Core-shell hydrogel microsphere preparation equipment

By designing a core-shell hydrogel microsphere preparation device and employing a multi-channel coaxial flow channel and photocuring components, the problem of high-throughput preparation of core-shell hydrogel microspheres in traditional methods has been solved, achieving efficient and uniform production of core-shell microspheres and promoting their industrial application in drug delivery and cell therapy.

CN120695751BActive Publication Date: 2025-11-14QINGYUAN ZHIXIN (SHENZHEN) BIOTECHNOLOGY CO LTD
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Patent Information

Application Number
CN202511196371.6
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2025-08-26
Publication Date
2025-11-14
Estimated Expiration
2045-08-26

AI Technical Summary

Technical Problem

Existing technologies make it difficult to achieve high-throughput preparation of core-shell hydrogel microspheres. Traditional microfluidic methods are limited by flow rate sensitivity and cannot achieve high-throughput production. Novel linear array technologies cannot guarantee the uniformity of the core-shell structure, which hinders their industrial application in drug delivery and cell therapy.

Method used

A core-shell hydrogel microsphere preparation device is designed, which employs a microsphere preparation device and a microsphere collection device. Multiple core and shell phase distribution channels are used to form a layered fluid at the coaxial channel to ensure consistent fluid behavior. A coaxial channel and a conical outlet structure are used to form stable core-shell microspheres. An oil phase medium is used to maintain the shape of the microspheres, and the microspheres are cured by a photocuring component.

Benefits of technology

High-throughput preparation of core-shell hydrogel microspheres has been achieved, ensuring high uniformity of the core-shell structure of the microspheres, improving production efficiency and product quality, and making them suitable for drug delivery and cell therapy.

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Abstract

This invention relates to a core-shell hydrogel microsphere preparation apparatus, comprising a microsphere preparation device and a microsphere collection device. The microsphere preparation device has a core phase inlet, a shell phase inlet, multiple core phase distribution channels communicating with the core phase inlet, and multiple shell phase distribution channels communicating with the shell phase inlet. The core phase distribution channels and shell phase distribution channels converge at their respective ends to form a coaxial channel. The microsphere collection device includes a microsphere collection pool disposed below the coaxial channel, which is used to hold 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 stratified fluid at the coaxial channel and drip into the microsphere collection pool. The core-shell hydrogel microsphere preparation apparatus provided in this application can achieve high-throughput preparation of core-shell hydrogel microspheres.
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Description

Technical Field

[0001] This invention relates to the field of droplet microfluidics, and in particular to a device for preparing core-shell hydrogel microspheres. Background Technology

[0002] Droplet microfluidics, with its advantages in manipulating droplets from microliter to femtoliter, has shown broad application prospects in materials science and biomedicine. 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 scaling up. While emerging microsphere generation technologies based on wetting-induced interface disruption have overcome flow rate limitations and simplified equipment structures, inconsistent flow rate ratios at multiple outlets in core-shell microsphere preparation lead to uneven shell thickness, failing to meet high-quality production requirements. In existing technologies, traditional microfluidic methods are limited by flow rate sensitivity, hindering high-throughput production, while novel linear array technologies cannot guarantee the uniformity of the core-shell structure. This dilemma severely restricts the industrial application of core-shell hydrogel microspheres in drug delivery, cell therapy, and other fields, necessitating the development of a device capable of high-throughput preparation of core-shell hydrogel microspheres. Summary of the Invention

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

[0004] An apparatus for preparing core-shell hydrogel microspheres, comprising:

[0005] The microsphere preparation apparatus includes a core phase inlet, a shell phase inlet, multiple core phase distribution channels communicating with the core phase inlet, and multiple shell phase distribution channels communicating with the shell phase inlet. The core phase distribution channels and the shell phase distribution channels are connected at their respective ends to form a coaxial channel.

[0006] A microsphere collection device includes a microsphere collection pool disposed below the coaxial flow channel, wherein the microsphere collection pool is used to hold oil phase fluid;

[0007] The nucleus fluid entering through the nucleus inlet and the shell fluid entering through the shell inlet form a stratified fluid at the coaxial flow channel and drip into the microsphere collection pool.

[0008] The above-described core-shell hydrogel microsphere preparation equipment has a core phase inlet and a shell phase inlet, used for injecting the core material and coating material solutions, respectively. Each core phase channel corresponds to a shell phase channel, allowing the core and shell fluids to converge at the end to form a stable coaxial flow. Multiple channels operate in parallel, enabling the simultaneous generation of multiple core-shell microspheres, significantly increasing yield compared to single-channel microfluidic chips. Simultaneously, through precision machining and fluid control, consistent fluid behavior across all channels is ensured, resulting in a highly uniform core-shell structure for the entire batch of microspheres. Core and shell phase distribution channels enable the distribution and encapsulation of the core and shell fluids. A microsphere collection device receives and collects the formed core-shell microspheres. After dripping from the coaxial channels, the microspheres enter a collection pool containing an oil phase medium (such as mineral oil or silicone oil). The microsphere collection device ensures that the droplets maintain their spherical shape upon contact with the oil phase, preventing damage to the core-shell structure.

[0009] In one embodiment, the coaxial flow channel includes a central nucleus phase channel and an annular shell phase channel. The annular shell phase channel surrounds the outside of the central nucleus phase channel. The central nucleus phase channel is connected to the nucleus phase distribution channel, and the annular shell phase channel is connected to the shell phase distribution channel.

[0010] In one embodiment, the coaxial flow channel includes an inner conical nucleus phase outlet and an outer conical shell phase outlet, wherein the outer conical shell phase outlet and the inner conical nucleus phase outlet are coaxially arranged; the end of the nucleus phase distribution flow channel is connected to the inner conical nucleus phase outlet, and the end of the shell phase distribution flow channel is connected to the outer conical shell phase outlet.

[0011] In one embodiment, the nucleus distribution channel and the shell distribution channel correspond one-to-one in the height direction, the nucleus distribution channel extends radially along the nucleus inlet, and the shell distribution channel extends radially along the shell inlet.

[0012] In one embodiment, each of the core phase distribution channels is arranged in a circumferential periodic manner relative to the core phase inlet, and each of the shell phase distribution channels is arranged in a circumferential periodic manner relative to the shell phase inlet.

[0013] In one embodiment, the microsphere collecting device includes an inner cavity that communicates with the shell inlet.

[0014] In one embodiment, the microsphere collecting device includes a liquid level adjustment chamber, and the top of the microsphere collecting pool is connected to the liquid level adjustment chamber through a notch.

[0015] In one embodiment, the liquid level adjustment chamber maintains the height of the solidified medium liquid level in the microsphere collection pool by adjusting the volume of the chamber.

[0016] In one embodiment, a photocuring component is also included, which is disposed on the side of the microsphere collecting device. At least a portion of the microsphere collecting device is a light-transmitting structure, and the photocuring component illuminates the microsphere collecting pool through the light-transmitting structure.

[0017] In one embodiment, the number of core phase distribution channels and shell phase distribution channels is the same, and each has any number from 2 to 24. Attached Figure Description

[0018] The present invention will be further described below with reference to the accompanying drawings and embodiments, wherein:

[0019] Figure 1 This is a partial structural schematic diagram of a core-shell hydrogel microsphere preparation device according to an embodiment;

[0020] Figure 2 This is a partial structural schematic diagram of a core-shell hydrogel microsphere preparation device according to an embodiment;

[0021] Figure 3 This is a partial structural schematic diagram of a core-shell hydrogel microsphere preparation device according to an embodiment;

[0022] Figure 4 A cross-sectional view of a partial structure of a core-shell hydrogel microsphere preparation apparatus according to an embodiment;

[0023] Figure 5 This is a partial structural schematic diagram of a core-shell hydrogel microsphere preparation device according to an embodiment;

[0024] Figure 6 This is a partial structural schematic diagram of a core-shell hydrogel microsphere preparation device according to an embodiment;

[0025] Figure 7 This is a cross-sectional view of a partial structure of a core-shell hydrogel microsphere preparation device according to an embodiment.

[0026] Figure reference numerals: 10 Core-shell hydrogel microsphere preparation equipment; 20 Microsphere preparation device; 21 Core phase inlet; 22 Shell phase inlet; 23 Core phase distribution channel; 24 Shell phase distribution channel; 25 Coaxial channel; 251 Central core phase channel; 252 Annular shell phase channel; 253 Inner conical core phase outlet; 254 Outer conical shell phase outlet; 30 Microsphere collection device; 31 Microsphere collection pool; 32 Inner cavity; 33 Liquid level adjustment cavity; 34 Notch. Detailed Implementation

[0027] This section will describe in detail specific embodiments of the present invention. Preferred embodiments of the present invention are shown in the accompanying drawings. The purpose of the drawings is to supplement the textual description with graphics, so that people can intuitively and vividly understand each technical feature and overall technical solution of the present invention, but they should not be construed as limiting the scope of protection of the present invention.

[0028] In the description of this invention, "multiple" means two or more; "greater than," "less than," and "exceeding" are understood to exclude the stated number; "above," "below," and "within" are understood to include the stated number. The use of "first" and "second" in the description is merely for distinguishing technical features and should not be construed as indicating or implying relative importance, or implicitly indicating the number of indicated technical features, or implicitly indicating the order of the indicated technical features.

[0029] In this invention, unless otherwise explicitly specified and limited, "above" or "below" the second feature can mean that the first feature is in direct contact with the second feature, or that the first feature is in indirect contact with the second feature through an intermediate medium. Furthermore, "above," "over," and "on top" of the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply that the first feature is at a lower horizontal level than the second feature.

[0030] In this invention, unless otherwise explicitly defined, the terms "setting," "installing," and "connecting" should be interpreted broadly. For example, they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to a fixed connection, a detachable connection, or an integrally formed connection; they can refer to a mechanical connection; they can refer to the internal connection of two components or the interaction between two components. Those skilled in the art can reasonably determine the specific meaning of the above terms in this invention in conjunction with the specific content of the technical solution.

[0031] Droplet microfluidics offers the feasibility of processing microdroplets and cross-linked microspheres with extremely small volumes (microliter to femtoliter), leading to its widespread research and application in materials science, biomedicine, and other fields. In droplet microfluidics, microdroplets are typically generated by fluid shearing between immiscible liquid phases under specific structural conditions (coaxial flow, flow focusing, and crossflow), and their size varies significantly depending on the combined effects of flow rate, fluid properties, and specially designed microchannel geometry. Traditional microfluidic chip-based droplet microfluidics usually requires complex microfluidic device manufacturing processes, hydrophilic / hydrophobic modification of microchannels, and additional support from specialized equipment, increasing cost and complexity and hindering large-scale applications. Furthermore, the size and monodispersity of microspheres generated by droplet microfluidic chips are greatly influenced by fluid flow rate and physical properties; even slight fluctuations in flow rate and physical properties can lead to uncontrollable size changes in the droplet product. These technologies often rely heavily on surfactants to assist droplet formation, which may impede the application of droplet microfluidics in certain fields, such as live cell encapsulation. Current processes for fabricating core-shell hydrogel microspheres based on traditional microfluidic chips are limited by the strong correlation between fluid flow rate and spheroidization effect, making it difficult to improve production efficiency by directly increasing the fluid flow rate. Linear array devices derived from wetting-induced interface disruption techniques to form microspheres at the gas-liquid interface cannot form core-shell microspheres with uniform and stable shell thickness, making it difficult to improve production efficiency 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 numerous related research results into marketable products. Therefore, there is an urgent need to develop a device capable of stably achieving high-throughput fabrication of core-shell hydrogel microspheres.

[0032] See Figures 1-7 To address the aforementioned issues, this application provides a core-shell hydrogel microsphere preparation device 10, comprising: a microsphere preparation apparatus 20, having a core phase inlet 21, a shell phase inlet 22, a plurality of core phase distribution channels 23 communicating with the core phase inlet 21, and a plurality of shell phase distribution channels 24 communicating with the shell phase inlet 22, wherein the core phase distribution channels 23 and the shell phase distribution channels 24 are correspondingly merged at their ends to form a coaxial channel 25; and a microsphere collection device 30, including a microsphere collection pool 31, which is disposed below the coaxial channel 25 and is used to hold oil phase fluid; the core phase fluid entering through the core phase inlet 21 and the shell phase fluid entering through the shell phase inlet 22 form a stratified fluid at the coaxial channel 25 and drip into the microsphere collection pool 31.

[0033] 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 for receiving, solidifying, and collecting the formed core-shell microspheres. Specifically, the microsphere preparation device 20 is provided with a core phase inlet 21, a shell phase inlet 22, multiple core phase distribution channels 23, and multiple shell phase distribution channels 24. The multiple core phase distribution channels 23 are connected to the core phase inlet 21, and the multiple shell phase distribution 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 inlets 21 and shell phase inlets 22, which are used for injecting core material and coating material solutions, respectively. In some embodiments, the core phase inlet 21 and shell phase inlet 22 are cylindrical structures with an outer diameter of 0.5 mm to 3 mm, an inner diameter of 0.2 mm to 2 mm, and a length of 1.5 mm to 5 mm. The core phase distribution channel 23 is a key structure in the microsphere preparation device 20. It can uniformly 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. This ensures that the core phase flow rate at each outlet is consistent, avoiding microsphere size differences due to 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 of the core phase during transport 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, diverting 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 channels 23 and shell phase distribution channels 24 converge at their ends 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, ensuring that it is uniformly coated by the shell phase fluid, forming a standard core-shell structure. The shell phase distribution channel 24 and the core phase distribution channel 23 correspond one-to-one to ensure precise encapsulation. Specifically, the shell phase distribution channel 24 and the core phase distribution channel 23 adopt a symmetrical design, with each core phase channel corresponding to one shell phase channel. This allows the core and shell fluids to form a stable coaxial flow when they converge at the end. Multiple channels working in parallel can simultaneously generate multiple core-shell microspheres, significantly increasing yield compared to single-channel microfluidic chips. Simultaneously, through precision machining and fluid control, consistent fluid behavior across all channels is ensured, resulting in a highly uniform core-shell structure throughout the batch of microspheres. The core phase distribution channel 23 and the shell phase distribution channel 24 enable the distribution and encapsulation of the core and shell fluids, ensuring the structural integrity, dimensional uniformity, and controllability of the microspheres.

[0034] Furthermore, in this embodiment, the microsphere collecting device 30 includes a microsphere collecting pool 31. The main function of the microsphere collecting 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 collecting pool containing 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 maintain their spherical shape when in contact with the oil phase and to avoid damage to the core-shell structure. In some embodiments, the microsphere collecting pool 31 is a hollow cylindrical structure with an outer diameter of 6 to 20 mm, an inner diameter of 1 mm to 5 mm, an outer wall thickness of 0.2 mm to 1 mm, a height of 8 mm to 15 mm, an inner wall thickness of 0.1 mm to 0.6 mm, and a height of 7 mm to 16.5 mm.

[0035] 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 jointly formed by the central core phase channel 251 and the outer annular shell phase channel 252, creating a coaxial nested fluid pathway. 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 channel 23, and the annular shell phase channel 252 is connected to the shell phase distribution channel 24. In one embodiment, the central core phase channel 251 has a straight cylindrical structure and is directly connected to the upstream core phase distribution channel 23, 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, whose cross-section is a uniform ring shape, seamlessly connecting with the shell phase distribution 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 a gradually narrowing outlet end to form a uniform shell-phase encapsulation layer. The inner surface of the channel is hydrophobically 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 0.3 mm to 0.9 mm, and the diameter of the annular shell-phase channel 252 can be set to 0.5 mm to 2 mm. The wall thickness of the central core-phase channel 251 can be set to 0.04 mm to 0.2 mm, and the length can be set to 1.5 mm to 7 mm. The wall thickness of the annular shell-phase channel 252 can be set to 0.04 mm to 0.5 mm, and the length can be set to 1 mm to 6 mm.

[0036] The central core phase channel 251 and the annular shell phase channel 252 form a precise coaxial docking structure at their ends. In one embodiment, the outlet of the central core phase channel 251 protrudes slightly beyond the annular shell phase channel 252 to ensure that the core phase fluid can be completely encapsulated without being mixed with the shell phase in advance. This ensures that the core phase and shell phase fluids maintain a clear interface layer before dripping, thereby guaranteeing that the final microspheres have a core-shell structure that meets the requirements.

[0037] Furthermore, in this embodiment, the coaxial flow channel 25 includes an inner conical nucleus phase outlet 253 and an outer conical shell phase outlet 254. The coaxial flow channel 25 is designed to be precisely combined from the inner and outer conical outlets, forming a nested fluid passage structure. The outer conical shell phase outlet 254 is coaxially arranged with the inner conical nucleus phase outlet 253. The end of the nucleus phase distribution channel 23 is connected to the inner conical nucleus phase outlet 253, and the end of the shell phase distribution channel 24 is connected to the outer conical shell phase outlet 254. In one embodiment, the inner conical nucleus phase outlet 253 adopts a tapered design, and its conical angle can guide the nucleus phase fluid to transition smoothly and focus to the outlet tip. The conical 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 employs a precision-machined conical structure, maintaining a strict coaxial alignment with the inner core-phase outlet. Its taper is slightly gentler than that of the inner outlet, forming a uniform annular gap. This allows the shell-phase fluid to form a uniform encapsulation layer around the inner core-phase fluid, achieving a core-shell encapsulation effect. The ends of the two conical outlets are calibrated to ensure that the core-phase fluid only contacts the shell-phase fluid just before dripping, avoiding premature mixing that could affect the microsphere quality. The aforementioned coaxial flow channel 25 supports fluid combinations of various viscosities, operating stably from low-viscosity aqueous solutions to high-viscosity polymer precursors. The unique self-cleaning properties of the conical structure effectively prevent material accumulation and clogging, significantly extending continuous operating time. In some embodiments, the diameter of the inner conical nucleus phase outlet 253 can be set to 0.05 mm to 0.4 mm, the length can be set to 0.5 mm to 1 mm, and the wall thickness can be set to 0.04 mm to 0.5 mm; the diameter of the outer conical shell phase outlet 254 can be set to 0.2 mm to 1 mm, the length can be set to 0.7 mm to 1.5 mm, and the wall thickness can be set to 0.04 mm to 0.5 mm. In some embodiments, the distance between the inner conical nucleus phase outlet 253 and the outer conical shell phase outlet 254 is 0.2 mm to 1 mm.

[0038] In some embodiments, the nucleus phase distribution channel 23 and the shell phase distribution channel 24 correspond one-to-one in the height direction. The nucleus phase distribution channel 23 extends radially along the nucleus phase inlet 21, and the shell phase distribution channel 24 extends radially along the shell phase inlet 22. In the vertical spatial layout, the nucleus phase distribution channel 23 and the shell phase distribution channel 24 adopt a stacked correspondence. Each set of nucleus and shell phase channels is precisely aligned in the height direction, forming a fluid transport unit that echoes each other vertically. This three-dimensional layout design not only optimizes the space utilization of the equipment, but more importantly, ensures that the nucleus and shell phase fluids can reach the confluence point synchronously. The nucleus phase distribution channel 23 starts from the nucleus phase inlet 21 and is evenly distributed radially. Each channel adopts a gradually changing cross-section design, with a wider inlet end to reduce flow resistance and a gradually narrowing outlet end to increase fluid velocity. The inner wall of the channel has excellent surface smoothness, which can minimize energy loss during fluid flow. Similarly, the shell phase distribution channel 24 also adopts a radially extending layout, symmetrically distributed outward from the shell phase inlet 22. The channel direction is parallel to the core phase channel, but spatially offset by a certain distance, forming a layered fluid transport. This design not only ensures the independence of the two fluids, but also creates conditions for subsequent coaxial merging.

[0039] In some embodiments, the core phase distribution channels 23 are arranged in a circumferential periodic pattern relative to the core phase inlet 21, and the shell phase distribution channels 24 are arranged in a circumferential periodic pattern relative to the shell phase inlet 22. This circumferential periodic layout 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 system 23 adopts a symmetrical radial distribution pattern with the core phase inlet 21 as the center point. Each core phase channel extends uniformly along the radial path from the central inlet, forming a perfect star-shaped array in three-dimensional space. This symmetrical layout ensures that the core phase fluid dispersed from the central point can be uniformly distributed to each outlet, avoiding flow unevenness caused by differences in channel position. Similarly, the shell phase distribution channel system 24 also follows the circumferential periodic principle, radiating outwards from the shell phase inlet 22 as the center. All shell phase channels maintain consistency in spatial angle and extension length, forming a highly ordered ring-shaped distribution network. This design ensures that the coating material can be uniformly delivered to the interface of each coaxial channel 25. The two flow channel systems are spatially coordinated, maintaining their independence while forming a synergistic relationship. The symmetrically designed flow channel system has self-balancing characteristics, automatically compensating for the effects of changes in fluid viscosity or pressure fluctuations, ensuring a high degree of consistency in fluid parameters at each outlet.

[0040] Furthermore, in this embodiment, the microsphere collecting device 30 includes an inner cavity 32, which communicates with 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 connect to the core phase inlet 21 without severe folding. Each additional device that the fluid comes into direct contact with increases the risk of contamination; the inner cavity 32 reduces contamination during the preparation process.

[0041] In some embodiments, the microsphere collecting device 30 includes a liquid level regulating chamber 33. The top of the microsphere collecting pool 31 is connected to the liquid level regulating chamber 33 through a notch 34, thereby achieving automatic and stable control of the oil phase liquid level. The connection between the microsphere collecting pool 31 and the regulating chamber adopts a transition structure design. The size of the notch 34 is calculated using fluid dynamics to ensure free flow of liquid while effectively preventing microspheres from accidentally entering the regulating chamber. In some embodiments, the width of the notch 34 is 1.5 mm to 4 mm, and the vertical distance between the bottom of the notch 34 and the top of the inner wall of the microsphere collecting pool 31 is 1.5 mm to 4 mm. In one embodiment, the change in the total volume of the microsphere collecting pool 31 will cause the total volume to increase due to the entry of microspheres into the pool. Therefore, in order to keep the liquid level in the microsphere collecting pool 31 constant, the oil phase of the microsphere volume needs to flow from the microsphere collecting pool 31 into the control pool. That is, after the liquid level rises, the excess liquid flows into the control pool through the notch 34. The control pool can be empty initially. This design eliminates the inconvenience of frequent manual adjustment of the liquid level required by traditional collecting devices and achieves long-term stable automated operation. In some embodiments, the liquid level regulating chamber 33 is equipped with a visual liquid level indicator, allowing operators to monitor the system status in real time. The chamber is made of corrosion-resistant material to prevent oil phase liquid adhesion and residue. The sealing performance of the entire system has been rigorously tested to ensure that there will be no leakage problems during long-term use.

[0042] In some embodiments, the core-shell hydrogel microsphere preparation device 10 also includes a photocuring component, which is located on the side of the microsphere collecting device 30 and features a modular design for easy installation and maintenance. The photocuring component integrates a high-performance light source system, providing specific wavelengths of ultraviolet or visible light irradiation according to the curing requirements of different hydrogel materials. The light source is professionally optically designed, combined with a precise reflective system and a light-uniforming device to ensure uniform light distribution and avoid localized excessive or insufficient light. At least a portion of the microsphere collecting device 30 is a light-transmitting structure, through which the photocuring component irradiates the microsphere collecting pool 31. Specific areas of the collecting pool are made of highly transparent material, forming a high-quality light-transmitting window. This light-transmitting structure undergoes special treatment, possessing extremely high light transmittance and excellent weather resistance, maintaining stable optical performance over a long period. 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 photocuring component irradiates the microspheres in the collecting pool from all directions through the light-transmitting structure. The light penetrates the transparent curing medium and directly acts on the hydrogel microspheres, initiating a photocrosslinking reaction in the material. This irradiation method avoids the shading effect that can occur with traditional top-down irradiation, ensuring that each microsphere receives uniform light intensity and thus achieving consistent curing results. The photocuring component not only improves the curing efficiency of the microspheres but also guarantees the integrity and stability of the core-shell structure. Through precisely controlled light conditions, the hydrogel material exhibits excellent mechanical and functional properties.

[0043] Furthermore, in this embodiment, the number of core phase distribution channels 23 and shell phase distribution channels 24 is the same, and each has any number ranging from 2 to 24. The modular design of the number of channels fully considers the process requirements of different production scales, providing users with broad application adaptability. In the standard configuration, the number of core phase distribution channels 23 and shell phase distribution channels 24 always maintains a one-to-one correspondence, ensuring that each core phase channel can obtain a matching shell phase encapsulation 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 uniformly and completely encapsulated to form microspheres with consistent structures. The lower limit of the number of channels is set to 2, which can meet the needs of laboratory research and development and small-batch pilot production. The 2-channel design reduces equipment complexity and maintenance costs while ensuring basic production efficiency, making it particularly suitable for experimental verification work in the process development stage. Each channel is optimized to ensure uniform fluid distribution even in the minimum number configuration. The upper limit of the number of channels is extended to 24, which is geared towards the needs of industrial mass production. The parallel operation mode of 24 flow channels significantly increases equipment capacity, meeting the stringent requirements of large-scale production. When multiple flow channels work together, the system employs a precise fluid balance design to ensure highly consistent flow rate and pressure across all channels, preventing product quality fluctuations caused by an increase in the number of flow channels. Within the range of 2 to 24 flow channels, users can choose intermediate configurations such as 8, 12, 16, and 20 channels based on specific production needs. Each configuration has undergone rigorous fluid dynamics verification to guarantee operational stability under different flow channel numbers. The equipment adopts a standardized interface design, and adjustments to the number of flow channels can be made through module replacement, making operation simple and quick.

[0044] In some embodiments, the microsphere collecting device 30 can control the distance from the outlet of the microspheres in the microsphere preparation device 20 to the surface of the oil phase fluid in the microsphere collecting pool 31 by controlling the height of the inner wall of the microsphere collecting pool 31, thereby controlling the diameter of the core-shell hydrogel microspheres. This allows for a simple change in the height of the support structure of the microsphere collecting pool 31, controlling the distance from the inner conical core phase outlet 253 and the outer conical shell phase outlet 254 to the surface of the microsphere collecting pool 31, and thus adjusting the overall size of the core-shell microspheres.

[0045] In one embodiment, in the core-shell hydrogel microsphere preparation device 10, a microsphere preparation device 20 made of biocompatible material is first horizontally installed above a microsphere collection device 30. An oil phase medium containing acetic acid is injected into the microsphere collection pool 31 and connected to a fluid pipeline. During preparation, the sodium alginate shell phase fluid and the core phase fluid enter their respective separatory pools. After being uniformly distributed by a symmetrically distributed flow channel system, a layered fluid is formed at the end of the coaxial flow channel 25. When the composite fluid is dripped into the oil phase from the microsphere outlet, the calcium carbonate nanoparticles in the shell layer react with acetic acid to generate calcium ions, promoting rapid cross-linking and solidification of sodium alginate to form a core-shell structure. Finally, the oil phase is removed by centrifugation, yielding uniformly dispersed core-shell hydrogel microspheres, which can be freeze-dried for easy storage and use. The entire process achieves continuous automated production from fluid distribution to microsphere solidification, ensuring good product consistency and repeatability.

[0046] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. A device for preparing core-shell hydrogel microspheres, characterized in that, include: The microsphere preparation apparatus includes a core phase inlet, a shell phase inlet, multiple core phase distribution channels communicating with the core phase inlet, and multiple shell phase distribution channels communicating with the shell phase inlet. The core phase distribution channels and the shell phase distribution channels are connected at their respective ends to form a coaxial channel. A microsphere collection device includes a microsphere collection pool disposed below the coaxial flow channel, wherein the microsphere collection pool is used to hold oil phase fluid; The nucleus fluid entering through the nucleus inlet and the shell fluid entering through the shell inlet form a stratified fluid at the coaxial flow channel and drip into the microsphere collection pool; The coaxial flow channel includes a central nucleus phase channel and an annular shell phase channel. The annular shell phase channel surrounds the outside of the central nucleus phase channel. The central nucleus phase channel is connected to the nucleus phase distribution channel, and the annular shell phase channel is connected to the shell phase distribution channel. The nucleus phase distribution channel and the shell phase distribution channel correspond one-to-one in the height direction. The nucleus phase distribution channel extends radially along the nucleus phase inlet, and the shell phase distribution channel extends radially along the shell phase inlet.

2. The equipment for preparing core-shell hydrogel microspheres according to claim 1, characterized in that, The coaxial flow channel includes an inner conical nucleus phase outlet and an outer conical shell phase outlet, wherein the outer conical shell phase outlet and the inner conical nucleus phase outlet are coaxially arranged; the end of the nucleus phase distribution flow channel is connected to the inner conical nucleus phase outlet, and the end of the shell phase distribution flow channel is connected to the outer conical shell phase outlet.

3. The apparatus for preparing core-shell hydrogel microspheres according to claim 1, characterized in that, Each of the nucleus phase distribution channels is arranged in a circumferential periodic manner relative to the nucleus phase inlet, and each of the shell phase distribution channels is arranged in a circumferential periodic manner relative to the shell phase inlet.

4. The apparatus for preparing core-shell hydrogel microspheres according to claim 1, characterized in that, The microsphere collecting device includes an inner cavity that is connected to the shell phase inlet.

5. The apparatus for preparing core-shell hydrogel microspheres according to claim 1, characterized in that, The microsphere collecting device includes a liquid level adjustment chamber, and the top of the microsphere collecting pool is connected to the liquid level adjustment chamber through a notch.

6. The apparatus for preparing core-shell hydrogel microspheres according to claim 5, characterized in that, The liquid level adjustment chamber maintains the height of the solidified medium liquid level in the microsphere collection pool by adjusting the volume of the chamber.

7. The apparatus for preparing core-shell hydrogel microspheres according to claim 1, characterized in that, It also includes a photocuring component, which is disposed on the side of the microsphere collecting device. At least a portion of the microsphere collecting device is a light-transmitting structure, and the photocuring component illuminates the microsphere collecting pool through the light-transmitting structure.

8. The apparatus for preparing core-shell hydrogel microspheres according to claim 1, characterized in that, The number of nucleus phase distribution channels and shell phase distribution channels is the same, and each has any number between 2 and 24.

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