Micro-fluidic chip micro-channel remodeling method based on PDMS swelling

Abstract

The invention relates to the field of micro-fluidic chip micro-channel modification and remodeling, in particular to a micro-fluidic chip micro-channel remodeling method based on PDMS swelling. Comprising a pressure pump which is connected with a liquid storage bottle through a gas pipeline and provides necessary power to drive fluid to flow. The liquid storage bottle is used for storing an organic solvent. And the flow controller is used for controlling the flow of the organic solvent in the liquid storage bottle through a fluid pipeline, so that the fluid is ensured to enter the micro-fluidic chip at a proper flow. The invention provides a micro-channel remodeling method for a micro-fluidic chip on the basis of the porous characteristic and the property that a PDMS material is easily permeated by an organic solvent, the organic solvent (such as hexadecane and tetradecane) is injected into a micro-channel, the organic solvent permeates a PDMS polymer network and causes PDMS to swell, and then the micro-channel of the micro-fluidic chip is remodeled, so that the micro-channel of the micro-fluidic chip is remodeled. Finally, the micro-fluidic chip with the special-shaped structure is constructed.

Description

Technical Field

[0001] The invention relates to the field of microfluidic chip microchannel modification and remodeling, in particular to a microfluidic chip microchannel remodeling method based on PDMS swelling. Background Art

[0002] Microfluidic chips are a technology that uses chips as operating platforms, analytical chemistry as a basis, micro-electromechanical processing technology, and micro-channel networks as structural features. They are mainly used in the field of life sciences. They manipulate fluids in micrometer-scale space, form networks through microchannels, and allow controllable fluids to run through the entire system, thereby realizing various functions of different laboratories such as conventional chemistry, biology, materials, and optics.

[0003] Existing microfluidic chip processing methods include excimer laser micromachining, femtosecond laser, stereolithography (SLA), fused deposition modeling (FDM), paper-based method, microwire molding method, embedded sacrificial component method, PDMS curing-glass bonding method, etc. Among them, PDMS curing-glass bonding method has been widely used due to its simple operation, high processing accuracy and low consumables cost. However, the microchannels of the microfluidic chips prepared by the above methods are fixed and difficult to deform and reshape.

[0004] In addition, a casting method for one-time molding of a macro-microstructure of a PDMS microfluidic chip is disclosed in publication number CN117984490A, which can quickly manufacture a PDMS microfluidic chip containing a microstructure and a macrostructure, accurately control the plane shape and thickness of the chip, and can mold and manufacture a high-precision, high-density through-hole structure in one time. However, for the microfluidic chip prepared by the invention, the geometric shape of its microchannel is fixed and unchanged, and it cannot be changed according to demand later. A method for making a PDMS microfluidic chip is disclosed in publication number CN117244599B, ​​which first uses paraffin to process a model including an outlet and an inlet of a microfluidic chip on a substrate, and then uses PMDS to mold on this model, so that PMDS is directly combined with the substrate, and then the paraffin model is removed, thereby obtaining a complete microfluidic chip, and there is no need to combine the upper cover with the base film again, and microfluidic chips of various shapes can be flexibly produced. However, for the microfluidic chip prepared by this invention, the geometric shape of its microchannel is also fixed, and the microchannel cannot be reshaped according to experimental requirements later. Summary of the invention

[0005] In view of the shortcomings of the prior art, the purpose of the present invention is to provide a method for reshaping microchannels of a microfluidic chip based on PDMS swelling. The present invention designs a method for reshaping microchannels of a microfluidic chip, wherein an organic solvent (such as hexadecane or tetradecane) is injected into the microchannel, and the organic solvent will penetrate the PDMS polymer network and cause the PDMS to swell, thereby reshaping the microchannels of the microfluidic chip, and finally constructing a microfluidic chip with a special-shaped structure.

[0006] In order to achieve the above object, the present invention is implemented through the following technical solutions:

[0007] First aspect The present invention provides a microfluidic chip microchannel swelling and deformation device, comprising:

[0008] The pressure pump provides the necessary power to drive the organic solvent into the microchannel of the microfluidic chip.

[0009] Liquid storage bottle, used to store organic solvents (such as hexadecane, tetradecane).

[0010] A flow controller is connected to the liquid storage bottle and the microfluidic chip, and is used to accurately control the flow of the fluid flowing into the microfluidic chip.

[0011] Microfluidic chips are used to induce microfluidic flow and conduct microfluidic experiments.

[0012] As a further implementation, the pressure pump is a vane pump, a positive displacement pump, or an electromagnetic pump.

[0013] As a further implementation, the liquid storage bottle is connected to the fluid inlet of the microfluidic chip.

[0014] As a further implementation, the flow controller can accurately control the flow of the fluid flowing into the microfluidic chip.

[0015] As a further implementation, the organic solvent is a reagent that can cause PDMS to swell, including but not limited to hexadecane and tetradecane.

[0016] Second aspect The present invention provides a method for reshaping a microchannel of a microfluidic chip based on PDMS swelling, using the microchannel swelling deformation device of the microfluidic chip as described in the first aspect, comprising the following steps:

[0017] Specifically, the pressure pump delivers high-pressure gas to the liquid storage bottle and squeezes the organic solvent into the fluid hose. Among them, the flow controller is responsible for adjusting the flow rate of the organic solvent to ensure that it reaches the microfluidic chip at an appropriate flow rate. The microfluidic chip has microchannels. Over time, the organic solvent in the microchannel gradually penetrates into the PDMS wall material, thereby inducing the swelling of PDMS. The cross-section of the microchannel is rectangular, which has a large aspect ratio. Therefore, the degree of swelling on the side is not high, while the top has more obvious swelling and sedimentation, realizing the reshaping of the microchannel structure.

[0018] As a further implementation method, after the organic solvent is injected into the microfluidic chip, the inlet of the microfluidic chip is sealed to ensure that the organic solvent fully penetrates the PDMS network.

[0019] As a further implementation, the pressure of the pressure pump is 0-100 kPa, and the flow rate adjustment range of the flow controller is 0-3000 μL / min.

[0020] The beneficial effects of the present invention are as follows:

[0021] Based on the porous characteristics of PDMS materials and their easy penetration by organic solvents, the present invention proposes a method for reshaping microchannels of microfluidic chips. When an organic solvent (such as hexadecane or tetradecane) is injected into the microchannel, the organic solvent will penetrate the PDMS polymer network and cause the PDMS to swell, thereby reshaping the microchannels of the microfluidic chip, and finally constructing a microfluidic chip with a special-shaped structure. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0023] Figure 1 It is a structural schematic diagram of the microchannel swelling and deformation device of the microfluidic chip in Example 1 of the present invention.

[0024] Figure 2 It is a schematic diagram, physical picture, and data analysis diagram of the microchannel of the microfluidic chip before and after swelling.

[0025] Figure 3 This is a schematic diagram of the reshaped microchannel, which shows three typical applications: rotating droplet mixer; high-throughput droplet digital PCR; and multiple-volume droplet 3D cell culture.

[0026] Figure 4 The first embodiment is adopted Figure 1The microfluidic chip constructed by the device is a rotating microdroplet mixer chip. A slight sedimentation occurs on the top of the microchannel, thereby constructing a non-uniform flow field and inducing microdroplet rotation. The chip is used for efficient mixing of two-phase fluids inside microdroplets.

[0027] Figure 5 The first embodiment is adopted Figure 1 The microfluidic chip constructed by the device is a high-throughput droplet digital PCR chip. A dramatic sedimentation occurs at the top of the microchannel and causes a partial blockage in the outlet area, thereby dividing the original outlet into two secondary outlets of equal size. Therefore, the structure can generate two droplets simultaneously, doubling the droplet generation rate. The chip is applied to high-throughput droplet digital PCR analysis.

[0028] Figure 6 The first embodiment is adopted Figure 1 The microfluidic chip constructed by the device is a multi-volume droplet 3D cell culture chip. A dramatic sedimentation occurs at the top of the microchannel and causes uneven blockage in the outlet area, thereby dividing the original outlet into two secondary outlets of unequal sizes. Therefore, the structure can simultaneously generate two droplets of different sizes to achieve multi-volume droplet generation. The chip is applied to droplet-type 3D cell culture.

[0029] In the figure: the distances or sizes between parts are exaggerated to show the positions of various parts, and the schematic diagram is for reference only.

[0030] Among them: 1. pressure pump; 2. gas pipeline; 3. liquid storage bottle; 4. organic solvent; 5. gas pipeline; 6. flow controller; 7. microfluidic chip; 8. microchannel. DETAILED DESCRIPTION

[0031] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0032] Embodiment 1

[0033] In a typical embodiment of the present invention, reference Figure 1 As shown, a microfluidic chip microchannel swelling and deformation device includes a pressure pump 1, a gas pipeline 2, a liquid storage bottle 3, an organic solvent 4, a fluid pipeline 5, a flow controller 6, and a microfluidic chip 7.

[0034] The pressure pump 1 is connected to the liquid storage bottle 3 through the gas pipeline 2 to provide the necessary power to drive the flow of the fluid. The pressure pump 1 is a vane pump or a volumetric pump or an electromagnetic pump to adapt to different fluid characteristics and pressure requirements.

[0035] The liquid storage bottle 3 is used to store the organic solvent 4. The flow controller 6 controls the flow of the organic solvent 4 in the liquid storage bottle 3 through the fluid pipeline 5 to ensure that the fluid enters the microfluidic chip 7 at a suitable flow rate.

[0036] The microfluidic chip 7 contains a microchannel 8, and the layout and size of the microchannel 8 are determined according to specific experimental requirements.

[0037] The gas pipeline 3 and the fluid pipeline 5 are made of glass, silicone or plastic.

[0038] In this embodiment, a pressure pump 1 is used to generate high-pressure gas, and the high-pressure gas is delivered to a liquid storage bottle 3 through a gas pipeline 2, thereby squeezing an organic solvent 4 into a fluid hose 5, and finally entering a microfluidic chip 7. Among them, a flow controller 6 is responsible for regulating the flow rate of the organic solvent 4 of the microfluidic chip 7, ensuring that a suitable volume of the organic solvent 4 is encapsulated in the microchannel 8. As time goes by, the organic solvent 4 gradually penetrates into the PDMS wall surface of the microchannel 8, causing the PDMS to swell, which is manifested as expansion and deformation of the microchannel in a macroscopic manner.

[0039] Based on the porous characteristics of PDMS materials and their easy penetration by organic solvents, the present invention proposes a method for reshaping microchannels of a microfluidic chip. An organic solvent 4 (such as hexadecane or tetradecane) is injected into a microchannel 8, and the organic solvent 4 will penetrate the PDMS polymer network and cause PDMS to swell, thereby reshaping the microchannel 8 of the microfluidic chip, and finally constructing a microfluidic chip 7 with a special-shaped structure.

[0040] The gas pressure in the pressure pump 1 is 0 to 100 kPa, and a variety of preset pressure options are provided, such as 20 kPa, 50 kPa, 70 kPa, 80 kPa or 100 kPa, but are not limited to the listed values. Other unlisted values ​​within the numerical range are also applicable to meet different fluid pumping requirements.

[0041] The pressure regulation range of the flow controller 6 is 0-100 kPa, such as 20 kPa, 40 kPa, 60 kPa, 80 kPa or 100 kPa, but is not limited to the listed values, and other values ​​not listed within the range are also applicable.

[0042] Using the device described in this embodiment, the top settlement deformation of the microchannel 8 is 2μm to 1000μm, such as 10μm, 50μm, 100μm or 800μm, but is not limited to the listed values. Other unlisted values ​​within the numerical range are also applicable.

[0043] The flow rate of the organic solvent 4 ranges from 10 μl / min to 3000 μl / min, including 20 μl / min, 300 μl / min, 1500 μl / min or 2000 μl / min, but is not limited to the listed values, and other unlisted values ​​within the numerical range are also applicable.

[0044] The cross-sectional shape design of the microchannel 8 included in the microfluidic chip 7 is not limited to circular, rectangular and other shapes, and the cross-sectional shape may include various shapes to meet the personalized microfluidic experiment requirements.

[0045] Figure 2 It is a schematic diagram and actual picture of the microfluidic chip microchannel before and after swelling.

[0046] Figure 3 This is a schematic diagram of the reshaped microchannel, which shows three typical applications: rotating droplet mixer, high-throughput droplet digital PCR, and multiple-volume droplet 3D cell culture.

[0047] Figure 4 It is a rotating droplet mixer chip. A slight sedimentation occurs at the top of the microchannel, which creates a non-uniform flow field and induces the rotation of the droplets. The chip is used for efficient mixing of two-phase fluids inside the droplets.

[0048] Figure 5 It is a high-throughput droplet digital PCR chip. The top of the microchannel has experienced a dramatic sedimentation and caused a partial blockage in the outlet area, thus dividing the original outlet into two secondary outlets of equal size. Therefore, the structure can generate two droplets simultaneously, doubling the droplet generation rate. The chip is used for high-throughput droplet digital PCR analysis.

[0049] Figure 6 It is a multi-volume droplet 3D cell culture chip. The top of the microchannel has experienced a dramatic sedimentation and caused uneven blockage in the outlet area, thus dividing the original outlet into two secondary outlets of unequal sizes. Therefore, the structure can simultaneously generate two droplets of different sizes, i.e., multi-volume droplet generation. The chip is used for droplet-based 3D cell culture.

[0050] Embodiment 2

[0051] This embodiment provides a method for reshaping a microchannel of a microfluidic chip based on PDMS swelling, using the microchannel swelling and deformation device described in Example 1, and specifically comprising the following steps:

[0052] (1) The pressure pump 1 compresses the external air and delivers it to the liquid storage bottle 3 through the gas pipeline 2.

[0053] (2) The controller 6 adjusts the fluid flow rate and delivers the organic solvent 4 at a suitable flow rate to the microfluidic chip 7 through the fluid hose 5 .

[0054] (3) The microfluidic chip 7 includes a microchannel 8, and the encapsulation time of the organic solvent in the microchannel 8 is 20 minutes. The organic solvent 4 gradually penetrates into the PDMS wall of the microchannel 8, causing the PDMS to swell, which is manifested as the expansion and deformation of the microchannel 8 in the macroscopic sense.

[0055] (4) After the above deformation, the microfluidic chip 7 is transformed into a rotating micro-mixer chip, which is used for efficient mixing of two-phase fluids inside microdroplets. Figure 4 As shown in a, the fluorescent hydrogel and the transparent hydrogel are respectively injected into the microchannel 8 from the two water phase inlets at the left end of the microfluidic chip 7. The two hydrogels are broken under the shearing action of the oil phase and form Janus droplets. Since the flow field in the microchannel is uneven, the Janus droplets rotate, thereby inducing efficient mass transfer between the two hydrogels and finally achieving efficient mixing. Figure 4 b shows the three-dimensional rotation behavior of the Janus droplet in the deformable microchannel 8. Figure 4 c shows the optical image of Janus droplet generation and rotation under dark field. Figure 4 d shows the variation of the mixing index, which increases with the increase of the droplet movement distance. Figure 4 e shows the normalized fluorescence intensity of the droplet, which reaches 0.92 after the droplet rotation is completed, indicating excellent mixing efficiency. Figure 4 f shows the rotation state of the droplets at different positions. It can be seen that when the movement distance reaches 10 mm, the rotation mixing has been completed.

[0056] Embodiment 3

[0057] This embodiment provides a microfluidic chip microchannel remodeling method based on PDMS swelling, which is different from the second embodiment in that the encapsulation time of the organic solvent in the microchannel 8 is greatly extended to 55 minutes. The organic solvent 4 gradually penetrates into the PDMS wall of the microchannel 8, causing the PDMS to swell more severely, which is manifested macroscopically as blockage at the outlet of the microchannel 8, thereby dividing the original outlet into two secondary outlets of equal size.

[0058] After the above deformation, the microfluidic chip 7 is transformed into a high-throughput droplet digital PCR chip, and is applied to high-throughput droplet digital PCR analysis. Figure 5As shown in FIG. 1 , the PCR sample containing the target gene is injected into the microchannel 8 from the water phase inlet at the left end of the microfluidic chip 7, and merged with the oil phase flowing in the vertical direction. Under the laminar flow principle, the two are transformed into sheath flow and flow in coordination in the microchannel 8. When the sheath flow reaches the outlet of the microchannel 8, it splits into two droplets of the same size, which is a multiplication droplet generation system. Figure 5 b shows the optical image of the droplet generation process. Figure 5 c shows the volume fraction of the internal phase fluid under different hydrodynamic modes of droplet generation. Figure 5 d shows the variation of the volume fraction of the inner phase fluid with the flow rate of the inner phase fluid. Figure 5 e shows the variation of droplet diameter with the flow rate of the internal phase fluid. Figure 5 f shows the stability of droplet size. Figure 5 g shows the fluorescence intensity comparison between positive and negative droplets. Figure 5 h shows the PCR experiment under different sample concentrations. As the sample concentration increases, the number of positive droplets increases, and the degree of match between the experimental value and the expected value is high.

[0059] Embodiment 4

[0060] This embodiment provides a method for reshaping microchannels of a microfluidic chip based on PDMS swelling. The difference from Embodiments 2 and 3 is that the encapsulation time of the organic solvent in the microchannel 8 is 55 minutes, and uneven blockage occurs at the outlet of the microchannel 8, thereby dividing the original outlet into two secondary outlets of unequal sizes.

[0061] After the above deformation, the microfluidic chip 7 is transformed into a multi-volume droplet 3D cell culture chip, which is applied to droplet 3D cell culture. Figure 6 As shown in FIG. 1 , the PCR sample containing the target gene is injected into the microchannel 8 from the water phase inlet at the left end of the microfluidic chip 7, and merged with the oil phase flowing in the vertical direction. Under the laminar flow principle, the two are transformed into sheath flow and flow in coordination in the microchannel 8. When the sheath flow reaches the outlet of the microchannel 8, it splits into two droplets of different sizes, that is, a multi-volume droplet generation system, thereby realizing multi-volume cell cluster 3D culture.

[0062] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A microfluidic chip microchannel swelling and deformation device, characterized in that: include: A pressure pump, which provides the necessary power to drive the organic solvent into the microchannel of the microfluidic chip; Liquid storage bottle, used to store organic solvents (such as hexadecane, tetradecane); A flow controller, connected to the liquid storage bottle and the microfluidic chip, for accurately controlling the flow of the fluid flowing into the microfluidic chip; Microfluidic chips are used to induce microfluidic flow and conduct microfluidic experiments.

2. A microfluidic chip microchannel swelling deformation device according to claim 1, characterized in that: The liquid storage bottle is connected to the fluid inlet of the microfluidic chip.

3. A microfluidic chip microchannel swelling and deformation device according to claim 1, characterized in that: The flow controller can accurately control the flow rate of the fluid flowing into the microfluidic chip.

4. The microfluidic chip microchannel swelling and deformation device according to claim 1, characterized in that: The organic solvent is a reagent that can cause PDMS to swell, including but not limited to hexadecane and tetradecane.

5. A method for reshaping a microchannel of a microfluidic chip based on PDMS swelling, obtained by using the microchannel swelling deformation device of a microfluidic chip according to any one of claims 1 to 4, characterized in that: The following steps are involved: The pressure pump delivers high-pressure gas to the liquid storage bottle and squeezes the organic solvent into the fluid hose, where the flow controller is responsible for adjusting the flow rate of the organic solvent to ensure that it reaches the microfluidic chip at an appropriate flow rate. The microfluidic chip has microchannels. Over time, the organic solvent in the microchannel gradually penetrates into the PDMS wall material, thereby inducing the swelling of PDMS; the cross-section of the microchannel is rectangular, which has a large aspect ratio, so the swelling degree of the side is not high, while the top has more obvious swelling and sedimentation, realizing the reshaping of the microchannel structure.

6. The method for reshaping microchannels of a microfluidic chip based on PDMS swelling according to claim 5, characterized in that: After the organic solvent is injected into the microfluidic chip, the inlet of the microfluidic chip is sealed to ensure that the organic solvent fully penetrates the PDMS network.

7. The method for reshaping microchannels of a microfluidic chip based on PDMS swelling according to claim 5, characterized in that: The pressure of the pressure pump is 0-100 kPa, and the flow rate adjustment range of the flow controller is 0-3000 μL / min.

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