solution to undergo an in-situ polymerization reaction in the capillary channel to form a colloidal filler; The capillary opening is packaged with a sealing structure to form a capillary electrophoresis microfluidic chip.

2. The method for preparing a capillary electrophoresis microfluidic chip according to claim 1, wherein: The plastic chip substrate and the plastic chip cover 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: The in-situ polymerization process is carried out in an aeration device, which includes: An aeration container, the aeration container having an air inlet and an air outlet for accessing a protective gas circuit system, the air inlet and the air outlet being in communication with a cavity of the aeration container, the cavity having a chip inlet and outlet; A sealing cover plate is sealed and matched with the aeration container to cover the chip inlet and outlet.

4. The method for preparing a capillary electrophoresis microfluidic chip according to claim 3, wherein: The in-situ polymerization process comprises: Placing a plurality of plastic chip bodies filled with acrylamide monomer solution with the capillary openings facing upwards, horizontally and side by side in the aeration container, and sealing the aeration container with the sealing cover plate; The aeration device is connected to the protective gas gas circuit system, and the aeration device is placed in the cold output device, and the protective gas flow and pressure are adjusted to be stable, and the in-situ polymerization reaction is started.

5. The method for preparing a capillary electrophoresis microfluidic chip according to claim 1, wherein: The sealing structural component includes a structural component body, a surface of the structural component body that is in contact with the plastic chip body is provided with a cavity and a glue injection groove provided around the cavity, the cavity is used to cover the capillary opening, the glue injection groove is connected with a glue injection hole and an exhaust hole, and the glue injection hole and the exhaust hole extend to the surface of the structural component body that is away from the plastic chip body.

6. The method for preparing a capillary electrophoresis microfluidic chip according to claim 5, wherein: The encapsulating the capillary opening by using a sealing structure comprises: Aligning the cavity of the sealing structure with the capillary opening and pressing it tightly against the plastic chip body; Glue is injected into the glue injection hole of the sealing structural component.

7. A capillary electrophoresis microfluidic chip manufactured based on the method for preparing a capillary electrophoresis microfluidic chip according to any one of claims 1 to 6, characterized in that: include: A plastic chip body having a capillary channel within the plastic chip body, wherein the capillary channel stores an acrylamide polymer gel, the capillary channel having 2 to 3 injection channel arms, one end of each injection channel arm being connected to a capillary opening, and the other end of each injection channel arm forming a cross or T-shaped cross structure; A sealing structure is sealed and bonded to the plastic chip body to cover the capillary opening.

8. The capillary electrophoresis microfluidic chip according to claim 7, characterized in that: The plastic chip body includes a plastic chip base and a plastic chip cover plate. A capillary groove structure is provided on the plastic chip base and / or the plastic chip cover plate. The capillary opening is provided on one of the plastic chip base and the plastic chip cover plate. The plastic chip base and the plastic chip cover plate are bonded and adhered to each other to enclose the capillary groove structure into the capillary channel, and are bonded and packaged into the plastic chip body.

9. The capillary electrophoresis microfluidic chip according to claim 7, characterized in that: The sealing structural component includes a structural component body, a surface of the structural component body that is in contact with the plastic chip body is provided with a cavity and a glue injection groove provided around the cavity, the cavity is used to cover the capillary opening, the glue injection groove is connected with a glue injection hole and an exhaust hole, and the glue injection hole and the exhaust hole extend to the surface of the structural component body that is away from the plastic chip body.

10. The capillary electrophoresis microfluidic chip according to claim 7, characterized in that: The acrylamide polymer gel is formed by cross-linking and polymerization of one or more combinations of acrylamide, methylene acrylamide, and methylene bisacrylamide. The acrylamide polymer gel is a non-Newtonian fluid or a solid.

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