Method for realizing thermal bonding of polymer microfluidic chip based on thin film assisted thermal bonding

Abstract

The application discloses a method for realizing thermal bonding of a polymer micro-fluidic chip based on thin film assisted thermal bonding, which comprises the following steps: polymer injection molding is used to prepare a base sheet and a cover sheet of the micro-fluidic chip; after the base sheet and the cover sheet are cleaned, the cleaned base sheet and the cleaned cover sheet are obtained; a layer of thin film is covered on the surface of the cleaned cover sheet to obtain a pretreated cover sheet; the thin film is made of the same material as the base sheet and the cover sheet, and the glass transition temperature of the thin film is lower than that of the cover sheet; the cleaned base sheet and the pretreated cover sheet are aligned on a hot press to complete thermal bonding, and a micro-fluidic chip is obtained; the thermal bonding temperature is higher than the glass transition temperature of the thin film and lower than the glass transition temperature of the cover sheet. The same polymer with different glass transition temperatures is used in the application, and when thermal bonding is performed, the thin film enters a high-elastic state, and the base sheet and the cover sheet are still in a glass state, so that small deformation thermal bonding of the micro-fluidic chip is realized, and the consistency of the bonding interface is ensured.

Description

Technical Field

[0001] This invention relates to the field of microfluidic chip bonding technology, and more specifically to a method for achieving thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding. Background Technology

[0002] Microfluidic chips are novel tools that enable basic biological and chemical analysis in a short time by controlling fluids in a network of microchannels using a single chip; they are also known as laboratory-on-a-chip systems. Materials used to fabricate microfluidic analytical chips include single-crystal silicon, quartz, glass, and organic polymers. Polymer materials are diverse, inexpensive, possess good insulation and light transmittance, are easy to mold, have low mass production costs, and readily yield high aspect ratio microstructures, thus becoming a research hotspot. As a strategic scientific technology, microfluidic chips have broad application prospects in biopharmaceuticals, chemical analysis, and medical testing.

[0003] Bonding is a key technology affecting the quality of microfluidic chips. Currently, bonding methods for microfluidic chips can be broadly classified into two categories: direct bonding and indirect bonding. Direct bonding involves directly bonding the substrate and cover plate, primarily using thermal bonding, ultrasonic bonding, and surface-modified bonding. Indirect bonding utilizes auxiliary adhesives to bond the substrate and cover plate together, mainly using adhesive bonding and solvent bonding. Indirect bonding introduces other substances onto the surface of the microchannels, which may adversely affect the detection results.

[0004] Thermal bonding is a method that achieves molecular-level bonding between the substrate and cover plate of a microfluidic chip without the need for any auxiliary adhesives, relying primarily on the matching of bonding parameters. It is currently the most widely used bonding method due to its advantages of high bonding strength, simple process, and no need to consider biocompatibility and chemical compatibility. However, the bonding pressure and temperature applied during thermal bonding can cause significant deformation of the microchannels in the microfluidic chip.

[0005] To address the significant deformation of microchannels caused by bonding temperature and bonding pressure during thermal bonding, the Chinese University of Hong Kong, in collaboration with Zhou Yongyan et al., employed a spin-coated PDMS (10-25 μm) film as an interlayer to connect the substrate and cap of a PMMA chip, achieving precise, controllable, and low-temperature bonding of microfluidic chips. The bonding process involves: first, injection molding the substrate and cap of the microfluidic chip; then, spin-coating a low-glass transition temperature PDMS film onto the cap; and finally, aligning and thermally bonding it to the substrate containing the microchannels. However, the introduction of different materials between the substrate and cap of the PMMA chip resulted in surface inhomogeneity, leading to low bonding quality and a small bonding area in the final product. Summary of the Invention

[0006] In view of the above-mentioned shortcomings, this invention provides a method for thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding. This method achieves high-strength bonding with minimal deformation by introducing a thin film of the same polymer with a slightly lower glass transition temperature between the substrate and the cover plate. Utilizing the characteristic that the same polymer has different glass transition temperatures, the bonding temperature only needs to reach the lower glass transition temperature of the polymer film, while the substrate and cover plate materials remain in a glassy state with elastic deformation. This enables minimal-deformation thermal bonding of the polymer microfluidic chip while ensuring the consistency of the bonding interface and achieving high-quality thermal bonding.

[0007] To achieve the above objectives, the present invention provides a method for thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding, comprising the following steps:

[0008] Step 1: The substrate and cover plate of the microfluidic chip are prepared by polymer injection molding; wherein the substrate and cover plate are made of the same material and have the same glass transition temperature;

[0009] Step 2: After cleaning the substrate and cover plate of the microfluidic chip, the cleaned substrate and cover plate are obtained.

[0010] Step 3: Cover the cleaned cover sheet with a thin film to obtain a pretreated cover sheet; wherein the thin film is made of the same material as the cover sheet, and the glass transition temperature of the thin film is lower than that of the cover sheet.

[0011] Step 4: Align the cleaned substrate and the pretreated cover plate on a hot press to complete the hot-press bonding and obtain the target microfluidic chip; wherein, the hot-press bonding temperature is higher than the glass transition temperature of the film and lower than the glass transition temperature of the cover plate.

[0012] According to one aspect of the invention, the polymer is an amorphous polymer.

[0013] According to one aspect of the invention, the amorphous polymer includes any one of polycarbonate, cyclic olefin copolymer, polymethyl methacrylate, and polystyrene.

[0014] According to one aspect of the present invention, in step 1, the injection molding is performed using an injection molding machine, specifically by setting the injection molding temperature of the injection molding machine to the melt temperature of the polymer.

[0015] According to one aspect of the invention, the injection molding rate is 20-45 cm. 3 / s, mold temperature is 120℃, holding pressure is 120~180MPa, holding time is 5~10s.

[0016] According to one aspect of the invention, in step 2, the cleaning process consists of three cleaning cycles.

[0017] According to one aspect of the present invention, the cleaning process specifically consists of ultrasonication in a deionized water bath at 60°C for 5 minutes, ultrasonication in a deionized water bath at 45°C for 5 minutes, and ultrasonication in a deionized water bath at 45°C for 2 minutes.

[0018] According to one aspect of the invention, in step 3, the glass transition temperature of the film being lower than that of the cover sheet is specifically achieved by adding a plasticizer to the polymer or by directly purchasing a corresponding polymer with a lower glass transition temperature than the polymer.

[0019] According to one aspect of the present invention, in step 3, the covering is specifically spin coating, which is achieved using a spin coater, wherein the spin coating speed is 1500-3000 rpm / min and the spin coating time is 30-60 s.

[0020] According to one aspect of the present invention, in step 4, the pressure of the hot-press bonding is 0.5 to 3 MPa, and the bonding time is 150 to 300 s.

[0021] The beneficial effects of this invention are:

[0022] (1) By introducing a thin film with a low glass transition temperature, microfluidic chips can achieve small deformation bonding at low temperatures;

[0023] (2) The thin film material with a low glass transition temperature is the same as the substrate and cover plate material, which maintains surface uniformity and ensures bonding quality;

[0024] (3) Polymer microfluidic chips can be prepared by injection molding combined with hot pressing, which can achieve high quality, large-scale and low-cost manufacturing.

[0025] This invention achieves high-strength bonding with minimal deformation by introducing a thin film of the same polymer with a slightly lower glass transition temperature between the substrate and the cover plate. Utilizing the characteristic that the same polymer has different glass transition temperatures, the bonding temperature only needs to reach the lower glass transition temperature of the polymer film, while the substrate and cover plate materials remain in a glassy state with elastic deformation. This enables minimal-deformation thermal bonding of polymer microfluidic chips while ensuring the consistency of the bonding interface, achieving high-quality thermal bonding, and possessing significant research and application value.

[0026] The following will further elaborate on the specific implementation methods. Attached Figure Description

[0027] Figure 1This is a process flow diagram of the method for achieving thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding according to the present invention.

[0028] Figure 2 This is a schematic diagram of the thin-film assisted thermo-press bonding described in this invention;

[0029] Figure 3 This is a schematic diagram of the microfluidic chip described in an embodiment of the present invention.

[0030] Explanation of reference numerals in the attached figures:

[0031] 1. Cover sheet; 2. Thin film; 3. Substrate; 4. Microchannel; 5. Inlet; 6. Outlet. Detailed Implementation

[0032] To make the present invention easier to understand, specific embodiments are described below to further illustrate the invention. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise defined, the technical terms used below have the same meaning as understood by those skilled in the art; unless otherwise specified, the raw materials and reagents involved herein can be purchased commercially or obtained by known methods.

[0033] Current thermal bonding technology for microfluidic chips introduces different materials between the substrate and cover plate of the PMMA chip, resulting in surface inhomogeneity and ultimately low bonding quality and a small bonding area in the finished product.

[0034] To address the aforementioned problems, this application provides a method for thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding, such as... Figure 1-2 As shown, it includes the following steps:

[0035] Step 1: The substrate 3 and cover plate 1 of the microfluidic chip are prepared by polymer injection molding; wherein the substrate 3 and cover plate 1 are made of the same material and have the same glass transition temperature;

[0036] It should be noted that the polymer is an amorphous polymer.

[0037] For example, the amorphous polymer includes any one of polycarbonate (PC), cyclic olefin copolymer (COC), polymethyl methacrylate (PMMA), and polystyrene (PS).

[0038] Preferably, in step 1, the injection molding is achieved using an injection molding machine, specifically by setting the injection molding temperature of the injection molding machine to the melt temperature of the polymer.

[0039] Preferably, the injection rate of the injection molding is 20-45 cm. 3 / s, mold temperature is 120℃, holding pressure is 120~180MPa, holding time is 5~10s.

[0040] Step 2: After cleaning the substrate 3 and cover plate 1 of the microfluidic chip, the cleaned substrate 3 and cover plate 1 are obtained.

[0041] Preferably, in step 2, the cleaning process involves three cleaning cycles; specifically, the deionized water is replaced three times. More preferably, the cleaning process involves ultrasonication in a deionized water bath at 60°C for 5 minutes, ultrasonication in a deionized water bath at 45°C for 5 minutes, and ultrasonication in a deionized water bath at 45°C for 2 minutes.

[0042] Step 3: Cover the cleaned cover plate 1 with a thin film 2 to obtain a pretreated cover plate; wherein, the thin film 2 is made of the same material as the cover plate 1, and the glass transition temperature of the thin film 2 is lower than that of the cover plate 1.

[0043] Preferably, in step 3, the glass transition temperature of the thin film 2 is lower than that of the cover plate 1. This is achieved by adding a plasticizer to the polymer and spin-coating it onto the cover plate, or by directly purchasing a corresponding polymer with a lower glass transition temperature than the polymer, cutting it into a certain shape, and placing it directly between the substrate and the cover plate to complete the bonding.

[0044] Preferably, the mass ratio of the polymer monomer to the plasticizer is 1:0.2-0.45.

[0045] For example, the plasticizer may be dioctyl phthalate (DOP), [C4MIM][PF6], dibutyl phthalate, etc. Dioctyl phthalate (DOP) is preferred.

[0046] It should be noted that by purchasing a polymer with a lower glass transition temperature than the polymer mentioned above, and by purchasing a film material with a low molecular weight or good molecular chain flexibility, the glass transition temperature will be low.

[0047] Preferably, in step 3, the spin coating is performed using a spin coater, with a spin coating speed of 1500–3000 rpm / min and a spin coating time of 30–60 s.

[0048] Step 4: Align the cleaned substrate 4 and the pretreated cover plate on a hot press to complete the hot-press bonding and obtain the target microfluidic chip; wherein, the hot-press bonding temperature is higher than the glass transition temperature of the film and lower than the glass transition temperature of the cover plate.

[0049] Preferably, in step 4, the pressure of the hot-press bonding is 0.5 to 3 MPa, and the bonding time is 150 to 300 s.

[0050] In this application, the hot-press bonding was performed using a hot-press bonding experimental platform independently built by our research group. The hot-press bonding process is as follows:

[0051] 1) Chip alignment: The chip is aligned and placed within the bonding cavity;

[0052] 2) Mold closing: The linear motor controls the lower moving plate of the bonding platform to drive the mold closing, keeping the chip tightly attached under slight force;

[0053] 3) Basic mold temperature control: Activate the basic mold temperature control circuit, and the heating rod heats the mold to bring the cavity temperature to the bonding temperature;

[0054] 4) Loading pressure: Set the bonding pressure, and the pressure cabinet controls the plunger motor to apply pressure to the bonding die;

[0055] 5) Demolding after bonding: After the bonding time is completed, heating is stopped, the mold is opened for cooling, and the chip is removed from the mold.

[0056] In some embodiments of this application, the microfluidic chip of this application is as follows: Figure 3 As shown, it includes a substrate 1, a thin film 2 and a cover plate 3. The substrate 1 is provided with a microchannel 4 and an inlet 5 and an outlet 6 at both ends of the microchannel 4.

[0057] The mechanism of this invention is as follows: by introducing a thin film of the same polymer with a slightly lower glass transition temperature between the substrate and the cover plate, high-strength bonding with small deformation is achieved. Utilizing the characteristic that the same polymer has different glass transition temperatures, the bonding temperature only needs to reach the lower glass transition temperature of the polymer film, while the substrate and cover plate materials remain in a glassy state with elastic deformation. This achieves small-deformation thermal bonding of the polymer microfluidic chip, while ensuring the consistency of the bonding interface and achieving high-quality thermal bonding.

[0058] The present application is described below with reference to specific embodiments and comparative examples.

[0059] Example 1

[0060] This embodiment provides a method for achieving thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding, including the following steps:

[0061] Step 1: Injection mold PMMA to prepare the substrate and cover plate of the microfluidic chip;

[0062] Specifically, the width of the microchannels on the substrate is 200 μm. The injection molding is achieved on a German Arburg 370S precision injection molding machine through injection, pressure holding, cooling, and demolding. Specifically, the injection molding machine is set to the PMMA melt temperature of 250–270°C; the injection rate is 20–45 cm⁻¹. 3 / s, mold temperature is 80℃, holding pressure is 120~180MPa, holding time is 5~10s.

[0063] Step 2: After cleaning the substrate and cover plate of the microfluidic chip, the cleaned substrate and cover plate are obtained.

[0064] Specifically, the substrate and cover plate were cleaned using an ultrasonic cleaning agent, and the cleaning was performed three times in total. The cleaning process consisted of ultrasonic treatment in a deionized water bath at 60°C for 5 minutes, ultrasonic treatment in a deionized water bath at 45°C for 5 minutes, and ultrasonic treatment in a deionized water bath at 45°C for 2 minutes.

[0065] Step 3: Spin-coat a thin film onto the cleaned cover plate surface to obtain a pretreated cover plate; wherein the film is made of the same material as the cover plate, and the glass transition temperature of the film is lower than that of the cover plate.

[0066] Specifically, the PMMA material is first dissolved in acetone, then dioctyl phthalate (DOP) with a mass ratio of 0.35 relative to the PMMA monomer is added and stirred evenly. The spin coater is then used at a speed of 3000 rpm / min for 60 seconds.

[0067] It should be noted that in this step, the glass transition temperatures of the microfluidic chip polymer material PMMA (substrate and cover plate) and the same polymer PMMA thin film material were determined to be 104.9℃ and 90℃, respectively, using differential scanning calorimetry (DSC).

[0068] Step 4: Align the cleaned substrate and the pretreated cover plate on a hot press to complete the hot press bonding and obtain the target microfluidic chip; wherein, the temperature of the hot press bonding (95°C) is higher than the glass transition temperature of the film and lower than the glass transition temperature of the cover plate; the pressure of the hot press bonding is 1.5 MPa and the bonding time is 240 s.

[0069] Example 2

[0070] This embodiment provides a method for achieving thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding, including the following steps:

[0071] Step 1: The substrate and cover plate of the microfluidic chip are prepared by injection molding of PC;

[0072] Specifically, the width of the microchannels on the substrate is 200 μm. The injection molding is achieved on a German Arburg 370S precision injection molding machine through injection, pressure holding, cooling, and demolding. Specifically, the injection molding machine is set to the PC melt temperature of 260-280℃; the injection rate is 20-45 cm / s. 3 / s, mold temperature is 120℃, holding pressure is 120~180MPa, holding time is 5~10s.

[0073] Step 2: After cleaning the substrate and cover plate of the microfluidic chip, the cleaned substrate and cover plate are obtained.

[0074] Specifically, the substrate and cover plate were cleaned using an ultrasonic cleaning agent, and the cleaning was performed three times in total. The cleaning process consisted of ultrasonic treatment in a deionized water bath at 60°C for 5 minutes, ultrasonic treatment in a deionized water bath at 45°C for 5 minutes, and ultrasonic treatment in a deionized water bath at 45°C for 2 minutes.

[0075] Step 3: Cover the cleaned cover sheet with a thin film to obtain a pretreated cover sheet; wherein the thin film is made of the same material as the cover sheet, and the glass transition temperature of the thin film is lower than that of the cover sheet.

[0076] Specifically, PC is first slightly dissolved in acetone, then dioctyl phthalate (DOP) with a mass ratio of 0.35 relative to the PC monomer is added and stirred evenly. After centrifugation, the upper transparent liquid is taken and spin-coated at a speed of 3000 rpm / min for 60 s.

[0077] It should be noted that in this step, differential scanning calorimetry (DSC) was used to determine the glass transition temperatures of the polymer material (substrate and cover plate) and the same polymer film material of the microfluidic chip, which were 151℃ and 135℃, respectively.

[0078] Step 4: Align the cleaned substrate and the pretreated cover plate on a hot press to complete the hot press bonding and obtain the target microfluidic chip; wherein, the temperature of the hot press bonding (140°C) is higher than the glass transition temperature of the film and lower than the glass transition temperature of the cover plate; the pressure of the hot press bonding is 2MPa and the bonding time is 240s.

[0079] Example 3

[0080] This embodiment provides a method for achieving thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding, including the following steps:

[0081] Step 1: The substrate and cover plate of the microfluidic chip are prepared by injection molding of PC;

[0082] Specifically, the width of the microchannels on the substrate is 200 μm. The injection molding is achieved on a German Arburg 370S precision injection molding machine through injection, pressure holding, cooling, and demolding. Specifically, the injection molding machine is set to the PC melt temperature of 260-280℃; the injection rate is 20-45 cm / s. 3 / s, mold temperature is 120℃, holding pressure is 120~180MPa, holding time is 5~10s.

[0083] Step 2: After cleaning the substrate and cover plate of the microfluidic chip, the cleaned substrate and cover plate are obtained.

[0084] Specifically, the substrate and cover plate were cleaned using an ultrasonic cleaning agent, and the cleaning was performed three times in total. The cleaning process consisted of ultrasonic treatment in a deionized water bath at 60°C for 5 minutes, ultrasonic treatment in a deionized water bath at 45°C for 5 minutes, and ultrasonic treatment in a deionized water bath at 45°C for 2 minutes.

[0085] Step 3: Cover the cleaned cover sheet and substrate with a purchased film; wherein the film is made of the same material as the cover sheet, and the glass transition temperature of the film is lower than that of the cover sheet.

[0086] It should be noted that in this step, differential scanning calorimetry (DSC) was used to determine the glass transition temperatures of the polymer material (substrate and cover plate) and the same polymer film material of the microfluidic chip, which were 151℃ and 143℃, respectively.

[0087] It should be noted that the film used in this step is polycarbonate film from Dongguan Bohai Plastic Film Co., Ltd., with the product number PC10.

[0088] Step 3: Align the cleaned substrate, film, and cover plate three-layer structure on a hot press to complete the hot press bonding and obtain the target microfluidic chip; wherein, the hot press bonding temperature (140°C) is higher than the glass transition temperature of the film and lower than the glass transition temperature of the cover plate; the hot press bonding pressure is 2MPa and the bonding time is 240s.

[0089] Comparative Example 1

[0090] The difference between this comparative example and Example 1 is that step 3 is different. In this comparative example, step 3 is a non-spin-coated thin film, and the hot-press bonding temperature is 105°C (slightly higher than the glass transition temperature of the substrate and cover plate). The other steps are the same as in Example 1.

[0091] Results detection and analysis

[0092] The microfluidic chips prepared in Example 1 and Comparative Example 1 were subjected to relevant tests. Ultra-depth-of-field microscopy measurements revealed that the deformation of the microchannel in Example 1 occurred in its height, with a deformation amount of 5.7%. In Comparative Example 1, the deformation in height and width reached 10.5% and 14%, respectively, indicating that the bonding deformation of this application is small. The bonding strength of the microfluidic chips prepared in Example 1 and Comparative Example 1 was tested using a CMT 4204 tensile testing machine, and the strengths were 0.98 MPa and 0.45 MPa, respectively, indicating that the bonding method of this application has higher strength.

[0093] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A method for thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding, characterized in that, Includes the following steps: Step 1: The substrate and cover plate of the microfluidic chip are prepared by polymer injection molding; wherein the substrate and cover plate are made of polymers with the same material and the same glass transition temperature; Step 2: After cleaning the substrate and cover plate of the microfluidic chip, a cleaned substrate and a cleaned cover plate are obtained; Step 3: Cover the cleaned cover sheet with a thin film to obtain a pretreated cover sheet; wherein, the thin film is made of the same material as the cover sheet, and the glass transition temperature of the thin film is lower than that of the cover sheet; the lower glass transition temperature of the thin film is achieved by adding a plasticizer to the polymer or by directly purchasing a corresponding polymer with a lower glass transition temperature than the polymer; the covering is specifically achieved by spin coating, which is done using a spin coater, with a spin coating speed of 1500~3000 rpm / min and a spin coating time of 30~60s; Step 4: Align the cleaned substrate and the pretreated cover plate on a hot press to complete the hot-press bonding and obtain the target microfluidic chip; wherein, the hot-press bonding temperature is higher than the glass transition temperature of the film and lower than the glass transition temperature of the cover plate; the hot-press bonding pressure is 0.5~3MPa and the bonding time is 150~300s.

2. The method for thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding according to claim 1, characterized in that, The polymer is an amorphous polymer.

3. The method for thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding according to claim 2, characterized in that, The amorphous polymer includes any one of polycarbonate, cyclic olefin copolymer, polymethyl methacrylate, and polystyrene.

4. The method for thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding according to claim 1, characterized in that, In step 1, the injection molding is achieved using an injection molding machine, specifically by setting the injection molding temperature of the injection molding machine to the melt temperature of the polymer.

5. The method for thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding according to claim 4, characterized in that, The injection rate for injection molding is 20~45cm. 3 / s, mold temperature is 120℃, holding pressure is 120~180MPa, holding time is 5~10s.

6. The method for thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding according to claim 1, characterized in that, In step 2, the cleaning process involves three cleaning cycles.

7. The method for thermal bonding of polymer microfluidic chips based on thin-film assisted thermal bonding according to claim 6, characterized in that, The cleaning process specifically involves ultrasonication in a deionized water bath at 60°C for 5 minutes, ultrasonication in a deionized water bath at 45°C for 5 minutes, and ultrasonication in a deionized water bath at 45°C for 2 minutes.

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