Double-emulsification high-flux micro-fluidic chip

Abstract

The utility model provides a double-emulsification high-flux micro-fluidic chip. The double-emulsification high-flux micro-fluidic chip comprises a substrate, a middle layer and a cover plate, according to the utility model, the substrate is not processed, the main micro-channels are processed on the two sides of the middle layer, and the cover plate is punched, so that fluid can be conveniently introduced. A plurality of liquid drop generation units based on the flow focusing technology are designed on one side of the middle layer so as to generate liquid drops for the first time, and a stepped liquid drop generation structure based on interfacial tension is designed on the other side of the middle layer so as to generate liquid drops for the second time. The structures on the two sides of the chip are connected through the through holes. The preparation method comprises the following steps: carrying out photoetching to form a mold, preparing the middle layer by using the mold, forming the required micro-channels on the two sides of the middle layer, punching on the cover plate, and finally bonding the substrate, the middle layer and the cover plate. Through the design of the flow channel and the structure, a large number of double-emulsion droplets can be rapidly prepared, the production efficiency is improved, and the double-emulsion droplet preparation device is suitable for various applications such as drug delivery and biological research.

Description

Technical Field

[0001] The utility model relates to the technical field of microfluidics, and particularly relates to a double-emulsion high-throughput microfluidic chip. Background Technique

[0002] Double-emulsion technology, also known as multiple-emulsion technology, is a technology for forming another emulsion within an emulsion. This technology is widely used in fields such as food, medicine, cosmetics, and materials science. Its core lies in forming complex emulsion systems, such as water-in-oil-in-water (w / o / w) and oil-in-water-in-oil (o / w / o). The double-emulsion system is achieved through two emulsification steps. In the first emulsification, primary droplets are generated, and in the second emulsification, these primary droplets are encapsulated in secondary droplets, thereby forming an emulsion with a multiple structure.

[0003] Traditional double-emulsion methods mainly rely on high-speed stirring and phase inversion technology. The high-speed stirring method uses high-shear force equipment, such as a homogenizer or an ultrasonic processor, to mix two immiscible liquids and form an emulsion. The phase inversion method is to change the temperature or composition of the system to cause a phase transition in the originally stable emulsion, thereby forming a multiple emulsion. However, these methods often have difficulty in precisely controlling the droplet size and distribution, and the production efficiency is low. In addition, the high-intensity mechanical action may damage some sensitive substances, such as proteins or certain drug molecules.

[0004] In recent years, the rapid development of microfluidic technology has brought new opportunities to double-emulsion technology. Microfluidic technology is a technology for manipulating and processing fluids at the micron scale. It can achieve precise droplet generation and high-throughput production by designing precise flow channel structures and controlling fluid flow rates. In the development process of microfluidic technology, double-emulsion technology has shown great potential in applications such as droplet generation, drug delivery, and cell encapsulation. For example, in drug delivery, microfluidic double-emulsion technology can prepare multi-layer microcapsules with precise sizes and narrow distributions, and these microcapsules can effectively encapsulate water-soluble and oil-soluble drugs. In the field of cell research, microfluidic double-emulsion technology can be used to prepare artificial cells or tissues, providing new tools for tissue engineering and regenerative medicine. Content of the Utility Model

[0005] The purpose of the utility model is to provide a double-emulsion high-throughput microfluidic chip to solve the problems of stability and long-term stability, low production efficiency, and high cost existing in the prior art.

[0006] To solve the above technical problems, a double-emulsion high-throughput microfluidic chip provided by the utility model includes: a substrate, an intermediate layer, and a cover plate;

[0007] The intermediate layer is installed between the substrate and the cover plate, and the intermediate layer is provided with microchannels for droplet generation and transportation;

[0008] On one side of the middle layer, a plurality of droplet generation units based on flow focusing technology are provided to achieve the generation of the first droplets.

[0009] On the other side of the middle layer, a stepped droplet generation structure based on interfacial tension is provided to achieve the generation of the second droplets and form double emulsified droplets. Among them, in order to reduce the influence of the droplets generated by the front stepped structure on the droplets generated by the rear stepped structure during the second droplet generation process, all the stepped structure channels are evenly divided into two parts, and two dispersed phase inlets and a double emulsified droplet outlet are provided. If too many dispersed phase inlets and double emulsified droplet outlets are set, more equipment for pumping liquid is required, increasing the operation difficulty, experimental complexity, and the possibility of errors.

[0010] Furthermore, the structures on both sides of the middle layer are connected through through-holes for the droplets to flow from one side to the other side for double emulsification treatment.

[0011] The diameter of the through-hole is slightly larger than the width of the flow channel to ensure that the droplets can pass through smoothly without breaking or merging, and at the same time, the diameter should be kept within two times the width of the flow channel to ensure that the droplets do not pass through in parallel.

[0012] Furthermore, a plurality of holes are provided on the cover plate for introducing different fluids to achieve the multi-functional application of the microfluidic chip.

[0013] The positions of these holes correspond to the positions where the liquid flows into the middle layer channels, and the hole diameter is larger than the width of the flow channel to ensure that the fluid can enter the microchannel evenly and does not affect the overall structural strength of the chip.

[0014] Furthermore, the substrate, the middle layer, and the cover plate are assembled through a bonding process to form a complete double emulsification high-throughput microfluidic chip.

[0015] The bonding process can be methods such as plasma activation bonding, thermal bonding, or UV light curing. The selected bonding method needs to ensure the tight bonding between the various parts of the chip without affecting the structure and function of the microchannel.

[0016] Furthermore, the substrate is not processed, and all the microchannels are processed on both sides of the middle layer to reduce the error during chip bonding.

[0017] This design method can simplify the manufacturing process, improve the consistency and reliability of the chip, and also facilitate subsequent quality control and mass production.

[0018] Furthermore, the middle layer adopts specific materials and processing techniques to ensure the stability and efficiency during the droplet generation process.

[0019] The specific material can be a material with good optical transparency, chemical stability, and biocompatibility, such as polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), or epoxy resin, etc.

[0020] The processing techniques can include soft lithography, micro molding, or 3D printing, etc. These techniques can precisely replicate the complex structure of the microfluidic channels.

[0021] Preferably, through the channel and structure design, the double-emulsion high-throughput microfluidic chip can rapidly and massively prepare double-emulsion droplets, such as o / w / o, w / o / w, etc., greatly improving the production efficiency.

[0022] The channel design utilizes capillary action, shear force, and interfacial tension, etc., to achieve stable droplet generation and control.

[0023] Preferably, the double-emulsion high-throughput microfluidic chip is applicable to various applications such as drug delivery and biological research.

[0024] In terms of drug delivery, the double-emulsion droplets can serve as drug carriers, improving the stability and bioavailability of drugs. In biological research, it can be used in fields such as single-cell analysis, protein crystallization, and enzymology research.

[0025] Based on the same above concept, a preparation method of a double-emulsion high-throughput microfluidic chip is also provided, including the following steps:

[0026] In the first step, lithography is carried out to form a mold. The lithography process includes steps such as mask design, photoresist coating, exposure, and development. It is necessary to precisely control the parameters of each step to ensure the accuracy of the mold. Two molds need to be prepared, corresponding to the channels on both sides of the middle layer respectively.

[0027] In the second step, the middle layer is prepared using the mold, and the required microfluidic channels are formed on both sides of the middle layer; in the preparation process, the two molds need to be aligned, placed in a suitable container, and then liquid PDMS is poured into the mold. After degassing and thermal curing, a middle layer with a microfluidic channel structure is obtained.

[0028] In the third step, holes are drilled on the cover plate to allow the fluid to flow in and out; the hole-drilling process can use methods such as laser cutting or mechanical drilling. It is necessary to control the position and size of the holes to ensure precise docking with the microfluidic channels.

[0029] In the fourth step, the substrate, the middle layer, and the cover plate are bonded to obtain the final double-emulsion high-throughput microfluidic chip. The bonding process needs to be carried out in a clean environment to avoid impurities such as dust affecting the performance of the chip.

[0030] Compared with the prior art, the utility model has the following beneficial effects: Through the design of the flow focusing structure for the first emulsification and the stepped structure for the second emulsification, the generation of most double emulsion droplets can be achieved; This double-sided design of the middle layer flow channel simplifies the production process and reduces the errors caused during chip bonding compared with the bonding of multi-layer flow channels; Through this structural design, the chip area is smaller, more flow channels can be integrated on the same area, the production efficiency is higher, the rapid and large-scale preparation of double emulsion droplets is realized, the production efficiency is greatly improved, and it is applicable to a variety of application fields.

[0031] In addition, the double-emulsion high-throughput microfluidic chip proposed by the utility model also has the following advantages: High degree of integration: The generation, processing and collection of double emulsion droplets are realized on one chip, reducing the sample transfer and operation steps and lowering the experimental error. Strong controllability: By adjusting the flow rate of the fluid and the geometric parameters of the flow channel, the size, monodispersity and composition of the generated droplets can be precisely controlled. Reagent saving: Compared with the traditional batch preparation method, the microfluidic technology can significantly reduce the consumption of reagents, which is especially suitable for the treatment of precious or expensive samples. High throughput: The parallel operation of multiple droplet generation units enables the chip to generate a large number of double emulsion droplets in a short time, meeting the requirements of high-throughput screening. Flexibility: By changing the types and proportions of the injected fluids, different types and compositions of double emulsion droplets can be conveniently prepared to adapt to diverse experimental needs. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 is a schematic three-dimensional structure diagram of the double-emulsion high-throughput microfluidic chip provided by the embodiment of the utility model;

[0033] Figure 2 is Figure 1 a top-down 45° exploded view of the double-emulsion high-throughput microfluidic chip shown in

[0034] Figure 3 is Figure 1 a bottom-up 45° exploded view of the double-emulsion high-throughput microfluidic chip shown in

[0035] Figure 4 is Figure 1 a front view of the middle layer of the double-emulsion high-throughput microfluidic chip shown in

[0036] Figure 5 is Figure 4 a partial enlarged view of the stepped droplet generation structure based on interfacial tension of the middle layer of the double-emulsion high-throughput microfluidic chip shown in

[0037] Figure 6 is Figure 1 a rear view of the middle layer of the double-emulsion high-throughput microfluidic chip shown in

[0038] Figure 7 is Figure 6 a partial enlarged view of the droplet generation unit structure based on the flow focusing technique in the middle layer of the double-emulsion high-throughput microfluidic chip shown;

[0039] Figure 8 is Figure 1 a side view of the middle layer of the double-emulsion high-throughput microfluidic chip shown;

[0040] Figure 9 is a schematic three-dimensional structure diagram of the flow channel of the double-emulsion high-throughput microfluidic chip provided by the embodiment of the present utility model;

[0041] Figure 10 is Figure 1 a preparation flow chart of mold one of the middle layer of the double-emulsion high-throughput microfluidic chip shown;

[0042] Figure 11 is Figure 1 a preparation flow chart of mold two of the middle layer of the double-emulsion high-throughput microfluidic chip shown;

[0043] Figure 12 is Figure 1 a preparation flow chart of the middle layer of the double-emulsion high-throughput microfluidic chip shown.

[0044] Reference numerals: 1 - cover plate; 101 - cover plate outlet one; 102 - cover plate inlet one; 103 - cover plate inlet two; 104 - cover plate inlet three; 105 - cover plate inlet four; 106 - cover plate outlet two; 2 - middle layer; 201 - middle layer outlet one; 202 - middle layer inlet one; 203 - middle layer inlet two; 204 - middle layer inlet three; 205 - middle layer inlet four; 206 - middle layer outlet two; 3 - substrate; 4 - stepped droplet generation structure based on interfacial tension; 401 - inlet for second droplet generation; 402 - dispersed phase flow channel for second droplet generation; 403 - flared structure; 404 - continuous phase flow channel for second droplet generation; 5 - droplet generation unit structure based on flow focusing technique; 501 - dispersed phase flow channel for first droplet generation; 502 - continuous phase flow channel for first droplet generation; 503 - flow focusing structure; 504 - outlet for first droplet generation; 6 - vertical connection flow channel; 7 - silicon wafer; 8 - photoresist; 9 - X-ray; 10 - mask plate one; 11 - copper; 12 - mask plate two; 13 - mold one; 14 - mask plate three; 15 - mask plate four; 16 - mold two; 17 - PDMS. Detailed implementation manners

[0045] Example 1

[0046] As Figure 1-9As shown in the figure, a double-emulsion high-throughput microfluidic chip provided in this embodiment includes: a cover plate 1, an intermediate layer 2, and a substrate 3; the intermediate layer 2 is installed between the substrate 3 and the cover plate 1, and the intermediate layer 2 is provided with microchannels for the generation and transportation of droplets.

[0047] On the basis of the above features, further preferably, a plurality of droplet generation units 5 based on the flow focusing technology are provided on one side of the intermediate layer 2 for realizing the generation of the first droplets; a stepped droplet generation structure 4 based on the interfacial tension is provided on the other side of the intermediate layer 2 for realizing the generation of the second droplets to form double-emulsion droplets.

[0048] Among them, the structures on both sides of the intermediate layer 2 are connected by a vertical connecting channel 6 for the droplets to flow from the first droplet generation outlet 504 to the second droplet generation inlet 401 for double-emulsion treatment; the diameter of the vertical connecting channel 6 is slightly larger than the width of the channel to ensure that the droplets can pass through smoothly without breaking or merging, and at the same time, the diameter should be kept within two channel widths to ensure that the droplets do not pass through in parallel.

[0049] More preferably, a plurality of holes are provided on the cover plate 1, including a cover plate outlet one 101, a cover plate inlet one 102, a cover plate inlet two 103, a cover plate inlet three 104, a cover plate inlet four 105, and a cover plate outlet two 106 for introducing and flowing out different fluids to realize the multifunctional application of the microfluidic chip. The positions of these holes correspond to the positions where the fluids flow into the intermediate layer channels, and the hole diameters are larger than the widths of the channels to ensure that the fluids can enter and leave the microchannels evenly and do not affect the overall structural strength of the chip.

[0050] Among them, the cover plate inlet one 102 introduces the dispersed-phase liquid for generating the first droplets, that is, the inner-phase liquid of the double-emulsion droplets; the cover plate inlet four 105 introduces the continuous-phase liquid for generating the first droplets, that is, the intermediate-phase liquid of the double-emulsion droplets, which is also called the isolation layer liquid; the cover plate inlet two 103 and the cover plate inlet three 104 introduce the continuous-phase liquid for generating the second droplets, that is, the outer-phase liquid of the double-emulsion droplets; the cover plate outlet one 101 and the cover plate outlet two 106 flow out the double-emulsion droplets. Among them, the functions of the cover plate inlet two 103 and the cover plate outlet one 101 can be interchanged, and the functions of the cover plate inlet three 104 and the cover plate outlet two 106 can be interchanged, and there are four usage methods according to the permutation and combination.

[0051] The droplet generation unit 5 based on flow focusing technology includes: a dispersed phase flow channel 501 for generating droplets for the first time, a continuous phase flow channel 502 for generating droplets for the first time, a flow focusing structure 503, and an outlet 504 for generating droplets for the first time. The step-by-step droplet generation structure 4 based on interfacial tension includes: an inlet 401 for generating droplets for the second time, a dispersed phase flow channel 402 for generating droplets for the second time, a bell-mouth structure 403, and a continuous phase flow channel 404 for generating droplets for the second time.

[0052] When the chip is in use, the dispersed phase and continuous phase liquids of the first generated droplets enter the middle layer inlet 1202 and the middle layer inlet 205 through the cover plate inlet 102 and the cover plate inlet 4 105 respectively, and then flow into the dispersed phase flow channel 501 and the continuous phase flow channel 502 of the first generated droplets, forming the first droplets at the flow focusing structure 503, and flow out from 504, enter the inlet 401 for the second generation of droplets through the vertical connecting flow channel 6, and then flow into the dispersed phase flow channel 402 for the second generation of droplets, and meet the continuous phase liquid flowing in from the continuous phase flow channel 404 of the second generation of droplets at the trumpet structure 403 to form the second droplets, realizing the double emulsification process.

[0053] Furthermore, the substrate 3, the intermediate layer 2 and the cover plate 1 are assembled by a specific bonding process to form a complete double-emulsification high-throughput microfluidic chip. The bonding process can be plasma activated bonding, thermal bonding or UV light curing, and the selected bonding method needs to ensure the close bonding between the various parts of the chip without affecting the structure and function of the microchannel.

[0054] It is worth noting that the substrate 3 is not processed, and all microchannels are processed on both sides of the middle layer 2 to reduce the error during chip bonding. This design method can simplify the manufacturing process, improve the consistency and reliability of the chip, and also facilitate subsequent quality control and mass production.

[0055] In this embodiment, the intermediate layer 2 is made of polydimethylsiloxane (PDMS) material and processed by soft lithography. PDMS has good optical transparency, chemical stability and biocompatibility, and is suitable for the manufacture of microfluidic chips. Soft lithography can accurately replicate the complex structure of the microchannel and ensure stability and efficiency during droplet generation.

[0056] The double emulsion high-throughput microfluidic chip of this embodiment can rapidly prepare double emulsion droplets, such as o / w / o, w / o / w, etc., through the flow channel and structural design, greatly improving the production efficiency. The flow channel design utilizes capillary phenomena, shear force, interfacial tension, etc. to achieve stable droplet generation and control.

[0057] In addition, the double-emulsion high-throughput microfluidic chip of this embodiment is applicable to various applications such as drug delivery and biological research. In terms of drug delivery, double-emulsion droplets can serve as drug carriers to improve the stability and bioavailability of drugs. In biological research, it can be used in fields such as single-cell analysis, protein crystallization, and enzymology research.

[0058] Example 2

[0059] This embodiment provides a preparation method for a double-emulsion high-throughput microfluidic chip, which mainly includes the preparation of a chip mold and the preparation of the chip.

[0060] The preparation steps of the chip mold are as follows:

[0061] Step 1: Clean the silicon wafer 7 with ethanol, deionized water, etc., and then dry it, as shown in Figure 10 a;

[0062] Step 2: Place the silicon wafer on a spin coater and coat photoresist 8. Since the thickness of the spin-coated photoresist is relatively large, spin coating can be carried out in multiple steps. After each spin coating, it is necessary to obtain Figure 10 b;

[0063] Step 3: Align the mask plate 10 with the silicon wafer 7 coated with photoresist 8, and use X-rays for exposure, as shown in Figure 10 c;

[0064] Step 4: Place the exposed silicon wafer 7 on a heating table for post-baking to further cure the photoresist;

[0065] Step 5: Immerse the silicon wafer 7 in the developer for development. The area irradiated by X-rays 9 undergoes a chemical reaction and is more easily dissolved in the developer. The developed pattern is as shown in Figure 10 d;

[0066] Step 6: Add copper 11 as a seed layer, as shown in Figure 10 e;

[0067] Step 7: Perform electroplating on the seed layer to fill the voids of the photoresist with copper 11 to form the required metal structure, as shown in Figure 10 f;

[0068] Step 8: After the electroplating in Step 7 is completed, spin coat an appropriate photoresist 8 and perform pre-baking to cure the photoresist, preparing for the processing of the second layer structure, as shown in Figure 10 g;

[0069] Step 9: Replace the mask plate 10 with the mask plate 2 12, and repeat Steps 3-7, as shown in Figure 10 h-k;

[0070] Step 10: Remove the redundant photoresist and seed layer, and finally obtain the first mold 13, as shown in Figure 10 Figure l.

[0071] The preparation steps of the second chip mold are similar to those of the first chip mold. It is necessary to use the third mask plate 14 and the fourth mask plate 15 to replace the first mask plate 10 and the second mask plate 12, and change the thickness of the photoresist according to the channel depth. The manufacturing steps are as shown in Figure 10 Figure, and finally obtain the second mold 16.

[0072] The preparation steps of the chip are as follows:

[0073] Step 1: Align the first mold 13 and the second mold 16, as shown in Figure 11 Figure a, and place them in a suitable container;

[0074] Step 2: Mix PDMS and curing agent in a ratio of 1:10. Pour the mixed PDMS 17 into the space between the two molds in multiple times. Each time PDMS 17 is poured, it needs to be placed in a vacuum drying oven to remove air bubbles;

[0075] Step 3: Place the mold filled with PDMS 17 and with air bubbles removed on a heating table and bake it at 80 °C for 3 - 4 hours to cure and form PDMS 17;

[0076] Step 4: Separate the first mold 13, the second mold 16 and the cured PDMS 17, as shown in Figure 11 Figure c;

[0077] Through the above steps, a double-emulsion high-throughput microfluidic chip can be prepared.

[0078] Example 3

[0079] This example provides a method for enzymatic research using the above double-emulsion high-throughput microfluidic chip, including the following steps:

[0080] (1) Prepare the enzyme and substrate solutions

[0081] Select appropriate enzymes and corresponding substrates, and prepare aqueous solutions with appropriate concentrations. For example, select β-galactosidase as the enzyme and fluorescein di-β-D-galactoside as the substrate, and prepare solutions of 1 mg / mL and 0.5 mM respectively. These solutions will be used as the inner aqueous phase.

[0082] (2) Prepare the oil phase

[0083] Select an oil phase with good biocompatibility, such as perfluoropolyether (HFE-7500). This oil phase will be used as the isolation layer.

[0084] (3) Prepare the outer aqueous phase

[0085] Prepare an aqueous solution containing a surfactant, such as a 0.5% (w / v) aqueous solution of polyoxyethylene (20) sorbitan monooleate (Tween 80). This will serve as the outer aqueous phase.

[0086] (4) Chip operation

[0087] Connect the prepared inner aqueous phase, oil phase, and outer aqueous phase to the corresponding inlets of the chip respectively. Adjust the flow rate ratios of each phase to be within a suitable range.

[0088] (5) Generation of double emulsion droplets

[0089] Start the injection pump. First, form w / o single emulsion droplets through the droplet generation unit based on flow focusing technology in the chip, and then enter the other side through the through-holes in the chip. Finally, form the w / o / w double emulsion droplets through the stepped droplet generation structure based on interfacial tension.

[0090] (6) Collection and observation

[0091] Collect the generated double emulsion droplets into a pre-prepared microplate. Observe the droplets using a fluorescence microscope and record the change in fluorescence intensity over time.

[0092] (7) Data analysis

[0093] By analyzing the change curve of fluorescence intensity over time, calculate the kinetic parameters of the enzyme, such as the Michaelis constant (Km) and the maximum reaction rate (Vmax). Compare the changes in kinetic parameters under different conditions (such as pH, temperature, in the presence of inhibitors), and deeply study the catalytic mechanism of the enzyme.

[0094] This method utilizes the advantages of a double emulsion high-throughput microfluidic chip to achieve enzyme research at the level of a single microreactor. Each double emulsion droplet can be regarded as an independent microreactor. The enzyme and substrate in the inner aqueous phase are isolated by the oil phase, avoiding mutual interference. At the same time, the outer aqueous phase facilitates the operation and detection of the droplets. This method has the advantages of less sample consumption, controllable reaction conditions, and high throughput, and can quickly and efficiently conduct enzyme research, providing a powerful tool for fields such as enzyme engineering and drug screening.

Claims

1. A double-emulsion high-throughput microfluidic chip, characterized in that: It includes a substrate, an intermediate layer and a cover plate. The intermediate layer is installed between the substrate and the cover plate. The intermediate layer is provided with microfluidic channels for the generation and transportation of droplets. On one side of the intermediate layer, there are multiple droplet generation units based on the flow focusing technology for realizing the generation of the first droplets. On the other side of the intermediate layer, there is a stepped droplet generation structure based on interfacial tension for realizing the generation of the second droplets to form double emulsion droplets. All the stepped structure channels are evenly divided into two parts, and two dispersed phase inlets and a double emulsion droplet outlet are provided. The structures on both sides of the intermediate layer are connected through through holes for the droplets to flow from one side to the other side for double emulsion treatment. The substrate is not processed, and all the microfluidic channels are processed on both sides of the intermediate layer.

2. The double-emulsion high-throughput microfluidic chip according to claim 1, characterized in that: The diameter of the through hole is slightly larger than the width of the channel, and at the same time, the diameter should be kept within two channel widths.

3. A double-emulsion high-throughput microfluidic chip according to claim 1, wherein: Multiple holes are provided on the cover plate for introducing different fluids to realize the multi-functional application of the microfluidic chip. The positions of these holes correspond to the positions where the liquid flows into the channels of the intermediate layer, and the hole diameter is larger than the width of the channel.

4. A double-emulsion high-throughput microfluidic chip according to claim 1, characterized in that: The substrate, the intermediate layer and the cover plate are assembled through a bonding process, and the bonding process is plasma activation bonding, thermal bonding or UV light curing.

5. A double-emulsion high-throughput microfluidic chip according to claim 1, characterized in that: The intermediate layer is made of polydimethylsiloxane, polymethyl methacrylate or epoxy resin materials. The processing technology includes soft lithography technology, micro molding or 3D printing.

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