Micro-fluidic chip and method for high-flux large-scale preparation of liquid drops

Abstract

The invention belongs to the technical field of microfluidics, and particularly relates to a microfluidic chip and a method for preparing liquid drops in a high-flux and large-scale manner. A step emulsification structure and a liquid drop splitting structure are used together, a liquid drop generation structure is arranged at the communication position of a branch splitting channel and a main channel unit correspondingly communicated with the branch splitting channel, a dispersion phase necks at the liquid drop generation structure under the action of interfacial tension to form liquid drops, and the liquid drops are generated under the leading of the interfacial tension, so that the dispersion phase is uniform in dispersion. Therefore, the size of the liquid drops is basically determined by the channel width of the liquid drop generation structure, the branch splitting channel is designed to be wide, the influence of manufacturing errors on the uniformity of the generated liquid drops can be reduced, the branch splitting channel is designed to be a plurality of serpentine channels, and the uniformity of the liquid drops is improved while high-flux liquid drop preparation is guaranteed; and then the liquid drops flow through the main channel unit and are converged into the main splitting channel, and the liquid drops are uniformly split into liquid drops with smaller sizes through the liquid drop splitting structure, so that the preparation of the liquid drops with high flux and uniform sizes is realized.

Description

Technical Field

[0001] This invention belongs to the field of microfluidics technology, specifically relating to a microfluidic chip and method for high-throughput, large-scale preparation of droplets. Background Technology

[0002] Microfluidics refers to a class of technologies that precisely manipulate fluids in channels at the micrometer scale, and it has important applications in various industries such as food processing, cosmetics production, and biomedical testing. As a branch of this technology, droplet microfluidics focuses on generating well-dispersed droplets in multiphase fluid systems. These droplets are typically used as precursors, and after solidification, they can be used to produce microspheres with uniform particle size and controllable dimensions. However, because traditional microfluidic chips can only generate a limited number of droplets per unit time, their processing capacity is often insufficient to meet the requirements of industrial-grade production.

[0003] To improve the throughput of microfluidic chips, existing technologies generally achieve channel integration by increasing the number of channels. Parallel integration of channels is a commonly used improvement strategy. Parallel integration refers to arranging multiple droplet generation channels in parallel along one dimension. This integration method is simple; it only requires expanding the number of channels on that plane according to actual needs. Interfacial tension forming droplets is a common droplet preparation method in microfluidic systems, generally taking the form of stepped emulsification. The size of the prepared droplets is basically determined by the channel width. Especially for the preparation of smaller droplets, setting a large number of channels poses a challenge to the precision of the processing technology. Processing errors can easily exist between multiple channels, leading to reduced droplet uniformity. Therefore, how to achieve high-throughput droplet preparation while ensuring droplet uniformity is a problem that needs to be overcome. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention provides a microfluidic chip for high-throughput, large-scale droplet fabrication. The microfluidic chip designed in this invention combines a stepped emulsification structure and a droplet splitting structure. First, a wider stepped emulsification structure is used to fabricate large-diameter droplets, reducing the impact of channel width errors during precision manufacturing on droplet uniformity. Then, the large-diameter droplets are split into smaller droplets. The number of droplet splitting operations can be designed according to requirements, enabling high-throughput fabrication of droplets of different sizes.

[0005] The present invention is specifically implemented through the following technical solutions.

[0006] A microfluidic chip for high-throughput, large-scale preparation of droplets includes a continuous phase channel unit and a dispersed phase channel unit.

[0007] The continuous phase channel unit includes two main channel units, which are arranged in a U-shape. The two main channel units have the same outlet. At the outlet of the two main channel units, they split to form a main split channel structure with a tree structure (the number of channels obtained by splitting can be adjusted according to actual needs). Each splitting point of the tree structure is a droplet splitting structure. The outlet of the main split channel structure is connected to the amplification section structure, and the outlet of the amplification section structure is connected to a collection port.

[0008] The dispersed phase channel unit includes a branch channel unit located inside the loop structure. Multiple branch splitting channels are symmetrically connected along the length of the branch channel unit. The outlet of each branch splitting channel is connected to the main channel unit at the corresponding position. The connection between the branch splitting channel and the main channel unit is a droplet generation structure. The dispersed phase comes into contact with the continuous phase in the main channel unit through the branch splitting channel and generates droplets in the droplet generation structure. The droplets flow into the main splitting channel structure and are uniformly split into smaller droplets by the droplet splitting structure, which then enter the amplification section structure and the collection port.

[0009] The inner diameter of the branch channel is equal to the outlet inner diameter of the two main channel units, and larger than the inner diameter of any one of the main channel structures. Since droplets are generated primarily by interfacial tension, the size of the droplets is mainly determined by the width of the channel. The branch channel is designed to be relatively wide, so manufacturing errors have a smaller impact on the uniformity of the droplets.

[0010] Preferably, the width of each branch channel is 190μm~210μm, more preferably 200μm.

[0011] Preferably, each branch channel has a serpentine structure and the length of each branch channel is equal. The serpentine dispersed phase channel can effectively increase the proportion of active microchannels and improve the uniformity of droplets.

[0012] Preferably, the droplet generation structure is a nozzle structure to prevent channel blockage from affecting droplet generation.

[0013] Preferably, each droplet splitting structure is used to uniformly split the droplet, and the multiple droplet splitting structures are symmetrically distributed.

[0014] Preferably, the main splitting channel structure includes multiple levels of main splitting channels, each level of main splitting channel is formed by splitting from the previous level, and the number of splits at each splitting site is 2.

[0015] Preferably, the two main channel units have the same continuous phase fluid inlet, and the two main channel units are symmetrically distributed with respect to the axis of the continuous phase fluid inlet, and the outlets of the two main channel units are located on the axis of the continuous phase fluid inlet.

[0016] Preferably, the outlets of the two main channel units are located inside the loop structure.

[0017] Preferably, the branch channel unit is provided with an inlet for the dispersed phase fluid.

[0018] The microfluidic chips for high-throughput, large-scale droplet fabrication mentioned above can be fabricated using soft photolithography, or by precision engraving, 3D printing, and other technologies.

[0019] This invention also provides a method for high-throughput, large-scale preparation of droplets, using the aforementioned microfluidic chip, comprising the following steps: The continuous phase solution is injected into two main channel units, while the dispersed phase solution is injected into the branch channel units. The dispersed phase solution is evenly distributed to all branch splitting channels through the branch channel units. The dispersed phase comes into contact with the continuous phase in the main channel units through the branch splitting channels. Under the action of interfacial tension, the dispersed phase forms droplets in the droplet generation structure. Then, the droplets flow through the main channel units and merge into the main splitting channel structure. The droplet splitting structure splits the droplets into smaller droplets, which finally enter the collection port corresponding to the enlarged section structure. After the droplets are collected at the collection port, the continuous phase and the dispersed phase undergo a cross-linking reaction, thereby solidifying the droplets to form microspheres.

[0020] Compared with the prior art, the present invention has the following beneficial effects: This invention relates to a microfluidic chip for high-throughput, large-scale droplet fabrication, comprising a continuous phase channel unit and a dispersed phase channel unit. The continuous phase channel unit includes two main channel units forming a U-shaped structure with a common outlet. At the outlet of each main channel unit, the main channel unit splits into a tree-like main splitting channel structure. Each splitting point of the tree structure represents a droplet splitting structure. The outlets of the main splitting channel structures are connected to an amplification section structure, which in turn connects to a collection port. The dispersed phase channel unit includes a branch channel unit located inside the U-shaped structure. Along the length of the branch channel unit, multiple branch splitting channels are symmetrically connected. The outlet of each branch splitting channel is connected to a corresponding main channel unit, and the connection point between the branch splitting channel and the main channel unit forms a droplet generation channel. The dispersed phase contacts the continuous phase in the main channel unit through the branch splitting channel, generating droplets in the droplet generation structure. These droplets flow into the main splitting channel structure, where they are split into smaller droplets that enter the amplification section structure and the collection port. This invention combines a stepped emulsification structure and a droplet splitting structure. First, a large-diameter droplet is prepared using a wider stepped emulsification structure, avoiding the influence of channel width errors on droplet uniformity during the precision manufacturing of small droplets. Then, the large-diameter droplet is split into smaller droplets. During this process, the size error of the droplet splitting is small, which can ensure the monodispersity of the final small droplets.

[0021] Compared to existing technologies that directly form small droplets of the final size from the dispersed phase within a continuous phase, this invention first employs larger-sized branch channel units to transport the dispersed phase. Under the influence of interfacial tension, the dispersed phase forms larger droplets at the droplet generation structure. Since droplet generation is primarily driven by interfacial tension, the droplet size is largely determined by the channel width. The branch splitting channel design is relatively wide, thus minimizing the impact of manufacturing errors on droplet uniformity. Furthermore, the serpentine dispersed phase channel effectively increases the proportion of active microchannels, improving droplet uniformity. Subsequently, the droplets flow through the main channel unit and merge into the main splitting channel, where the droplet splitting structure further divides the droplets into smaller droplets. The designed droplet splitting structure tree network is symmetrical in structure, with consistent flow resistance into the main splitting channel, ensuring symmetrical splitting and guaranteeing uniform droplet splitting. This enables high-throughput, large-scale preparation of uniformly sized droplets. In addition, droplet splitting is also applied to the integrated amplification of microfluidic units, but in existing technologies, only one droplet generation structure is usually connected, resulting in relatively low throughput. This invention combines high-throughput stepped emulsification for droplet preparation with droplet splitting technology to further improve the throughput of droplet preparation.

[0022] The present invention has two main channel units enclosed in a loop-shaped structure, and a dispersed phase transport mechanism is set within the loop-shaped structure, making full use of space. The structure is compact and reasonable, which is conducive to the integration of droplet preparation. Attached Figure Description

[0023] Figure 1 A schematic diagram of the microfluidic chip structure for high-throughput, large-scale droplet preparation provided by this invention.

[0024] Explanation of reference numerals in the attached figures: 1-1: Main channel unit; 1-2: Main splitting channel structure; 1-3: Main splitting channel; 2-1: Branch channel unit; 2-2: Branch splitting channel; 3-1: Droplet generation structure; 3-2: Droplet splitting structure; 4: Continuous phase fluid inlet; 5: Dispersed phase fluid inlet; 6: Collection port; 7: Magnification section structure. Detailed Implementation

[0025] To enable those skilled in the art to better understand and implement the technical solutions of the present invention, the present invention will be further described below with reference to specific embodiments and accompanying drawings. However, the embodiments described are not intended to limit the present invention. Unless otherwise specified, the experimental methods and detection methods described in the following embodiments are conventional methods; unless otherwise specified, the reagents and materials described are commercially available.

[0026] In existing technologies, the size of droplets prepared by stepped emulsion structures is primarily determined by the channel width. This is particularly problematic for smaller droplets, where a large number of channels poses a challenge to the precision of the manufacturing process. Manufacturing errors can easily arise between multiple channels, leading to reduced droplet uniformity. Furthermore, the proportion of active channels decreases with increasing channel count, thus reducing the efficiency of microsphere preparation. To address this issue, this invention modifies the droplet preparation strategy. First, a wider stepped emulsion structure is used to prepare large-diameter droplets, reducing the impact of channel width errors during precision manufacturing on droplet uniformity. Then, the large-diameter droplets are split into smaller droplets. The number of splitting operations can be designed according to requirements, enabling high-throughput preparation of droplets of different sizes. This invention designs a wider dispersed phase channel, minimizing the impact of manufacturing errors on droplet uniformity. The subsequent use of a droplet splitting structure allows for high-throughput preparation of uniform droplets smaller than 100 micrometers with only two or three splitting operations. For even smaller droplets, simply increase the number of splitting channels.

[0027] The invention will now be described in detail.

[0028] like Figure 1 As shown, the present invention provides a microfluidic chip for high-throughput large-scale preparation of droplets, including a substrate, wherein a continuous phase channel unit and a dispersed phase channel unit are provided on the substrate; wherein the continuous phase channel unit is used to transport a continuous phase solution and the dispersed phase channel unit is used to transport a dispersed phase solution.

[0029] The continuous phase channel unit includes two main channel units 1-1, which together form a loop-shaped structure. The two main channel units 1-1 have the same outlet. At the outlet of the two main channel units 1-1, they split to form a main split channel structure 1-2 with a tree-like structure. Each split point of the tree-like structure is a droplet splitting structure 3-2. The outlet of the main split channel structure 1-2 is connected to the amplification section structure 7. The outlet of the amplification section structure 7 is connected to a collection port 6.

[0030] It should be noted that the main splitting channel structure 1-2 of the tree structure is symmetrical. The channels that split out each time are symmetrical, that is, the length, angle, etc. are the same, and each time they split into 2 branches, so that the droplet can split uniformly and improve the monodispersity of the droplet.

[0031] The dispersed phase channel unit includes a branch channel unit 2-1 located inside the loop structure. Multiple branch split channels 2-2 are symmetrically connected along the length of the branch channel unit 2-1. The outlet of each branch split channel 2-2 is connected to the main channel unit 1-1 at the corresponding position. The connection between the branch split channel 2-2 and the main channel unit 1-1 is the droplet generation structure 3-1. The dispersed phase comes into contact with the continuous phase in the main channel unit 1-1 through the branch split channel 2-2 and generates droplets at the droplet generation structure 3-1. The droplets flow into the main split channel structure 1-2 and are uniformly split into smaller droplets by the droplet split structure 3-2, which then enter the amplification section structure 7 and the collection port 6.

[0032] It should be noted that the continuous phase solution and the dispersed phase solution come into contact with the corresponding main channel unit 1-1 through a branch-splitting channel 2-2. Under the action of interfacial tension, the dispersed phase forms droplets in the droplet-forming structure 3-1. The inner diameter of the branch-splitting channel 2-2 is equal to the outlet inner diameter of the two main channel units 1-1, and larger than the inner diameter of any one of the channels in the main splitting channel structure 1-2. The generated large-diameter droplets enter the outlet of the two main channel units 1-1, and then split into smaller-diameter droplets sequentially. The aforementioned limitation on the inner diameter ensures that a droplet splits uniformly at the outlet of the two main channel units 1-1.

[0033] In a preferred embodiment of the present invention, the inner diameter of the branch-splitting channel 2-2 is 190μm~210μm, preferably 200μm. With this inner diameter width, the influence of manufacturing errors on the uniformity of the droplets can be reduced. The branch-splitting channel 2-2 has a serpentine structure, and the length of each branch-splitting channel 2-2 is equal, which can effectively increase the proportion of active microchannels and improve the uniformity of the droplets.

[0034] To ensure the uniformity of droplet generation, the droplet generation structure 3-1 is specifically a nozzle structure to prevent channel blockage from affecting droplet generation.

[0035] Multiple droplet splitting structures 3-2 are symmetrically distributed, presenting a tree-like network structure. Their symmetrical structure and consistent flow resistance into the main splitting channel structure 1-2 ensure symmetrical splitting, guaranteeing uniform droplet splitting and enabling high-throughput, scalable preparation of uniformly sized droplets. The main splitting channel structure 1-2 comprises multiple levels of main splitting channels 1-3, each level formed by the splitting of the previous level, with two splitting points at each splitting site. The number of splitting levels can be set according to actual needs. Droplets smaller than 100 micrometers can be prepared with only two or three splits; to prepare even smaller droplets, additional splitting channels can be added.

[0036] The two main channel units 1-1 share a common continuous phase fluid inlet 4, and are symmetrically distributed with respect to the axis of the continuous phase fluid inlet 4. The outlets of the two main channel units 1-1 are located on the axis of the continuous phase fluid inlet 4. The continuous phase is injected into the two main channel units 1-1 through the continuous phase fluid inlet 4. To ensure the same flow rate in both main channel units 1-1, the continuous phase fluid inlet 4 is located at the center of symmetry. Furthermore, to ensure that the droplets from both main channel units 1-1 flow out simultaneously, the outlets are located on the axis of the continuous phase fluid inlet 4; that is, both the inlet and outlet are on the axis of symmetry. The outlets of the two main channel units 1-1 are located inside the loop-shaped structure to fully utilize space, improve structural compactness, and facilitate the integration of droplet preparation.

[0037] Branch channel unit 2-1 is provided with an inlet 5 for the dispersed phase fluid, through which the dispersed phase is injected into branch channel unit 2-1.

[0038] The high-throughput, scalable droplet microfluidic chip provided by this invention is simple to manufacture, requiring only soft photolithography, and can also be fabricated using precision engraving, 3D printing, and other technologies. It is easily mass-produced. This invention first employs a large-sized branched channel to transport the dispersed phase. Under the influence of interfacial tension, the dispersed phase forms large droplets at the droplet generation structure. Since droplet generation is primarily driven by interfacial tension, the droplet size is largely determined by the channel width. The wide branched channel design minimizes the impact of manufacturing errors on droplet uniformity. Furthermore, the serpentine dispersed phase channel effectively increases the proportion of active microchannels, improving droplet uniformity. The droplets then flow through the main channel unit into the main splitting channel, where the droplet splitting structure further divides the droplets into smaller droplets. The designed droplet splitting structure tree network is symmetrical, with consistent flow resistance into the main splitting channel, ensuring symmetrical splitting and guaranteeing uniform droplet splitting. This enables high-throughput, scalable, and uniformly sized droplet production. The present invention has two main channel units enclosed in a loop-shaped structure, and a dispersed phase transport mechanism is set within the loop-shaped structure, making full use of space. The structure is compact and reasonable, which is conducive to the integration of droplet preparation.

[0039] This invention provides a method for high-throughput, large-scale preparation of droplets, using the aforementioned microfluidic chip, comprising the following steps: The continuous phase solution is injected into the main channel unit 1-1, while the dispersed phase solution is injected into the branch channel unit 2-1. The dispersed phase solution is distributed to all branch splitting channels 2-2 through the branch channel unit 2-1. The continuous phase solution and the dispersed phase solution come into contact with the corresponding main channel unit 1-1 through a branch splitting channel 2-2. Under the action of interfacial tension, the dispersed phase necks in the droplet generation structure 3-1 to form droplets. Then, the droplets flow through the main channel unit 1-1 and merge into the main splitting channel 1-2. The droplet splitting structure 3-2 splits the droplets into smaller droplets, which finally enter the collection port 6 connected to the amplified section structure 7. After the droplets are collected in the collection port 6, the continuous phase and the dispersed phase undergo a cross-linking reaction, thereby solidifying the droplets to form microspheres.

[0040] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, it is intended to include any modifications and variations that fall within the scope of the claims and their equivalents.

Claims

1. A microfluidic chip for high-throughput scale-up production of droplets, characterized in that, Includes continuous phase channel units and dispersed phase channel units; The continuous phase channel unit includes two main channel units (1-1), which are arranged in a loop shape. The two main channel units (1-1) have the same outlet. At the outlet of the two main channel units (1-1), they split to form a main split channel structure (1-2) with a tree structure. Each split point of the tree structure is a droplet split structure (3-2). The outlet of the main split channel structure (1-2) is connected to the amplification section structure (7), and the outlet of the amplification section structure (7) is connected to a collection port (6). The dispersed phase channel unit includes a branch channel unit (2-1), which is located inside the loop structure. Multiple branch split channels (2-2) are symmetrically connected along the length of the branch channel unit (2-1). The outlet of each branch split channel (2-2) is connected to the corresponding main channel unit (1-1). The connection between the branch split channel (2-2) and the main channel unit (1-1) is a droplet generation structure (3-1). The inner diameter of the branch split channel (2-2) is equal to the outlet inner diameter of the two main channel units (1-1) and is larger than the inner diameter of any channel in the main split channel structure (1-2). The dispersed phase comes into contact with the continuous phase in the main channel unit (1-1) through the branch splitting channel (2-2) and generates droplets in the droplet generation structure (3-1). The droplets flow into the main splitting channel structure (1-2) and are uniformly split by the droplet splitting structure (3-2). The split droplets enter the amplification section structure (7) and the collection port (6).

2. The microfluidic chip for high-throughput scale-up production of droplets according to claim 1, wherein, The inner diameter of each branch channel (2-2) is 190μm~210μm.

3. The microfluidic chip for high-throughput scale-up production of droplets according to claim 1, wherein, Each branch channel (2-2) has a serpentine structure, and the length of each branch channel (2-2) is equal.

4. The microfluidic chip for high-throughput scale-up production of droplets according to claim 1, wherein, The droplet generation structure (3-1) is a nozzle structure.

5. The microfluidic chip for high-throughput scale-up production of droplets according to claim 1, wherein, Each droplet splitting structure (3-2) is used to uniformly split a single droplet, and multiple droplet splitting structures (3-2) are distributed symmetrically among them.

6. The microfluidic chip for high-throughput scale-up production of droplets according to claim 1, wherein, The main splitting channel structure (1-2) includes multiple main splitting channels (1-3), each main splitting channel (1-3) is formed by splitting from the previous level, and the number of splits at each splitting site is 2.

7. The microfluidic chip for high-throughput scale-up production of droplets according to claim 1, wherein, The two main channel units (1-1) have the same continuous phase fluid inlet (4), and the two main channel units (1-1) are symmetrically distributed with respect to the axis of the continuous phase fluid inlet (4). The outlets of the two main channel units (1-1) are located on the axis of the continuous phase fluid inlet (4).

8. The microfluidic chip for high-throughput scale-up production of droplets according to claim 7, wherein, The outlets of the two main channel units (1-1) are located inside the loop structure.

9. The microfluidic chip for high-throughput scale-up production of droplets according to claim 1, wherein, The branch channel unit (2-1) is provided with an inlet (5) for the dispersed phase fluid.

10. A method of high-throughput scale-up of droplet production, characterized in that, The fabrication of the microfluidic chip according to claim 1 includes the following steps: The continuous phase solution is injected into two main channel units (1-1), and the dispersed phase solution is injected into the branch channel unit (2-1), and the dispersed phase solution is uniformly distributed to all branch split channels (2-2) through the branch channel unit (2-1), and the dispersed phase contacts the continuous phase in the main channel unit (1-1) through the branch split channel (2-2), and under the action of interfacial tension, the dispersed phase forms droplets in the droplet generation structure (3-1); Then the droplets flow through the main channel unit (1-1) and enter the main split channel structure (1-2), and the droplets are uniformly split through the droplet split structure (3-2), and the split droplets enter the corresponding collection port (6) of the amplification section structure (7); after the droplets are collected in the collection port (6), the continuous phase and the dispersed phase cross-link to form microspheres.

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