Microfluidic chip and preparation method thereof
The microfluidic chip, with its layered structure and vertical electrode design, solves the problem of achieving three-dimensional structures in existing technologies, improves production efficiency and reduces costs, and is suitable for a variety of detection needs.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- 广州市科易成新材料有限公司
- Filing Date
- 2024-07-10
- Publication Date
- 2026-07-31
AI Technical Summary
Existing microfluidic chip fabrication methods are difficult to use to create three-dimensional structures, resulting in difficulties in meeting the requirements of testing projects, low production efficiency, and high costs.
The microfluidic chip design employs a layered structure, with functional structures mounted on different layers that provide light transmission, light shielding, electrical conductivity, thermal conductivity, and filtration. Each layer is fabricated using processes such as photolithography and die-cutting, and multiple detections are achieved through vertical electrodes.
This technology enables high applicability and low-cost production of microfluidic chips, lowers the technical threshold, improves detection efficiency and accuracy, and is suitable for mass production.
Smart Images
Figure CN118874565B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of microfluidic chip technology, and in particular to a microfluidic chip and its fabrication method. Background Technology
[0002] Microfluidic chips are a technology that integrates basic operational units such as sample preparation, reaction, separation, and detection in biological, chemical, and medical analysis processes onto a single chip at the micrometer scale, automating the entire analytical system. Due to its enormous potential in biology, chemistry, and medicine, it has developed into a new interdisciplinary research field combining biology, chemistry, medicine, fluid mechanics, electronics, materials science, and mechanical engineering. This microfluidic chip technology is characterized by high efficiency, low cost, and ease of adoption. Microfluidic chips integrate functional modules such as microchannels, micropumps, microvalves, microreservoirs, microelectrodes, microdetectors, windows, and connectors onto chip materials using microfabrication techniques, much like integrated circuits. Chip fabrication materials have evolved from silicon wafers to glass, quartz, and organic polymers. Therefore, the processing technology for organic polymer materials is also continuously developing. New methods such as fuzzy lithography, thermoforming, laser ablation, and soft lithography have been developed based on traditional photolithography and etching.
[0003] Research on microfluidic chip-based micro total analysis systems is an important direction and frontier in the development of analytical instruments. Currently, microfluidic chips are mainly fabricated using methods such as photolithography or thermoforming. Due to limitations in these methods, it is difficult to create three-dimensional structures using photolithography and thermoforming. Therefore, the microfluidic chips currently used are mainly two-dimensional, which makes it difficult to meet the needs of different detection projects. Summary of the Invention
[0004] One of the objectives of this invention is to overcome the shortcomings of the prior art and provide a microfluidic chip that aims to improve the production efficiency and reduce the production cost of the microfluidic chip. It can carry the various functional structures of the microfluidic chip on different functional layers through a layered structure. At the same time, each functional layer has the functions of light transmission, light shielding, electrical conductivity, thermal conductivity and filtration. It has high applicability and features simple processing, low processing cost and precise control of microchannel structure.
[0005] The second objective of this invention is to provide a method for fabricating a microfluidic chip.
[0006] One of the objectives of this invention is achieved through the following technical solution:
[0007] A microfluidic chip is provided, comprising a first functional layer, a second functional layer and a third functional layer stacked together.
[0008] The first functional layer is provided with an inlet and an outlet;
[0009] The second functional layer includes a thin film layer, on which at least one microchannel is provided, penetrating the thickness direction of the thin film layer, and the microchannel corresponds to the inlet and the outlet respectively;
[0010] The third functional layer is provided with a microelectrode layer corresponding to the microchannel;
[0011] The first functional layer, the second functional layer, and the third functional layer are each composed of at least one of a light-transmitting layer, a light-shielding layer, a conductive layer, a heat-conducting layer, and a filter layer.
[0012] In one possible implementation of the first aspect above, the microelectrode layer includes an electrode layer formed on the third functional layer, the electrode layer extending vertically from the top of the third functional layer toward the bottom of the first functional layer, the top of the third functional layer being one end face of the third functional layer toward the second functional layer, and the bottom of the first functional layer being one end face of the first functional layer toward the second functional layer.
[0013] In one possible implementation of the first aspect described above, the first functional layer, the second functional layer, and the third functional layer are each made of any one of the following materials: plastic, glass, monocrystalline silicon, and metal.
[0014] In one possible implementation of the first aspect above, the light-transmitting layer is made of any one of polyethylene terephthalate, polyimide, cyclic olefin copolymer, polycarbonate, acrylonitrile-butadiene-styrene, ethylene vinyl acetate and polyvinyl chloride.
[0015] The light-shielding layer is made of a composite black masterbatch of any one of the following materials: polyethylene terephthalate, polyimide, cyclic olefin copolymer, polycarbonate, acrylonitrile-butadiene-styrene, ethylene vinyl acetate, and polyvinyl chloride, or it is made of glass by printing with black screen printing ink.
[0016] In one possible implementation of the first aspect above, the conductive layer is made of any one of the following film materials: Si single crystal thin film, doped polycrystalline silicon thin film, semi-insulating polycrystalline silicon thin film, copper foil, aluminum foil, gold foil, and nickel-chromium alloy foil.
[0017] The thermally conductive layer is made of any one of the following materials: polyethylene terephthalate, polyimide, cyclic olefin copolymer, polycarbonate, acrylonitrile-butadiene-styrene, ethylene vinyl acetate, and polyvinyl chloride; wherein the thermally conductive filler includes at least one of aluminum nitride, boron nitride, silicon carbide, carbon nanotubes, and graphene.
[0018] The filter layer includes a microporous filter membrane.
[0019] The microfluidic chip of the present invention has the following beneficial effects:
[0020] (1) The microfluidic chip provided by the present invention adopts a layered structure, dividing the microfluidic chip into three functional layers. The first functional layer has an inlet and outlet for chip sample detection, the second functional layer has a flow channel for sample detection, and the third functional layer has a detection means for realizing sample detection. Additional light transmission, light blocking, electrical conductivity, thermal conductivity and filtering functions can be added between each functional layer according to actual needs, which has a wide range of detection applicability. Each functional layer can be selected by one or more arbitrary combinations, which reduces the requirements of the microfluidic chip for external devices and external environment, making it more suitable for a more relaxed application environment.
[0021] (2) The functional structure between each functional layer can be completed by individual processing. The film thickness in the second functional layer can be adjusted according to actual needs, so that microchannels of different sizes can be realized, and the detection flow rate of samples can be controlled arbitrarily, thereby optimizing the detection performance and detection efficiency of microfluidic chips. Under this setting, there is no need to use a photolithography machine, which can significantly reduce the technical threshold and production cost of microfluidic chips.
[0022] (3) The layered construction method realizes the coordination between the various functional structural units of the microfluidic chip, which reduces the probability of deformation during assembly and can improve the quality level of the microfluidic chip.
[0023] The second objective of this invention is achieved through the following technical solution:
[0024] The method for fabricating the aforementioned microfluidic chip includes the following steps:
[0025] It provides a first functional layer, a second functional layer, and a third functional layer;
[0026] An inlet and an outlet are fabricated on the first functional layer;
[0027] Microchannels are fabricated on the second functional layer, with the two ends of the microchannels corresponding to the inlet and outlet.
[0028] A microelectrode layer is fabricated on the third functional layer, and the microelectrode layer has multiple probe ends that are in contact with the microchannel;
[0029] The first functional layer, the second functional layer, and the third functional layer are stacked sequentially, aligned, and then pressed and sealed to obtain a microfluidic chip.
[0030] In one possible implementation of the second aspect above, processing the inlet and outlet on the first functional layer specifically includes: etching patterns on the first functional layer by photolithography and die-cutting processes to form the inlet and outlet along the thickness direction of the first functional layer.
[0031] In one possible implementation of the second aspect above, fabricating microchannels on the second functional layer specifically includes: providing a membrane, and etching patterns on the membrane using photolithography, die-cutting, and nanoimprint lithography processes to form the microchannels.
[0032] In one possible implementation of the second aspect above, the fabrication of the microelectrode layer on the third functional layer specifically includes: etching a pattern corresponding to the microchannel on the third functional layer by photolithography and die-cutting processes, and forming the microelectrode layer on the corresponding pattern by metal injection or filling with conductive paste.
[0033] The microfluidic chip fabrication method provided in this application can have the following beneficial effects:
[0034] (1) The present invention uses a light-transmitting layer, a light-shielding layer, a conductive layer, a heat-conducting layer and a filter layer as three functional layers in its structure, which can realize a variety of different functional combinations to meet different detection needs.
[0035] (2) The thickness of the thin film layer in the second functional layer of the present invention can be adjusted arbitrarily, so that the prepared microchannel can form a three-dimensional flow channel structure, thereby achieving the purpose of accelerating fluid mixing and increasing throughput.
[0036] (3) By constructing the various functional structures of the microfluidic chip in layers, rapid production can be achieved through the cooperation of multiple production lines. Compared with existing technologies, production costs can be significantly reduced, making it suitable for mass production. Attached Figure Description
[0037] The above and other objects, features and advantages of this application will become more apparent from the more detailed description of exemplary embodiments thereof in conjunction with the accompanying drawings, wherein the same reference numerals generally represent the same components in the exemplary embodiments thereof.
[0038] Figure 1 This is a schematic diagram of the structure of a microfluidic chip shown in an embodiment of this application;
[0039] Figure 2 This is another schematic diagram of the microfluidic chip shown in the embodiments of this application;
[0040] Figure 3 This is another schematic diagram of the microfluidic chip shown in the embodiments of this application;
[0041] Figure 4 This is a flowchart illustrating a microfluidic chip fabrication method according to an embodiment of this application.
[0042] Figure label:
[0043] 1. First functional layer; 11. Inlet; 12. Outlet; 2. Second functional layer; 21. Microchannel; 3. Third functional layer; 31. Microelectrode layer. Detailed Implementation
[0044] Preferred embodiments of the present application will now be described in more detail with reference to the accompanying drawings. While preferred embodiments of the present application are shown in the drawings, it should be understood that the present application may be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided to make the present application more thorough and complete, and to fully convey the scope of the present application to those skilled in the art.
[0045] In the description of this invention, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.
[0046] In the description of this invention, the term "and / or" is merely a description of the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, or B existing alone. Additionally, the character " / " in this document generally indicates that the preceding and following related objects have an "or" relationship.
[0047] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.
[0048] Microfluidic chips are a technology that integrates basic operational units such as sample preparation, reaction, separation, and detection in biological, chemical, and medical analysis processes onto a single chip at the micrometer scale, automating the entire analytical system. Due to its enormous potential in biology, chemistry, and medicine, it has developed into a new interdisciplinary research field combining biology, chemistry, medicine, fluid mechanics, electronics, materials science, and mechanical engineering. This microfluidic chip technology is characterized by high efficiency, low cost, and ease of adoption. Microfluidic chips integrate functional modules such as microchannels, micropumps, microvalves, microreservoirs, microelectrodes, microdetectors, windows, and connectors onto chip materials using microfabrication techniques, much like integrated circuits. Chip fabrication materials have evolved from silicon wafers to glass, quartz, and organic polymers. Therefore, the processing technology for organic polymer materials is also continuously developing. New methods such as fuzzy lithography, thermoforming, laser ablation, and soft lithography have been developed based on traditional photolithography and etching.
[0049] Research on microfluidic chip-based micro total analysis systems is an important direction and frontier in the development of analytical instruments. Currently, microfluidic chips are mainly fabricated using methods such as photolithography or thermoforming. Due to limitations in these methods, it is difficult to create three-dimensional structures using photolithography and thermoforming. Therefore, the microfluidic chips currently used are mainly two-dimensional, which makes it difficult to meet the needs of different detection projects.
[0050] To address the aforementioned issues, this application provides a microfluidic chip and its fabrication method, aiming to improve the production efficiency and reduce the production cost of the microfluidic chip. It can carry the various functional structures of the microfluidic chip on different functional layers through a layered construction method. At the same time, each functional layer has the functions of light transmission, light shielding, electrical conductivity, thermal conductivity and filtration. It has high applicability and features simple processing, low processing cost and precise controllable microchannel structure.
[0051] In a typical embodiment of the present invention, a microfluidic chip is provided, wherein the three functional layers with different basic structures can be selected as one or more of the following as the base layer: a light-transmitting layer, a light-shielding layer, a conductive layer, a thermally conductive layer, and a filter layer, which can greatly improve the application effect and application range of the microfluidic chip.
[0052] In one embodiment of the present invention, please refer to Figure 1 and Figure 2 A microfluidic chip is provided, comprising a first functional layer 1, a second functional layer 2 and a third functional layer 3 stacked together.
[0053] The first functional layer 1 is provided with an inlet 11 and an outlet 12;
[0054] The second functional layer 2 includes a thin film layer, on which at least one microchannel 21 is provided, penetrating the thickness direction of the thin film layer, and the microchannel 21 corresponds to the inlet 11 and the outlet 12 respectively.
[0055] The third functional layer 3 is provided with a microelectrode layer 31 corresponding to the microchannel 21;
[0056] The first functional layer 1, the second functional layer 2, and the third functional layer 3 are each composed of at least one of a light-transmitting layer, a light-shielding layer, a conductive layer, a heat-conducting layer, and a filter layer.
[0057] In this invention, the first functional layer 1 may be selected from one or more of the following: a light-transmitting layer, a light-shielding layer, a conductive layer, a heat-conducting layer, and a filter layer.
[0058] In this invention, the second functional layer 2 can be selected from one or more of the following: a light-transmitting layer, a light-shielding layer, a conductive layer, a heat-conducting layer, and a filter layer.
[0059] In this invention, the third functional layer 3 can be selected from one or more of the following: a light-transmitting layer, a light-shielding layer, a conductive layer, a heat-conducting layer, and a filter layer.
[0060] For example, the first functional layer 1 can be a light-transmitting layer, the second functional layer 2 can be a double-layered conductive layer, with the conductive layers respectively stacked on the thin film layer, and the third functional layer can be a light-shielding layer.
[0061] The term "corresponding" means that when the various functional layers of the microfluidic chip are stacked and aligned, the projections of identical components (such as the sample outlet 12 and sample inlet 11, microchannel 21, microelectrode layer 31, etc.) coincide in the vertical direction.
[0062] In practical applications, the microelectrode layer 31 on the third functional layer 3 can be configured as a planar electrode or a vertical electrode (i.e., an embedded electrode). When a planar electrode is used, the projection of the microchannel 21 and the planar electrode coincides in the vertical direction. This means that when liquid flows through the microchannel 21, the planar electrode can contact the liquid, thereby achieving the corresponding detection function. When a vertical electrode is used, please refer to [the relevant documentation]. Figure 3 The embedded electrode has its starting end on the third functional layer 3 and its ending end on the first functional layer 1. With this configuration, the film thickness and number of layers in the second functional layer 2 can be arbitrarily selected, and different microchannel 21 structures can be set on each film layer, thus achieving multiple detection effects on a single microfluidic chip. Correspondingly, the sample inlet 11 and sample outlet 12 set on the first functional layer 1 correspond to the number of microchannels 21 on the second functional layer 2, and it is only necessary that the vertical electrode can simultaneously contact each microchannel 21.
[0063] Based on the detection accuracy requirements and sample liquid throughput needs of the microfluidic chip, selecting appropriate microchannel 21 dimensions and tolerance ranges can ensure the functional requirements of the microfluidic chip while also considering manufacturing costs and processes, thus improving the economics of mass production. In a preferred embodiment, the width of the microchannel 21 constructed in the thin film layer is greater than 1 mm.
[0064] It should be noted that the first functional layer 1, the second functional layer 2, and the third functional layer 3 in this invention can be arbitrarily selected from the above-mentioned specific functional layers. The above examples are only one of the selected implementation schemes to facilitate those skilled in the art to understand the technical solution of this invention.
[0065] In a preferred embodiment of the present invention, the microelectrode layer 31 of the microfluidic chip includes an electrode layer formed on the third functional layer 3. The electrode layer extends vertically from the top of the third functional layer 3 toward the bottom of the first functional layer 1. The top of the third functional layer 3 is one end face of the third functional layer 3 facing the second functional layer 2, and the bottom of the first functional layer 1 is one end face of the first functional layer 1 facing the second functional layer 2.
[0066] As mentioned above, when the number of thin film layers in the second functional layer 2 is one, the microelectrode layer 31 can be set as a planar electrode or a vertical electrode. When the number of thin film layers in the second functional layer 2 is two or more, setting a vertical electrode in the microfluidic chip can save a lot of electrode circuit design and avoid the microfluidic chip structure from being too bulky.
[0067] In practical production applications, the microelectrode layer 31 can also directly penetrate the first functional layer 1, the second functional layer 2, and the third functional layer 3 (i.e., the thickness direction of the microfluidic chip). This setting can improve the production yield, and during alignment and bonding, it can be fixed through the microelectrode hole, thereby improving the yield of the microfluidic chip.
[0068] In a preferred embodiment of the present invention, the first functional layer 1, the second functional layer 2 and the third functional layer 3 of the microfluidic chip are respectively made of any one of the following materials: plastic, rubber, glass, monocrystalline silicon and metal.
[0069] In practical applications, structural models of each functional layer of a microfluidic chip can be built using software. The bonding of the first functional layer 1, the second functional layer 2, and the third functional layer 3 can be achieved using adhesive bonding. Specifically, double-sided adhesive material is bonded to each functional layer. Laser processing can be used to process each structure; the laser, based on the flow channel pattern, processes and penetrates the corresponding functional layer along a trajectory, obtaining the structure of each functional layer, forming a structure such as... Figure 1The diagram shows the structure. Then, the double-sided adhesive film attached to each functional layer is peeled off, and each functional layer is positioned and aligned using an external device. They are then bonded together in sequence to obtain the microfluidic chip.
[0070] When detecting different samples or different throughputs, the overall material of the microfluidic chip varies slightly. Therefore, the first functional layer 1, the second functional layer 2, and the third functional layer 3 can all be made of plastic, rubber, glass, monocrystalline silicon, or metal to improve the adaptability of the microfluidic chip.
[0071] The electrode layer extends vertically from the top of the third functional layer 3 toward the bottom of the first functional layer 1, forming a buried electrode. The orientation of the buried electrode can be implemented in the following ways.
[0072] In one feasible approach, the third functional layer 3 is a corresponding plate made of glass or monocrystalline silicon, which is obtained by drilling, milling or laser cutting, cleaning, metallizing and electroplating.
[0073] In another feasible approach, the third functional layer 3 is a corresponding plate made of plastic material, which can be prepared by injection molding and the corresponding holes are formed directly in the plastic material by injection molding, and then the corresponding vertical electrodes are obtained by metal injection molding.
[0074] In another feasible approach, the third functional layer 3 is a thin film made of plastic material. Corresponding holes are etched on the film using laser micro-hole cutting, conductive paste is rolled into the holes to embed the conductive paste into the holes, and then cured and shaped.
[0075] Compared with the prior art, one of the innovations of this application is the design of a vertical electrode. Through the designed vertical electrode, multiple non-connected microchannels 21 can be arranged on a microfluidic chip, thereby enabling multiple detections on a single microfluidic chip.
[0076] In a preferred embodiment of the present invention, the light-transmitting layer of the microfluidic chip is made of any one of polyethylene terephthalate, polyimide, cyclic olefin copolymer, polycarbonate, acrylonitrile-butadiene-styrene, ethylene vinyl acetate and polyvinyl chloride.
[0077] The light-shielding layer is made of a composite black masterbatch of any one of the following materials: polyethylene terephthalate, polyimide, cyclic olefin copolymer, polycarbonate, acrylonitrile-butadiene-styrene, ethylene vinyl acetate, and polyvinyl chloride, or it is made of glass by printing with black screen printing ink.
[0078] In a preferred embodiment, the light-shielding layer can be formed by mixing polyethylene terephthalate (PET) and a special polyester masterbatch in a certain proportion, followed by drying, melting, extrusion, casting, and longitudinal and transverse stretching. The film prepared from polyethylene terephthalate (PET) composite black masterbatch has the following advantages: good black coverage, uniform color, smooth and flat surface, colorfastness, odorless, tasteless, non-toxic, good flexibility, no water ripples on the surface, no crystal points, excellent impact resistance, corrosion resistance, excellent insulation, excellent mechanical properties, high rigidity, hardness, and toughness, puncture resistance, abrasion resistance, small thickness tolerance, low thermal shrinkage, strong durability, low shrinkage, low water absorption, smooth and glossy surface, excellent creep resistance, fatigue resistance, abrasion resistance, dimensional stability, high temperature and low temperature resistance, high chemical resistance, oil resistance, and airtightness.
[0079] When the sample liquid flows through the fully transparent microchannel 21 during use, it will be affected by the ambient light, resulting in errors during measurement or counting. Therefore, by setting a light-shielding layer in any one or all of the first functional layer 1, the second functional layer 2, and the third functional layer 3, excess light from the light source can be blocked, thereby ensuring the accuracy of the sample liquid during measurement.
[0080] In the prior art, the astigmatism angle of the microchannel 21 is generally 180° when conventionally observed. However, with the light-shielding layer of the present invention, vertical observation at 90° (i.e., the thickness direction of the microfluidic chip) can be achieved, which effectively improves the detection accuracy.
[0081] In a preferred embodiment of the present invention, the conductive layer of the microfluidic chip is made of any one of the following film materials: Si single crystal thin film, doped polycrystalline silicon thin film, semi-insulating polycrystalline silicon thin film, copper foil, aluminum foil, gold foil, and nickel-chromium alloy foil.
[0082] The thermally conductive layer is made of any one of the following materials: polyethylene terephthalate, polyimide, cyclic olefin copolymer, polycarbonate, acrylonitrile-butadiene-styrene, ethylene vinyl acetate, and polyvinyl chloride; wherein the thermally conductive filler includes at least one of aluminum nitride, boron nitride, silicon carbide, carbon nanotubes, and graphene.
[0083] The filter layer includes a microporous filter membrane.
[0084] Specifically, in this invention, Si single crystal thin film, doped polycrystalline silicon thin film and semi-insulating polycrystalline silicon thin film are surface conductive, while copper foil, aluminum foil, gold foil and nickel-chromium alloy foil are overall conductive.
[0085] Si single-crystal thin films, doped polycrystalline silicon thin films, and semi-insulating polycrystalline silicon thin films can be prepared by magnetron sputtering or vapor deposition processes.
[0086] In another feasible approach, the monolithic conductive film can also be prepared in the following manner:
[0087] Using compounds with highly chemically active components as precursors, these raw materials and conductive materials (such as silver powder, gold powder, and carbon nanotubes) are uniformly mixed in the liquid phase and subjected to hydrolysis and condensation chemical reactions to form a stable, transparent sol system in solution. The sol undergoes slow polymerization between the colloidal particles upon aging, forming a gel with a three-dimensional network structure. The spaces between the gel networks are filled with solvent that has lost its fluidity, thus forming a gel. The gel is then dried and sintered to solidify, preparing materials with molecular and even nanoscale substructures, thereby forming a conductive thin-film colloid, and ultimately realizing a conductive thin film.
[0088] Specifically, when this microfluidic chip is applied to cell sorting and culture, the electromagnetic effect generated between the microelectrode layer 31 and the conductive layer is used to set the corresponding electromagnetic force so that the electromagnetic induction can stay on the target cells, thereby achieving the sorting of target cells. Alternatively, the electromagnetic effect can be used to sense trace biological points in the sample through the microelectrode layer 31 to obtain the state of the target cells. Or, the micro voltage released between the microelectrode and the conductive layer can be used to simulate the electrochemical environment inside the human body for target cell culture.
[0089] Specifically, when the microfluidic chip contains a thermally conductive layer, a thermally conductive layer is set between the first functional layer 1 and the second functional layer 2 and / or between the second functional layer 2 and the third functional layer 3, so that the heat source that the sample can contact is more even. In the application of digital PCR amplification process, the conventional 30 minutes can be reduced to within 10 minutes, which greatly improves the detection efficiency.
[0090] Specifically, when a microfluidic chip contains a filter layer, it can be applied to cell sorting and culture, utilizing the micropores of the microporous membrane to filter out target cells. For example, red blood cells are typically 20 μm in size, while white blood cells are typically around 10 μm in size. Therefore, by utilizing the size difference of the microporous membrane, target cells smaller than 20 μm can be obtained. Alternatively, when mixing multiple reagents on an organ-on-a-chip, the cells can be transferred between each other through the permeation of the membrane pores, resulting in a slow and homogenized mixing and culture process.
[0091] In a preferred embodiment of the present invention, the microchannel 21 of the microfluidic chip includes a detection channel and a reaction channel that are interconnected. The detection channel is connected to the sample outlet 12, and the reaction channel is connected to the sample inlet 11. The reaction channel is provided with a reaction reagent pack, which contains a reagent that reacts with the detection liquid.
[0092] In this embodiment, the size of the microchannel 21 made of thin film is controllable. Therefore, placing a reaction reagent pack that can react with the sample liquid in the microchannel 21 can improve the application range of the microfluidic chip.
[0093] A second aspect of the present invention provides a method for fabricating a microfluidic chip; please refer to [link to relevant documentation]. Figure 4 ,include:
[0094] S10, Provide a first functional layer 1, a second functional layer 2 and a third functional layer 3;
[0095] S20. A sample inlet 11 and a sample outlet 12 are processed on the first functional layer 1;
[0096] S30. Microchannels 21 are fabricated on the second functional layer 2, with the two ends of the microchannels 21 corresponding to the inlet 11 and the outlet 12.
[0097] S40. A microelectrode layer 31 is fabricated on the third functional layer 3. The microelectrode layer 31 has multiple detection ends that are in contact with the microchannel 21.
[0098] S50. The first functional layer 1, the second functional layer 2 and the third functional layer 3 are stacked in sequence, aligned and then pressed and sealed to obtain a microfluidic chip.
[0099] In a preferred embodiment of the present invention, the above-mentioned preparation method for processing the inlet 11 and outlet 12 on the first functional layer 1 specifically includes: etching patterns on the first functional layer 1 by photolithography and die-cutting processes to form the inlet 11 and outlet 12 along the thickness direction of the first functional layer 1.
[0100] In a preferred embodiment of the present invention, the above-mentioned preparation method for processing microchannels 21 on the second functional layer 2 specifically includes: providing a film, and etching patterns on the film through photolithography, die cutting and nanoimprinting processes to form the microchannels 21.
[0101] In a preferred embodiment of the present invention, the above-mentioned preparation method for processing the microelectrode layer 31 on the third functional layer 3 specifically includes: etching the third functional layer 3 to form a pattern corresponding to the microchannel 21 by photolithography and die-cutting processes, and forming the microelectrode layer 31 by metal injection or filling conductive paste on the corresponding pattern.
[0102] The specific steps of the above-mentioned microfluidic chip fabrication method have been described in detail in the relevant embodiments, and will not be elaborated further here.
[0103] In the above embodiments, the descriptions of each embodiment have their own emphasis. For parts not described in detail in a certain embodiment, please refer to the relevant descriptions of other embodiments. Those skilled in the art should also understand that the actions and modules involved in the specification are not necessarily essential to this application. Furthermore, it is understood that the steps in the method of this application embodiment can be adjusted, combined, and deleted according to actual needs, and the modules in the device of this application embodiment can be combined, divided, and deleted according to actual needs.
[0104] The various embodiments of this application have been described above. These descriptions are exemplary and not exhaustive, nor are they limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen to best explain the principles, practical application, or improvement of the technology in the market, or to enable others skilled in the art to understand the embodiments disclosed herein.
Claims
1. A microfluidic chip, characterized in that, It includes a first functional layer, a second functional layer, and a third functional layer that are stacked in sequence; The first functional layer is provided with an inlet and an outlet; The second functional layer includes a thin film layer, on which at least one microchannel is provided, penetrating the thickness direction of the thin film layer, and the microchannel corresponds to the inlet and the outlet respectively; The third functional layer is provided with a microelectrode layer corresponding to the microchannel; The first functional layer, the second functional layer, and the third functional layer are each composed of at least one of a light-transmitting layer, a light-shielding layer, a conductive layer, a heat-conducting layer, and a filter layer. The microelectrode layer includes an electrode layer formed on the third functional layer. The electrode layer extends vertically from the top of the third functional layer toward the bottom of the first functional layer to form an embedded electrode. The top of the third functional layer is one end face of the third functional layer facing the second functional layer, and the bottom of the first functional layer is one end face of the first functional layer facing the second functional layer. The second functional layer has two or more thin film layers, and different microfluidic channel structures are set on each thin film layer. The starting end of the embedded electrode is on the third functional layer, the ending end is on the first functional layer, and it can contact each microfluidic channel at the same time, so that a variety of detection effects can be achieved on the microfluidic chip. The microchannel includes a detection channel and a reaction channel that are interconnected. The detection channel is connected to the sample outlet, and the reaction channel is connected to the sample inlet. The reaction channel is provided with a reaction reagent pack, which contains reagents that react with the detection liquid.
2. The microfluidic chip according to claim 1, characterized in that, The first functional layer, the second functional layer, and the third functional layer are each made of any one of the following materials: plastic, rubber, glass, monocrystalline silicon, and metal.
3. The microfluidic chip according to claim 2, characterized in that, The light-transmitting layer is made of any one of the following materials: polyethylene terephthalate, polyimide, cyclic olefin copolymer, polycarbonate, acrylonitrile-butadiene-styrene, ethylene vinyl acetate, and polyvinyl chloride. The light-shielding layer is made of a composite black masterbatch of any one of the following materials: polyethylene terephthalate, polyimide, cyclic olefin copolymer, polycarbonate, acrylonitrile-butadiene-styrene, ethylene vinyl acetate, and polyvinyl chloride, or it is made of glass by printing with black screen printing ink.
4. The microfluidic chip according to claim 3, characterized in that, The conductive layer is made of any one of the following film materials: Si single crystal thin film, doped polycrystalline silicon thin film, semi-insulating polycrystalline silicon thin film, copper foil, aluminum foil, gold foil, and nickel-chromium alloy foil; The thermally conductive layer is made of any one of the following materials: polyethylene terephthalate, polyimide, cyclic olefin copolymer, polycarbonate, acrylonitrile-butadiene-styrene, ethylene vinyl acetate, and polyvinyl chloride; wherein the thermally conductive filler includes at least one of aluminum nitride, boron nitride, silicon carbide, carbon nanotubes, and graphene. The filter layer includes a microporous filter membrane.
5. A method for fabricating a microfluidic chip as described in any one of claims 1 to 4, characterized in that, The method includes the following steps: It provides a first functional layer, a second functional layer, and a third functional layer; An inlet and an outlet are fabricated on the first functional layer; Microchannels are fabricated on the second functional layer, with the two ends of the microchannels corresponding to the inlet and outlet. A microelectrode layer is fabricated on the third functional layer, and the microelectrode layer has multiple probe ends that are in contact with the microchannel; The first functional layer, the second functional layer, and the third functional layer are stacked sequentially, aligned, and then pressed and sealed to obtain a microfluidic chip.
6. The preparation method according to claim 5, characterized in that, The specific process of fabricating the inlet and outlet on the first functional layer includes: etching patterns on the first functional layer through photolithography and die-cutting processes to form the inlet and outlet along the thickness direction of the first functional layer.
7. The preparation method according to claim 5, characterized in that, The process of fabricating microchannels on the second functional layer specifically includes: providing a film, and etching patterns on the film through photolithography, die cutting, and nanoimprinting processes to form the microchannels.
8. The preparation method according to claim 5, characterized in that, The microelectrode layer is fabricated on the third functional layer by means of: etching a pattern corresponding to the microchannel on the third functional layer by photolithography and die cutting processes, and forming the microelectrode layer by metal injection or filling conductive paste on the corresponding pattern.