PMMA microfluidic chip packaging method and PMMA microfluidic chip

Abstract

The application discloses a PMMA micro-fluidic chip packaging method, mainly comprising the following steps: providing a PMMA micro-fluidic chip to be packaged; adding phase change material into a micro-fluid channel of a chip bottom plate after the phase change material is heated to a molten state; covering a layer of solvent on a bonding surface of the chip bottom plate after the phase change material is cooled and solidified; aligning a chip cover plate with the chip bottom plate and combining the chip cover plate with the chip bottom plate, the solvent infiltrating the bonding surfaces of the chip bottom plate and the chip cover plate and forming a liquid bridge between the chip bottom plate and the chip cover plate, the chip bottom plate and the chip cover plate being automatically aligned according to a contour by a horizontal directional component force of the liquid bridge force; and after standing until the bonding is completed, heating the micro-fluidic chip to melt and blow out the phase change material in the micro-fluid channel, and completing the packaging. Furthermore, the application also provides a PMMA micro-fluidic chip formed by the packaging method. The application realizes the packaging of the PMMA micro-fluidic chip by one-step method, does not need to rely on external expensive equipment, is simple to operate, has high alignment precision and good bonding quality.

Description

Technical Field

[0001] This invention belongs to the field of microfluidic chip packaging technology, specifically relating to a PMMA microfluidic chip packaging method and a PMMA microfluidic chip packaged using this method. Background Technology

[0002] Microfluidics is a technology that uses micron and submicron channels to process or manipulate tiny fluids. Compared with traditional analytical methods, it has significant advantages such as high speed, low reagent consumption, high throughput and high degree of system integration. It has already shown great potential in single-cell analysis, food inspection, drug detection, nanoparticle synthesis, high-throughput drug screening and in vitro physiological and pathological model construction (i.e. organ-on-a-chip).

[0003] While significant progress has been made in the fabrication process and applications of microfluidic chips across various fields, the packaging technology for microfluidic chips still faces numerous challenges. Microfluidic chip packaging primarily involves two processes: alignment and bonding. Current alignment methods for microfluidic chips mainly rely on alignment devices built from precision mechanical position adjustment mechanisms, visual feedback systems, and optical aiming systems. However, these methods suffer from drawbacks such as expensive equipment, complex operation, poor repeatability, and low efficiency.

[0004] Thermoplastics have attracted widespread attention in the manufacture of microfluidic chips due to their advantages in industrial applications, such as low cost and rapid bonding methods. Among various thermoplastics, polymethyl methacrylate (PMMA) has become an essential thermoplastic for microfluidic chip manufacturing due to its cost-effectiveness, optical transparency, and biocompatibility. Currently, the commonly used bonding methods for PMMA chips are hot-press bonding and solvent bonding. Hot-press bonding requires the use of bulky presses and heaters, which may lead to deformation of the microchannels. Solvent bonding mainly utilizes the dissolution and diffusion of solvent molecules on the polymer to re-crosslink the polymer chains at the interface, thereby achieving high-strength bonding. However, since strong solvents can dissolve PMMA, microchannel blockage is a common defect of solvent bonding.

[0005] Furthermore, the alignment and bonding of current microfluidic chips are two separate operations. In chip packaging, this not only increases the complexity of the process but also hinders efficiency. Therefore, developing an alignment and bonding method that is simple to operate, highly repeatable, precise, and efficient is of great significance for accelerating the development of the microfluidic industry. Summary of the Invention

[0006] To address the aforementioned problems, this invention proposes a PMMA microfluidic chip packaging method, aiming to achieve spontaneous alignment and bonding of the chip using the liquid bridge principle and a one-step solvent method. Furthermore, this invention also provides a PMMA microfluidic chip formed using this packaging method.

[0007] The first aspect of this invention is to provide a PMMA microfluidic chip packaging method, which mainly includes the following steps:

[0008] A PMMA microfluidic chip to be packaged is provided. The PMMA microfluidic chip includes a chip cover plate and a chip base plate for use. The bonding surface of the chip base plate is provided with microfluidic channels and a first through hole and a second through hole that communicate with both ends of the microfluidic channels and penetrate the chip base plate.

[0009] The phase change material is heated to a molten state and then dropped into the microfluidic channels of the chip substrate, completely filling the microfluidic channels.

[0010] After the phase change material cools and solidifies, a layer of solvent is applied to the bonding surface of the chip substrate, excluding the microfluidic channels; the solvent can bond the PMMA chip and does not react with the phase change material.

[0011] The chip cover plate is aligned and closed with the chip substrate, and the solvent wets the bonding surfaces of the chip substrate and the chip cover plate and forms a liquid bridge between them;

[0012] When the chip cover is lifted vertically, the chip base plate overcomes its own gravity and adheres to the bottom of the chip cover by the vertical component of the liquid bridge force, and automatically aligns with the chip cover according to the contour by the horizontal component of the liquid bridge force.

[0013] After standing until the solvent has fully reacted, the chip cover plate and the chip substrate are tightly bonded together, and the bonding is completed.

[0014] The microfluidic chip is heated until the phase change material in the microfluidic channel melts, and then the molten phase change material in the microfluidic channel is blown out through the first and second through holes, thus completing the encapsulation of the microfluidic chip.

[0015] As an alternative, the phase change material is any one of sodium thiosulfate, agar, paraffin, and polycaprolactone.

[0016] As an alternative, the solvent is selected from any one of toluene, dichloromethane, acetic acid, dichloroethane, methane cyanide, acetone, and isopropanol.

[0017] As an alternative, the thickness of the solvent covering the bonding surface of the chip substrate is 100-200 μm.

[0018] As an alternative, the melting point of the phase change material is in the range of 30-100℃.

[0019] As an alternative, the heating temperature is greater than the melting point of the phase change material but less than 115 degrees Celsius.

[0020] As an alternative, the PMMA microfluidic chip packaging method further includes: after completely filling the microfluidic channel with molten phase change material, scraping off excess phase change material from the chip substrate.

[0021] As an alternative, the PMMA microfluidic chip packaging method further includes: blowing out the molten phase change material in the microfluidic channel, and then cleaning and drying the microfluidic channel.

[0022] As an alternative, the PMMA microfluidic chip packaging method also includes improving bonding efficiency during the bonding process by increasing the ambient temperature, microwave treatment, or ultraviolet light treatment.

[0023] A second aspect of the present invention is to provide a PMMA microfluidic chip, which is packaged using the method described in the first aspect of the present invention or any alternative embodiment thereof.

[0024] This invention is based on the liquid bridge principle and uses solvent assistance to complete the two processes of self-alignment and bonding. It achieves the packaging of PMMA microfluidic chips in one step without the need for expensive external equipment. It is simple to operate, has high alignment accuracy and good bonding quality, and can meet the packaging requirements of most commonly used chips. Attached Figure Description

[0025] Figure 1 A schematic diagram of the PMMA chip structure;

[0026] Figure 2 This is a schematic diagram of the bonding process;

[0027] Figure labels: 1-Suspension plate, 2-Chip cover plate; 21-Cross mark, 3-Solvent, 4-Chip substrate; 41-Cross mark; 42-Inlet; 43-Microfluidic channel; 44-Outlet, 5-Support device, 6-Suspension frame. Detailed Implementation

[0028] The technical solution of the present invention will be clearly and completely described below with specific embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0029] Combination Figure 1As shown, it can be understood that a PMMA microfluidic chip typically consists of a chip cover plate 2 and a chip base plate 4 used in conjunction. The chip base plate 4 is provided with microfluidic channels 43 and inlets 42 and outlets 44 communicating with both ends of the microfluidic channels 43. Specifically, the inlets 42 and outlets 44 are through holes penetrating the chip base plate 4. This invention does not impose specific limitations on the structure of the microfluidic chip itself and its microfluidic channels 43; the specific structure depends on the actual function.

[0030] For ease of description, in this embodiment, the bonding surfaces of both the chip cover plate 2 and the chip substrate 4 are defined as the front side, and the non-bonding surfaces opposite to them are defined as the back side. The front sides of the chip cover plate 2 and the chip substrate 4 are arranged opposite each other, and the microfluidic chip is packaged after one-step alignment and bonding.

[0031] Combination Figure 2 As shown in the embodiment, a PMMA microfluidic chip packaging method is given, which mainly includes the following steps:

[0032] Step 1: Heat the selected phase change material to melt, take a small amount of molten liquid (i.e., molten phase change material) and drop it onto the front of the chip substrate 4 of the PMMA microfluidic chip to be packaged (hereinafter referred to as "PMMA chip"), completely filling the microfluidic channel 43. While it is hot, use a plastic scraper to remove the excess phase change material from the surface of the chip substrate 4, so that the phase change material just fills the microfluidic channel 43 and is flush with the surface of the chip substrate 4.

[0033] Understandably, incomplete filling of the phase change material can easily lead to deformation of the microfluidic channel 43, and if it extends above the microfluidic channel 43, leakage may occur after packaging due to inadequate sealing. At the same time, there should be no residual phase change material in other areas of the chip substrate 4, otherwise it will affect the optical transmittance of the PMMA chip.

[0034] Here, phase change materials mainly refer to materials that can undergo a solid-liquid phase transition within the temperature range of 0-100℃. Typically, they are solid at low temperatures (e.g., 0-90℃) and liquid at high temperatures (e.g., 30-100℃). Specific examples of phase change materials include sodium thiosulfate (phase change temperature 48℃), agar (phase change temperature 75-90℃), paraffin wax (phase change temperature 50-70℃), and polycaprolactone (phase change temperature 59℃).

[0035] Step 2: After the phase change material cools and solidifies, place the chip substrate 4 horizontally on the support device 5 with the front side facing up; then drop a certain amount of solvent 3 onto the front side of the chip substrate 4. The solvent 3 should completely cover the area on the front side of the chip substrate 4 except for the microfluidic channel 43.

[0036] The choice of solvent should meet at least the following three requirements: 1) it should be wettable to the chip material; 2) it should be able to bond the PMMA chip; and 3) it should not react with the phase change material. Specifically, solvents such as toluene, dichloromethane, acetic acid, dichloroethane, methane cyanide, acetone, and isopropanol can be used.

[0037] The amount of solvent added depends on the area of ​​the front side of the chip substrate 4 (excluding the area of ​​the microfluidic channel 43). Considering the effect of liquid bridge formation, the thickness of the solvent per unit area should ideally be controlled within the range of 100-200 μm.

[0038] Step 3: Secure the back of the chip cover plate 2 to the mounting surface at the bottom of the suspension plate 1 using double-sided tape. Lower the suspension plate 1 so that the chip cover plate 2 also slowly descends until it aligns with the chip substrate 4. At this point, the solvent on the front of the chip substrate 4 wets the front of the chip cover plate 2, forming a liquid bridge between them. Under the force of the liquid bridge, the bonding surfaces of the chip substrate 4 and the chip cover plate 2 adhere together. Then, lift the suspension plate 1. The chip substrate 4 will be lifted along with the chip cover plate 2. Place the suspension plate 1 on the suspension bracket 6, keeping the chip substrate 4 and the chip cover plate 2 suspended. During the lifting process, ensure that the chip substrate 4 is horizontal and friction-free. This can be achieved by lifting the chip cover plate 2 vertically.

[0039] It should be noted that, in this process, the present invention utilizes the surface tension of the liquid. The vertical component of the liquid bridge force formed between the chip cover plate 2 and the chip base plate 4 enables the chip base plate 4 to overcome its own gravity and adhere to the bottom of the chip cover plate 2. The horizontal component of the liquid bridge force enables the chip base plate 2 and the chip cover plate 4 to automatically align according to the contour.

[0040] Step 4: Let it stand for a period of time (usually 1-5 hours) until the solvent has fully acted, and the chip cover plate 2 and the chip substrate 4 will be tightly bonded together, and the bonding will be completed.

[0041] Understandably, this method belongs to solvent bonding. During the bonding process, the thermal motion of polymer chains on the surface of the chip material in the solvent can be accelerated by increasing the ambient temperature, microwave treatment, ultraviolet light treatment, etc., thereby shortening the reaction time, improving bonding efficiency, and increasing bonding strength.

[0042] Step 5: After bonding is completed, heat the microfluidic chip until the phase change material in the microfluidic channel 43 melts. Then, blow compressed air into the microfluidic channel 43 from the chip inlet 42. The compressed air pushes the molten phase change material in the microfluidic channel 43 out from the outlet 44. Finally, wash the microfluidic channel 43 with clean water and dry it. This completes the encapsulation of the microfluidic chip.

[0043] In particular, the heating temperatures in steps one and five should be greater than the melting point of the phase change material and less than the glass transition temperature of PMMA (115°C), depending on the selected phase change material.

[0044] Combination Figure 1 As shown, the support device 5 is required to be horizontal and flat. It can be a horizontal tabletop or a support column with a flat upper surface placed on a horizontal tabletop. A support column is preferred to prevent solvent from flowing between the chip substrate 4 and the support device 5, thus avoiding liquid bridging and adsorption of the chip substrate 4. The upper surface area of ​​the support device 5 should be greater than 1 cm². 2 This ensures the chip can be placed stably and horizontally. The suspension plate 1 is a horizontally placed rigid plate, which can be made of glass, wood, metal, plastic, etc. Considering that glass is both transparent and hard, facilitating observation during operation, glass is preferred for the suspension plate 1. The suspension frame 6 works with the suspension plate 1 to suspend the chip, and can be a frame structure with a central cavity. The suspension plate 1 is placed on top of the suspension frame 6, and the chip base plate 4 and chip cover plate 2 are placed within the cavity of the suspension frame 6. Alternatively, a beaker can be used to support the suspension plate 1. It should be noted that this invention does not impose specific limitations on the composition and structural characteristics of the above-mentioned auxiliary device. Other devices can be combined, an integrated device can be used, or automated operation can be employed, as long as it can complete the PMMA chip packaging.

[0045] In summary, this invention addresses the problems of expensive equipment, complex operation, poor repeatability, low efficiency, and incompatible bonding processes required for PMMA microfluidic chip alignment. It proposes a PMMA microfluidic chip packaging method that utilizes the liquid bridge alignment principle to achieve PMMA microfluidic chip alignment and bonding in a one-step process. Furthermore, this method does not require expensive equipment, is simple to operate, offers high alignment accuracy, and produces high-quality bonding.

[0046] Based on the above implementation scheme, two specific application examples of PMMA microfluidic chip packaging are given below:

[0047] Application Example 1:

[0048] First, a PMMA microfluidic chip is machined using a CNC milling machine, combined with... Figure 2As shown, both the chip cover plate 2 and the chip substrate 4 have dimensions of 35mm (length) × 25mm (width) × 2mm (thickness). The chip substrate 4 has a microfluidic channel 43 measuring 500um (width) × 500um (depth) × 15mm (length) and two through holes with a diameter of 2mm. The through holes penetrate the front and back sides of the chip substrate 4, are located at both ends of the microfluidic channel 43 and communicate with it, serving as the inlet 42 and outlet 44 of the microfluidic channel 43, respectively. The chip cover plate 2 and the chip substrate 4 have two crosshair marks 21 and 41 at corresponding positions, respectively. The crosshair marks have dimensions of 1mm (length) × 1mm (width) × 0.05mm (depth), and are mainly used for reference alignment accuracy.

[0049] Then, agar powder and water are mixed at a mass ratio of 2:100. After mixing evenly, the mixture is heated at 95°C for 10 minutes. Once the agar powder is completely dissolved, a small amount is dropped onto the front side of the chip substrate 4 to completely fill the microfluidic channel 43. Then, excess agar on the surface is removed with a plastic scraper.

[0050] After the agar cools and solidifies, 120 μL of toluene is dropped onto the front side of the chip substrate 4, with a thickness of approximately 137 μm. Then, the chip cover plate 2 is aligned with the chip substrate 4 and placed on the chip substrate 4, allowing the toluene to completely wet the surfaces of both plates. Next, the chip cover plate 2 is lifted vertically, and the chip substrate 4, under the force of the liquid bridge, overcomes its own gravity and adheres to the bottom of the chip cover plate 2, automatically aligning with the chip cover plate 2. After standing for 5 hours, the solvent toluene completely evaporates, and the self-alignment bonding is completed.

[0051] Finally, the bonded PMMA microfluidic chip is heated to 95°C to melt the agar, and compressed gas is used to blow the agar out of the microfluidic channel. After cleaning and drying, the encapsulation is completed.

[0052] Application Example 2:

[0053] First, the PMMA microfluidic chip is machined using a CNC milling machine. The chip cover plate 2 and chip base plate 4 have dimensions of 35mm (length) × 25mm (width) × 3mm (thickness). The chip base plate 4 has a microfluidic channel 43 with dimensions of 300um (width) × 300um (depth) × 15mm (length) and two through holes with a diameter of 1mm. The through holes penetrate the front and back sides of the chip base plate 4, are located at both ends of the microfluidic channel 43 and are connected to it, serving as the inlet 42 and outlet 44 of the microfluidic channel 43, respectively. The chip cover plate 2 and chip base plate 4 have two cross marks 21 and 41 at corresponding positions, with dimensions of 1mm (length) × 1mm (width) × 0.05mm (depth), mainly used for reference alignment accuracy.

[0054] Heat the paraffin wax at 80°C for 10 minutes until it is completely melted. Then, take a small amount and drop it onto the front side of the chip substrate 4 to completely fill the microfluidic channel 43. Finally, use a plastic scraper to remove the excess paraffin wax from the surface.

[0055] After the paraffin has cooled and solidified, 100 μL of acetic acid is dropped onto the front side of the chip substrate 4, making the thickness of the chip substrate 4 approximately 114 μm. Then, the chip cover plate 2 is aligned with the chip substrate 4 and placed on the chip substrate 4, allowing toluene to completely wet the surfaces of both plates. Then, the chip cover plate 2 is lifted vertically, and the chip substrate 4, under the force of the liquid bridge, overcomes its own gravity and adheres to the bottom of the chip cover plate 2 and automatically aligns with the chip cover plate 2. After standing for 1 hour, the solvent acetic acid completely evaporates, and the self-alignment bonding is completed.

[0056] Finally, the bonded PMMA microfluidic chip is heated to 80°C to melt the paraffin wax. Compressed gas is used to blow the paraffin wax out of the microfluidic channel, and the chip is cleaned and dried to complete the encapsulation.

[0057] Finally, it should be noted that although the embodiments of the present invention have been described above in conjunction with the accompanying drawings, the present invention is not limited to the specific embodiments and application fields described above. The specific embodiments described above are merely illustrative and instructive, and not restrictive. Those skilled in the art, guided by this specification, can make many other forms without departing from the scope of protection of the claims of the present invention, and all of these are within the scope of protection of the present invention.

Claims

1. A PMMA microfluidic chip packaging method, characterized in that, Includes the following steps: A PMMA microfluidic chip to be packaged is provided. The PMMA microfluidic chip includes a chip cover plate and a chip base plate for use. The bonding surface of the chip base plate is provided with microfluidic channels and a first through hole and a second through hole that communicate with both ends of the microfluidic channels and penetrate the chip base plate. The phase change material is heated to a molten state and then dropped into the microfluidic channels of the chip substrate, completely filling the microfluidic channels. After the phase change material cools and solidifies, a layer of solvent is applied to the bonding surface of the chip substrate, excluding the microfluidic channels; the solvent can bond the PMMA chip and does not react with the phase change material. The chip cover plate is aligned and closed with the chip substrate, and the solvent wets the bonding surfaces of the chip substrate and the chip cover plate and forms a liquid bridge between them; When the chip cover is lifted vertically, the chip base plate overcomes its own gravity and adheres to the bottom of the chip cover by the vertical component of the liquid bridge force, and automatically aligns with the chip cover according to the contour by the horizontal component of the liquid bridge force. After standing until the solvent has fully reacted, the chip cover plate and the chip substrate are tightly bonded together, and the bonding is completed. The microfluidic chip is heated until the phase change material in the microfluidic channel melts, and then the molten phase change material in the microfluidic channel is blown out through the first and second through holes, thus completing the encapsulation of the microfluidic chip.

2. The PMMA microfluidic chip packaging method as described in claim 1, characterized in that, The phase change material is any one of sodium thiosulfate, agar, paraffin, and polycaprolactone.

3. The PMMA microfluidic chip packaging method as described in claim 1, characterized in that, The solvent is selected from any one of toluene, dichloromethane, acetic acid, dichloroethane, methane cyanide, acetone, and isopropanol.

4. The PMMA microfluidic chip packaging method as described in claim 1, characterized in that, The thickness of the solvent covering the bonding surface of the chip substrate is 100-200 μm.

5. The PMMA microfluidic chip packaging method as described in claim 1, characterized in that, The melting point of the phase change material is in the range of 30-100℃.

6. The PMMA microfluidic chip packaging method as described in claim 1, characterized in that, The heating temperature is greater than the melting point of the phase change material but less than 115 degrees Celsius.

7. The PMMA microfluidic chip packaging method as described in claim 1, characterized in that, Also includes: After the molten phase change material completely fills the microfluidic channel, the excess phase change material on the chip substrate is scraped off.

8. The PMMA microfluidic chip packaging method as described in claim 1, characterized in that, Also includes: After blowing out the molten phase change material from the microfluidic channel, the microfluidic channel is cleaned and dried.

9. The PMMA microfluidic chip packaging method according to any one of claims 1 to 8, characterized in that, Also includes: During the bonding process, bonding efficiency can be improved by at least one of the following methods: increasing ambient temperature, microwave treatment, and ultraviolet light treatment.

10. A PMMA microfluidic chip, characterized in that, It is packaged using the method described in any one of claims 1 to 9.

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