Core-shell hydrogel microsphere preparation equipment

Abstract

The invention relates to core-shell hydrogel microsphere preparation equipment which comprises a microsphere preparation device and a microsphere collection device, the microsphere preparation device is provided with a nuclear phase inlet, a shell phase inlet, a plurality of nuclear phase distribution runners communicated with the nuclear phase inlet, and a plurality of shell phase distribution runners communicated with the shell phase inlet; the nuclear phase distribution flow channels and the shell phase distribution flow channels are converged into coaxial flow channels at the tail ends in a one-to-one correspondence manner; the microsphere collecting device comprises a microsphere collecting pool, the microsphere collecting pool is arranged below the coaxial flow channel, and the microsphere collecting pool is used for containing oil phase fluid; the nuclear phase fluid entering from the nuclear phase inlet and the shell phase fluid entering from the shell phase inlet form layered fluid at the coaxial flow channel, and the layered fluid is dropped into the microsphere collecting pool. According to the core-shell hydrogel microsphere preparation equipment provided by the invention, high-flux preparation of core-shell hydrogel microspheres can be realized.

Description

Technical Field

[0001] The present invention relates to the technical field of droplet microfluidics, in particular to a device for preparing core-shell hydrogel microspheres. Background Art

[0002] Droplet microfluidics technology has shown broad application prospects in the fields of materials science and biomedicine due to its advantages in the manipulation of droplets from microliters to femtoliters. However, traditional methods rely on complex microfluidic chip manufacturing processes and precise flow rate control, resulting in high production costs, poor stability and difficulty in scalability. Although the new microsphere generation technology based on wetting-induced interface destruction that has emerged in recent years has broken through the flow rate limitation and simplified the equipment structure, in the preparation of core-shell microspheres, the inconsistent flow rate ratios of multiple outlets lead to uneven shell thickness, which cannot meet the high-quality production requirements. In the existing technology, traditional microfluidics is limited by flow rate sensitivity and is difficult to achieve high-throughput production, while the new linear array technology cannot guarantee the uniformity of the core-shell structure. This dilemma seriously restricts the industrial application of core-shell hydrogel microspheres in the fields of drug delivery, cell therapy, etc., and there is an urgent need to develop a device that can achieve high-throughput preparation of core-shell hydrogel microspheres. Summary of the Invention

[0003] Based on this, the present application provides a core-shell hydrogel microsphere preparation device that can achieve high-throughput preparation of core-shell hydrogel microspheres.

[0004] A core-shell hydrogel microsphere preparation device, comprising: A microsphere preparation device is provided with a core phase inlet, a shell phase inlet, a plurality of core phase distribution flow channels connected to the core phase inlet, and a plurality of shell phase distribution flow channels connected to the shell phase inlet, wherein the core phase distribution flow channels and the shell phase distribution flow channels correspond to each other and merge into a coaxial flow channel at the end; A microsphere collecting device, comprising a microsphere collecting pool, the microsphere collecting pool being disposed below the coaxial flow channel and being used to place the oil phase fluid; The core phase fluid entering through the core phase inlet and the shell phase fluid entering through the shell phase inlet form a layered fluid at the coaxial flow channel and drip into the microsphere collection pool.

[0005] The core-shell hydrogel microsphere preparation equipment mentioned above has a core phase inlet and a shell phase inlet, which are used to inject the core material and coating material solutions, respectively. Each core phase flow channel corresponds to a shell phase flow channel, so that the core-shell fluid forms a stable coaxial flow when it converges at the end. Multiple flow channels work in parallel, and multiple core-shell microspheres can be generated at the same time, which greatly improves the output compared to single-channel microfluidic chips. At the same time, through precision processing and fluid control, the fluid behavior of all flow channels is ensured to be consistent, so that the core-shell structure of the entire batch of microspheres is highly uniform. The core phase distribution flow channel and the shell phase distribution flow channel can realize the distribution and encapsulation of the core-shell fluid. The microsphere collection device can receive and collect the formed core-shell microspheres. After the microspheres drip from the coaxial flow channel, they enter the collection pool filled with an oil phase medium (such as mineral oil, silicone oil, etc.). The microsphere collection device can ensure that the droplets can maintain a spherical shape when in contact with the oil phase and avoid damage to the core-shell structure.

[0006] In one embodiment, the coaxial flow channel includes a central core phase channel and an annular shell phase channel, the annular shell phase channel surrounds the outside of the central core phase channel, the central core phase channel is connected to the core phase distribution flow channel, and the annular shell phase channel is connected to the shell phase distribution flow channel.

[0007] In one embodiment, the coaxial flow channel includes an inner conical core phase outlet and an outer conical shell phase outlet, and the outer conical shell phase outlet is coaxially arranged with the inner conical core phase outlet; the end of the core phase distribution flow channel is connected to the inner conical core phase outlet, and the end of the shell phase distribution flow channel is connected to the outer conical shell phase outlet.

[0008] In one embodiment, the core phase distribution channel corresponds to the shell phase distribution channel in a one-to-one relationship in the height direction, the core phase distribution channel extends radially of the core phase inlet, and the shell phase distribution channel extends radially of the shell phase inlet.

[0009] In one embodiment, each of the core phase distribution flow channels is circumferentially periodically arranged relative to the core phase inlet, and each of the shell phase distribution flow channels is circumferentially periodically arranged relative to the shell phase inlet.

[0010] In one embodiment, the microsphere collection device includes an inner cavity, and the inner cavity is connected to the shell phase inlet.

[0011] In one embodiment, the microsphere collecting device includes a liquid level regulating chamber, and the top of the microsphere collecting pool is connected to the liquid level regulating chamber through a notch.

[0012] In one embodiment, the liquid level regulating chamber maintains the height of the solidified medium liquid level in the microsphere collection pool by adjusting the volume of the chamber.

[0013] In one embodiment, a light curing component is further included. The light curing component is arranged on the side of the microsphere collection device. At least a part of the microsphere collection device is a light-transmitting structure. The light curing component irradiates the microsphere collection pool through the light-transmitting structure.

[0014] In one embodiment, the number of the core phase distribution flow channels and the shell phase distribution flow channels is the same, and is any number between 2 and 24. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The present invention will be further described below with reference to the accompanying drawings and embodiments, in which: Figure 1 A schematic diagram of a portion of the structure of a core-shell hydrogel microsphere preparation device according to one embodiment; Figure 2 A schematic diagram of a portion of the structure of a core-shell hydrogel microsphere preparation device according to one embodiment; Figure 3 A schematic diagram of a portion of the structure of a core-shell hydrogel microsphere preparation device according to one embodiment; Figure 4 A cross-sectional view of a partial structure of a core-shell hydrogel microsphere preparation device according to an embodiment; Figure 5 A schematic diagram of a portion of the structure of a core-shell hydrogel microsphere preparation device according to one embodiment; Figure 6 A schematic diagram of a portion of the structure of a core-shell hydrogel microsphere preparation device according to one embodiment; Figure 7 A cross-sectional view of a partial structure of a core-shell hydrogel microsphere preparation device according to one embodiment.

[0016] Figure numerals: core-shell hydrogel microsphere preparation equipment 10; microsphere preparation device 20; core phase inlet 21; shell phase inlet 22; core phase distribution channel 23; shell phase distribution channel 24; coaxial channel 25; central core phase channel 251; annular shell phase channel 252; inner conical core phase outlet 253; outer conical shell phase outlet 254; microsphere collecting device 30; microsphere collecting pool 31; inner cavity 32; liquid level adjustment cavity 33; notch 34. DETAILED DESCRIPTION

[0017] This section will describe in detail the specific embodiments of the present invention. The preferred embodiments of the present invention are shown in the accompanying drawings. The purpose of the accompanying drawings is to supplement the description of the text part of the specification with graphics, so that people can intuitively and vividly understand each technical feature and the overall technical solution of the present invention, but it should not be understood as a limitation on the scope of protection of the present invention.

[0018] In the description of this invention, "above," "below," and "within" are understood to be exclusive of the number indicated. The terms "first" and "second" are used solely to distinguish technical features and are not to be construed as indicating or implying relative importance, or as implicitly specifying the number or order of the technical features indicated.

[0019] In the present invention, unless otherwise expressly specified or limited, when a first feature is "above" or "below" a second feature, it may mean that the first and second features are in direct contact, or that the first and second features are in indirect contact through an intermediary. Furthermore, when a first feature is "above," "above," or "above" a second feature, it may mean that the first feature is directly above or diagonally above the second feature, or simply means that the first feature is at a higher level than the second feature. When a first feature is "below," "below," or "below" a second feature, it may mean that the first feature is directly below or diagonally below the second feature, or simply means that the first feature is at a lower level than the second feature.

[0020] In the present invention, unless otherwise expressly defined, terms such as "disposed," "installed," and "connected" should be interpreted broadly. For example, they may refer to direct connection or indirect connection through an intermediate medium; fixed connection or detachable connection or integral molding; mechanical connection; and internal communication between two components or interaction between two components. Those skilled in the art can reasonably determine the specific meanings of these terms in the present invention based on the specific content of the technical solution.

[0021] Droplet microfluidics offers the feasibility of processing microdroplets and cross-linked microspheres of extremely small volumes (from microliters to femtoliters), leading to extensive research and application in diverse fields, including materials science and biomedicine. In droplet microfluidics, microdroplets are typically generated by shear between immiscible liquid phases under specific configurations (coaxial flow, flow focusing, and cross-flow). These droplets can vary significantly depending on the interaction of flow rate, fluid properties, and specially designed microchannel geometry. Traditional microfluidic chip-based droplet microfluidics typically requires cumbersome microfluidic device fabrication, hydrophilic and hydrophobic modification of microchannels, and specialized equipment, increasing cost and complexity and hindering large-scale application. Furthermore, the size and monodispersity of microspheres generated using droplet microfluidic chips are significantly affected by the flow rate and physical properties of the fluids; even slight fluctuations in these properties can lead to uncontrolled size variations in the droplet products. These technologies also often rely on surfactants to assist droplet formation, which can hinder the application of droplet microfluidics in certain areas, such as live cell encapsulation. The current process for preparing core-shell hydrogel microspheres based on traditional microfluidic chips is limited by the strong correlation between fluid flow rate and ball formation effect, and it is difficult to improve production efficiency by directly increasing the fluid flow rate. The linear array device derived from the technology of wetting-induced interface destruction to form balls at the gas-liquid interface cannot form core-shell microspheres with uniform and stable shell thickness, and it is difficult to improve the production efficiency of core-shell microspheres by increasing the number of microdroplet outlets. These problems limit the stable large-scale production of core-shell hydrogel microspheres and hinder the transformation of a large number of related scientific research results into market products. Therefore, there is an urgent need to develop a device that can stably achieve high-throughput preparation of core-shell hydrogel microspheres.

[0022] See Figures 1 to 7 To solve the above problems, the embodiment of the present application provides a core-shell hydrogel microsphere preparation device 10, comprising: a microsphere preparation device 20, provided with a core phase inlet 21, a shell phase inlet 22, a plurality of core phase distribution flow channels 23 connected to the core phase inlet 21, and a plurality of shell phase distribution flow channels 24 connected to the shell phase inlet 22, the core phase distribution flow channels 23 and the shell phase distribution flow channels 24 correspondingly merging at the end into a coaxial flow channel 25; a microsphere collection device 30, comprising a microsphere collection pool 31, the microsphere collection pool 31 is arranged below the coaxial flow channel 25, and the microsphere collection pool 31 is used to place the oil phase fluid; the core phase fluid entering from the core phase inlet 21 and the shell phase fluid entering from the shell phase inlet 22 form a stratified fluid at the coaxial flow channel 25 and drip into the microsphere collection pool 31.

[0023] Specifically, in this embodiment, the core-shell hydrogel microsphere preparation device 10 includes a microsphere preparation device 20 and a microsphere collection device 30. The microsphere preparation device 20 is used for forming core-shell microspheres, and the microsphere collection device 30 is used to receive, solidify and collect the formed core-shell microspheres. Specifically, the microsphere preparation device 20 is provided with a core phase inlet 21, a shell phase inlet 22, a plurality of core phase distribution flow channels 23 and a plurality of shell phase distribution flow channels 24. The plurality of core phase distribution flow channels 23 are connected to the core phase inlet 21, and the plurality of shell phase distribution flow channels 24 are connected to the shell phase inlet 22. The microsphere preparation device 20 adopts a dual-channel fluid input design, with independent core phase inlet 21 and shell phase inlet 22, which are used to inject core material and coating material solutions, respectively. In some embodiments, the core phase inlet 21 and the shell phase inlet 22 are cylindrical structures with an outer diameter set to 0.5 mm to 3 mm, an inner diameter set to 0.2 mm to 2 mm, and a length set to 1.5 mm to 5 mm. The core phase distribution channel 23 is a key structure in the microsphere preparation device 20. It can evenly distribute the core phase fluid, diverting the core material (such as drug solution, cell suspension, etc.) entering from the core phase inlet 21 to multiple symmetrical core phase distribution channels 23, ensuring consistent core phase flow at each outlet, avoiding microsphere size differences caused by uneven distribution, and maintaining stable flow of the core phase fluid. By optimizing the channel size and path, fluid resistance is reduced, preventing flow rate fluctuations or blockages during the core phase transportation process, and ensuring the integrity of the core-shell structure. The shell phase distribution channel 24 works in conjunction with the core phase distribution channel 23 to divert the coating material (such as hydrogel precursor) entering from the shell phase inlet 22 to the channel corresponding to the core phase channel. The core phase distribution channel 23 and the shell phase distribution channel 24 correspond one-to-one and merge at the end to form a coaxial channel 25. At the end of the channel, the core phase fluid is precisely guided to the center of the coaxial channel 25 to ensure that it is evenly wrapped by the shell phase fluid, forming a standard core-shell structure. The shell phase distribution channel 24 corresponds to the core phase distribution channel 23 one by one to ensure precise packaging. Specifically, the shell phase distribution channel 24 and the core phase distribution channel 23 adopt a symmetrical design. Each core phase channel corresponds to a shell phase channel, so that the core-shell fluid forms a stable coaxial flow when it converges at the end. Multiple channels work in parallel and can generate multiple core-shell microspheres at the same time, which greatly improves the output compared to single-channel microfluidic chips. At the same time, through precision processing and fluid control, the fluid behavior of all channels is ensured to be consistent, so that the core-shell structure of the entire batch of microspheres is highly uniform. The core phase distribution channel 23 and the shell phase distribution channel 24 can realize the distribution and packaging of the core-shell fluid, ensuring the structural integrity, size uniformity and controllability of the microspheres.

[0024] Furthermore, in this embodiment, the microsphere collection device 30 includes a microsphere collection pool 31. The main function of the microsphere collection device 30 is to receive, solidify and collect the formed core-shell microspheres. After the microspheres drip from the coaxial flow channel 25, they enter the collection pool filled with an oil phase medium (such as mineral oil, silicone oil, etc.). The oil phase needs to have appropriate viscosity and surface tension to ensure that the droplets can maintain a spherical shape when contacting the oil phase and avoid damage to the core-shell structure. In some embodiments, the microsphere collection pool 31 is a hollow cylindrical structure, the outer diameter can be set to 6 to 20 mm, the inner diameter can be set to 1 mm to 5 mm, the outer wall thickness can be set to 0.2 mm to 1 mm, the height can be set to 8 mm to 15 mm, the inner wall thickness can be set to 0.1 mm to 0.6 mm, and the height can be set to 7 mm to 16.5 mm.

[0025] Furthermore, the coaxial flow channel 25 includes a central core phase channel 251 and an annular shell phase channel 252. The coaxial flow channel 25 adopts a composite channel structure and is a key component for achieving precise molding of core-shell microspheres. The coaxial flow channel 25 is composed of a central core phase channel 251 and an outer annular shell phase channel 252 to form a coaxial nested fluid passage. Specifically, the annular shell phase channel 252 surrounds the outside of the central core phase channel 251, the central core phase channel 251 is connected to the core phase distribution flow channel 23, and the annular shell phase channel 252 is connected to the shell phase distribution flow channel 24. In one embodiment, the central core phase channel 251 is a straight cylindrical structure, which is directly connected to the upstream core phase distribution flow channel 23 and is responsible for stably transporting the core material fluid to the dripping position. Surrounding the outside of the central channel is the annular shell phase channel 252, which has a uniform circular cross-section and seamlessly connects with the shell phase distribution flow channel 24. The annular shell phase channel 252 can adopt a tapered design, with a wider inlet end to receive shell phase fluid from multiple directions, and the outlet end gradually narrows to form a uniform shell phase wrapping layer. The inner surface of the channel is hydrophobic treated to effectively reduce fluid resistance and prevent material adhesion. In some embodiments, the diameter of the central core phase channel 251 can be set to 0.3mm to 0.9mm, and the diameter of the annular shell phase channel 252 can be set to 0.5mm to 2mm, wherein the wall thickness of the central core phase channel 251 can be set to 0.04mm to 0.2mm, and the length can be set to 1.5mm to 7mm, and the wall thickness of the annular shell phase channel 252 can be set to 0.04mm to 0.5mm, and the length can be set to 1mm to 6mm.

[0026] The central core phase channel 251 and the annular shell phase channel 252 form a precise coaxial docking structure at the end. In one embodiment, the outlet of the central core phase channel 251 slightly protrudes from the annular shell phase channel 252 to ensure that the core phase fluid can be completely wrapped without mixing with the shell phase in advance, so that the core phase and shell phase fluids always maintain a clear interface stratification before dripping, thereby ensuring that the finally formed microspheres have a core-shell structure that meets the requirements.

[0027] Furthermore, in this embodiment, the coaxial flow channel 25 includes an inner conical core phase outlet 253 and an outer conical shell phase outlet 254. The coaxial flow channel 25 is designed to be precisely combined with the inner and outer conical outlets to form a nested fluid passage structure. The outer conical shell phase outlet 254 is coaxially arranged with the inner conical core phase outlet 253. The end of the core phase distribution flow channel 23 is connected to the inner conical core phase outlet 253, and the end of the shell phase distribution flow channel 24 is connected to the outer conical shell phase outlet 254. In one embodiment, the inner conical core phase outlet 253 adopts a tapered design, and its tapered angle can guide the core phase fluid to smoothly transition and focus to the outlet tip. The tapered structure can effectively reduce the shear force of the fluid at the outlet, protecting sensitive bioactive substances from damage. Furthermore, the outer conical shell phase outlet 254 also adopts a precision-machined conical structure, maintaining a strict coaxial alignment relationship with the inner core phase outlet. Its taper design is slightly slower than the inner outlet, forming a uniform annular gap, so that the shell phase fluid can form a uniform wrapping layer on the periphery of the inner core phase fluid, achieving a core-shell wrapping effect. The end positions of the two conical outlets are calibrated to ensure that the core phase fluid contacts the shell phase fluid only when it is about to drip, avoiding premature mixing that affects the quality of the microspheres. The above-mentioned coaxial flow channel 25 supports a variety of fluid combinations of viscosities, and can operate stably from low-viscosity aqueous solutions to high-viscosity polymer precursors. The unique self-cleaning properties of the conical structure can effectively prevent material accumulation and clogging, greatly extending the continuous operation time. In some embodiments, the inner conical core phase outlet 253 can have a diameter of 0.05 mm to 0.4 mm, a length of 0.5 mm to 1 mm, and a wall thickness of 0.04 mm to 0.5 mm. The outer conical shell phase outlet 254 can have a diameter of 0.2 mm to 1 mm, a length of 0.7 mm to 1.5 mm, and a wall thickness of 0.04 mm to 0.5 mm. In some embodiments, the distance between the inner conical core phase outlet 253 and the outer conical shell phase outlet 254 is 0.2 mm to 1 mm.

[0028] In some embodiments, the core phase distribution flow channel 23 and the shell phase distribution flow channel 24 correspond one to one in the height direction, the core phase distribution flow channel 23 extends radially along the core phase inlet 21, and the shell phase distribution flow channel 24 extends radially along the shell phase inlet 22. In the vertical spatial layout, the core phase distribution flow channel 23 and the shell phase distribution flow channel 24 adopt a stacked correspondence. Each set of core phase and shell phase flow channels are precisely aligned in the height direction to form a fluid transport unit that echoes each other up and down. This three-dimensional layout design not only optimizes the equipment space utilization, but more importantly, ensures that the core phase and shell phase fluids can arrive at the confluence point synchronously. The core phase distribution flow channel 23 starts from the core phase inlet 21 and is evenly distributed radially along the radial direction. Each flow channel adopts a gradient cross-section design, with the inlet end being wider to reduce flow resistance and the outlet end gradually narrowing to increase fluid velocity. The inner wall of the flow channel has excellent surface smoothness, which can minimize energy loss during fluid flow. Similarly, the shell-phase distribution channels 24 are arranged radially, symmetrically outward from the shell-phase inlet 22. While parallel to the core-phase channels, they are spatially offset by a certain distance, creating a distinct layer of fluid transport. This design ensures the independence of the two fluids while facilitating their subsequent coaxial convergence.

[0029] In some embodiments, each core phase distribution channel 23 is arranged in a circumferential periodic pattern relative to the core phase inlet 21, and each shell phase distribution channel 24 is arranged in a circumferential periodic pattern relative to the shell phase inlet 22. The circumferential periodic layout design ensures the uniformity and stability of fluid distribution, providing a reliable guarantee for the uniform preparation of core-shell microspheres. The core phase distribution channel 23 system takes the core phase inlet 21 as the center point and adopts a symmetrical radial distribution pattern. Each core phase flow channel starts from the central inlet and extends evenly along the radial path, forming a perfect star array in three-dimensional space. The symmetrical layout ensures that the core phase fluid dispersed from the center point can be evenly distributed to each outlet, avoiding the problem of uneven flow caused by differences in flow channel position. Similarly, the shell phase distribution channel 24 system also follows the principle of circumferential periodicity, radiating outward with the shell phase inlet 22 as the center. All shell phase flow channels are consistent in spatial angle and extension length, forming a highly ordered annular distribution network. This design ensures that the coating material can be evenly delivered to each coaxial flow channel 25 interface. The two flow channel systems are spatially coordinated, maintaining their independence while also forming a synergistic relationship. The symmetrically designed flow channel system is self-balancing, automatically compensating for changes in fluid viscosity or pressure fluctuations, ensuring highly consistent fluid parameters at each outlet.

[0030] Furthermore, in this embodiment, the microsphere collection device 30 includes an inner cavity 32, which is connected to the shell phase inlet 22. The inner cavity 32 has a cylindrical or conical structure and is coaxial with the outer shell. In some embodiments, the liquid does not need to flow within the inner cavity 32. The inner cavity 32 can provide a channel for the pipeline, allowing the pipeline to be connected to the core phase inlet 21 without severe folding. Each additional device that the fluid directly contacts increases the risk of contamination. The provision of the inner cavity 32 can reduce contamination during the preparation process.

[0031] In some embodiments, the microsphere collection device 30 includes a liquid level adjustment chamber 33, and the top of the microsphere collection pool 31 is connected to the liquid level adjustment chamber 33 through a notch 34, thereby achieving automatic and stable control of the oil phase liquid level. The connection between the microsphere collection pool 31 and the adjustment chamber adopts a transition structure design, and the size of the notch 34 has been calculated by fluid mechanics, which can not only ensure the free flow of liquid, but also effectively prevent the microspheres from accidentally entering the adjustment chamber. In some embodiments, the width of the notch 34 is 1.5mm to 4mm, and the vertical distance between the bottom of the notch 34 and the top of the inner wall of the microsphere collection pool 31 is 1.5mm to 4mm. In one embodiment, the change in the total volume of the microsphere collection pool 31 will cause the total volume to increase due to the microspheres entering the pool. Therefore, in order to achieve the constant liquid level height of the microsphere collection pool 31, it is necessary to allow the oil phase of the microsphere volume to enter the control pool from the microsphere collection pool 31, that is, after the liquid level rises, the excess liquid flows into the control pool through the notch 34, and the control pool can be empty initially. This design eliminates the inconvenience of the traditional collection device requiring manual frequent adjustment of the liquid level, and achieves long-term stable automatic operation. In some embodiments, the liquid level adjustment chamber 33 is equipped with a visual liquid level indicator, allowing operators to monitor the system status in real time. The chamber is constructed of corrosion-resistant materials to prevent the oil phase from adhering to and remaining in the chamber. The sealing performance of the entire system has been rigorously tested to ensure long-term leakage protection.

[0032] In some embodiments, the core-shell hydrogel microsphere preparation device 10 also includes a light-curing component, which is located on the side of the microsphere collection device 30 and adopts a modular design for easy installation and maintenance. The light-curing component integrates a high-performance light source system, which can provide ultraviolet light or visible light of specific wavelengths according to the curing requirements of different hydrogel materials. The light source has undergone professional optical design and is combined with a precise reflective system and a uniform light device to ensure uniform light distribution and avoid local over-intensity or under-intensity. At least part of the microsphere collection device 30 is a light-transmitting structure, and the light-curing component illuminates the microsphere collection pool 31 through the light-transmitting structure. Specific areas of the collection pool are made of highly transparent materials to form high-quality light-transmitting windows. This light-transmitting structure has been specially treated to have extremely high light transmittance and excellent weather resistance, and can maintain stable optical properties for a long time. The size and position of the light-transmitting area can be designed according to actual needs to ensure that the curing light can fully cover the entire microsphere formation area. The light-curing component irradiates the microspheres in the collection pool in all directions through the light-transmitting structure. The light penetrates the transparent curing medium and directly acts on the hydrogel microspheres, initiating the material's photocross-linking reaction. This irradiation method avoids the shadowing effects that can occur with traditional top-down irradiation, ensuring uniform light intensity for each microsphere and achieving consistent curing results. The light-curing component not only improves the curing efficiency of the microspheres but also ensures the integrity and stability of the core-shell structure. Through precisely controlled illumination conditions, the hydrogel material exhibits excellent mechanical and functional properties.

[0033] Furthermore, in this embodiment, the number of core phase distribution channels 23 and shell phase distribution channels 24 is the same, and both are any number between 2 and 24. The modular design of the number of channels fully takes into account the process requirements of production on different scales, providing users with a wide range of application adaptability. In the standard configuration, the core phase distribution channels 23 and the shell phase distribution channels 24 always maintain a one-to-one correspondence in quantity, ensuring that each core phase channel can obtain a matching shell phase wrapping channel. The symmetrical design of the number of channels is the key to the efficient preparation of core-shell microspheres in this device. It ensures that the core phase material can be evenly and completely wrapped to form microspheres with consistent structure. The lower limit of the number of channels is set to 2, and this configuration can meet the needs of laboratory research and development and small-batch trial production. The 2-channel design reduces the complexity of the equipment and maintenance costs while ensuring basic production efficiency, and is particularly suitable for experimental verification work in the process development stage. Each channel has been optimized to ensure uniform distribution of the fluid even in the minimum configuration. The upper limit of the number of channels is extended to 24, and this configuration is aimed at industrial mass production needs. The parallel operation of 24 flow channels can significantly increase the equipment's production capacity and meet the stringent requirements of large-scale production. When multiple flow channels work together, the system uses a precise fluid balance design to ensure that the flow and pressure of each channel remain highly consistent, avoiding product quality fluctuations caused by the increase in the number of flow channels. Within the range of 2 to 24, users can choose an intermediate number of flow channel configurations such as 8, 12, 16, and 20 according to specific production needs. Each configuration has undergone rigorous fluid dynamics verification to ensure operational stability at different numbers. The equipment adopts a standardized interface design, and the number of flow channels can be adjusted by replacing modules, which is simple and quick to operate.

[0034] In some embodiments, the microsphere collection device 30 can control the height of the inner wall of the microsphere collection pool 31, control the distance from the outlet of the microspheres of the microsphere preparation device 20 to the liquid surface of the oil phase fluid in the microsphere collection pool 31 of the microsphere collection device 30, and thus control the diameter of the core-shell hydrogel microspheres, so as to simply change the height of the support structure of the microsphere collection pool 31, control the distance from the inner conical core phase outlet 253 and the outer conical shell phase outlet 254 to the liquid surface of the microsphere collection pool 31, and adjust the overall size of the core-shell microspheres.

[0035] In one embodiment, in the core-shell hydrogel microsphere preparation device 10, the microsphere preparation device 20 made of biocompatible material is first horizontally installed above the microsphere collection device 30, and the oil phase medium containing acetic acid is injected into the microsphere collection pool 31 and the fluid pipeline is connected. During preparation, the sodium alginate shell phase fluid and the core phase fluid respectively enter the corresponding liquid separation pool, and after being evenly distributed by the symmetrically distributed flow channel system, a layered fluid is formed at the end of the coaxial flow channel 25. When the composite fluid drips into the oil phase from the microsphere outlet, the calcium carbonate nanoparticles in the shell layer react with acetic acid to generate calcium ions, which promote the rapid cross-linking and curing of sodium alginate to form a core-shell structure. Finally, the oil phase is removed by centrifugal washing to obtain uniformly dispersed core-shell hydrogel microspheres, which are easy to store and use after freeze-drying. The entire process realizes continuous automated production from fluid distribution to microsphere curing, ensuring that the product has good consistency and repeatability.

[0036] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention shall be determined by the appended claims.

Claims

1. A core-shell hydrogel microsphere preparation device, characterized in that: include: A microsphere preparation device is provided with a core phase inlet, a shell phase inlet, a plurality of core phase distribution flow channels connected to the core phase inlet, and a plurality of shell phase distribution flow channels connected to the shell phase inlet, wherein the core phase distribution flow channels and the shell phase distribution flow channels correspond to each other and merge into a coaxial flow channel at the end; A microsphere collecting device, comprising a microsphere collecting pool, the microsphere collecting pool being disposed below the coaxial flow channel and being used to place the oil phase fluid; The core phase fluid entering through the core phase inlet and the shell phase fluid entering through the shell phase inlet form a layered fluid at the coaxial flow channel and drip into the microsphere collection pool.

2. The core-shell hydrogel microsphere preparation device according to claim 1, characterized in that: The coaxial flow channel includes a central core phase channel and an annular shell phase channel. The annular shell phase channel surrounds the outside of the central core phase channel. The central core phase channel is connected to the core phase distribution flow channel, and the annular shell phase channel is connected to the shell phase distribution flow channel.

3. The core-shell hydrogel microsphere preparation device according to claim 1, characterized in that: The coaxial flow channel includes an inner conical core phase outlet and an outer conical shell phase outlet, and the outer conical shell phase outlet is coaxially arranged with the inner conical core phase outlet; the end of the core phase distribution flow channel is connected to the inner conical core phase outlet, and the end of the shell phase distribution flow channel is connected to the outer conical shell phase outlet.

4. The core-shell hydrogel microsphere preparation device according to claim 1, characterized in that: The core phase distribution flow channel corresponds to the shell phase distribution flow channel in a one-to-one manner in the height direction. The core phase distribution flow channel extends radially of the core phase inlet, and the shell phase distribution flow channel extends radially of the shell phase inlet.

5. The core-shell hydrogel microsphere preparation device according to claim 4, characterized in that: Each of the core phase distribution flow channels is arranged circumferentially and periodically relative to the core phase inlet, and each of the shell phase distribution flow channels is arranged circumferentially and periodically relative to the shell phase inlet.

6. The core-shell hydrogel microsphere preparation device according to claim 1, characterized in that: The microsphere collection device includes an inner cavity, which is communicated with the shell phase inlet.

7. The core-shell hydrogel microsphere preparation device according to claim 1, characterized in that: The microsphere collecting device comprises a liquid level regulating cavity, and the top of the microsphere collecting pool is communicated with the liquid level regulating cavity through a notch.

8. The core-shell hydrogel microsphere preparation device according to claim 7, characterized in that: The liquid level regulating chamber maintains the height of the solidified medium liquid level in the microsphere collecting pool by regulating the volume of the chamber.

9. The core-shell hydrogel microsphere preparation device according to claim 1, characterized in that: It also includes a light curing component, which is arranged on the side of the microsphere collection device. At least part of the microsphere collection device is a light-transmitting structure, and the light curing component irradiates the microsphere collection pool through the light-transmitting structure.

10. The core-shell hydrogel microsphere preparation device according to claim 1, characterized in that: The number of the core phase distribution flow channels and the shell phase distribution flow channels is the same, and is any number between 2 and 24.

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